NAMPT MODULATORS

Abstract

Provided are compounds of Formula (I):

Description

FIELD

Provided herein are alkyl carbamate compounds, pharmaceutical compositions comprising such compounds, and methods of treating various diseases and conditions mediated by nicotinamide phosphoribosyltransferase (NAMPT) with such compounds.

BACKGROUND

The present disclosure relates to the use of modulators of nicotinamide phosphoribosyltransferase (NAMPT) and derivatives thereof, as well as enhancers or inducers of NAMPT expression, NAMPT activity or NAMPT-mediated signaling for preventing or treating a variety of pathological conditions.

Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme (enzyme cofactor) involved in fundamental biological processes of both catabolic and anabolic metabolism. As a coenzyme, NAD is associated with many oxidative enzymes (typically dehydrogenases) involved in energy metabolism, serving as a universal electron carrier. NAD exists in cells in the oxidized state (NAD+ and NADP+), and the reduced state (NADH and NADPH), acting as a chemical means to capture and transfer free energy from oxidative processes in catabolism, or to provide small packets of energy to build macromolecules in anabolism. NADH produced from the oxidation of carbohydrates, lipids, and amino acids provides reducing equivalents to the electron transport chain of mitochondria, ultimately driving the synthesis of ATP in oxidative phosphorylation.

More than 200 enzymes use either NAD+ or NADP+ as a coenzyme, and the enzymatic functions are not limited to energy metabolism. It is now appreciated that NAD+ plays a role in regulating diverse functions, including mitochondrial function, respiratory capacity, and biogenesis, mitochondrial-nuclear signaling. Further, it controls cell signaling, gene expression, DNA repair, hematopoiesis, immune function, the unfolded protein response, and autophagy. Furthermore, NAD is anti-inflammatory and is the precursor for NADPH, which is the primary source of reducing power for combating oxidative stress. A large body of literature indicates that boosting NAD levels is an effective strategy to either prevent or ameliorate a wide variety of disease states (Strømland et al., Biochem Soc Trans. 2019, 47(1):119-130; Ralto et al., Nat Rev Nephrol. 2019; Fang et al., Trends Mol Med. 2017, 23(10):899-916; Yoshino et al., Cell Metab. 2011, 14(4):528-36; Yang and Sauve, Biochim Biophys Acta. 2016, 1864:1787-1800; Verdin, Science. 2015, 350(6265):1208-13).

Levels of NAD+ and NADP+-associated enzymes play important roles in normal physiology and are altered under various disease and stress conditions including aging. Cellular NAD+ levels decrease during aging, metabolic disease, inflammatory diseases, during ischemia/reperfusion injury, and in other conditions in humans (Massudi et al., PLoS ONE. 2012, 7(7): e42357) and animals (Yang et al., Cell. 2007, 130(6):1095-107; Braidy et al. PLoS One. 2011, 26; 6(4):e19194; Peek et al. Science. 2013, 342(6158):1243417; Ghosh et al., J Neurosci. 2012, 32(17):5821-32), suggesting that modulation of cellular NAD+ level affects the speed and severity of the decline and deterioration of bodily functions. Therefore, an increase in cellular NAD+ concentration could be beneficial in the context of aging and age-related diseases.

The cellular NAD+ pool is controlled by a balance between the activity of NAD+-synthesizing and consuming enzymes. In mammals, NAD+ is synthesized from a variety of dietary sources, including one or more of its major precursors that include: tryptophan (Trp), nicotinic acid (NA), nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and nicotinamide (NAM). Based upon the bioavailability of its precursors, there are three pathways for the synthesis of NAD+ in cells: (i) from Trp by the de novo biosynthesis pathway or kynurenine pathway (ii) from NA in the Preiss-Handler pathway and (iii) from NAM, NR, and NMN in the salvage pathway (Verdin et al., Science. 2015, 350(6265):1208-13). Of these, the predominant NAD+ biosynthetic pathway involves the step of synthesis of nicotinamide mononucleotide (NMN) using nicotinamide and 5′-phosphoribosyl-pyrophosphate by the rate-limiting enzyme nicotinamide phosphoribosyl-transferase (NAMPT) that is critical to determination of longevity and responses to a variety of stresses (Fulco et al, Dev Cell. 2008, 14(5):661-73; Imai, Curr Pharm Des. 2009, 15(1):20-8; Revollo et al., J Biol Chem. 2004, 279(49):50754-63; Revollo et al., Cell Metab. 2007, November; 6(5):363-75; van der Veer et al., J Biol Chem. 2007, 282(15):10841-5; Yang et al., Cell. 2007, 130(6):1095-107). Thus, increasing the rate of NAMPT catalysis by a small molecule activator would be an effective strategy to boost NAD levels and thereby address a broad spectrum of disease states. These include cardiac diseases, chemotherapy induced tissue damage, renal diseases, metabolic diseases, muscular diseases, neurological diseases and injuries, diseases caused by impaired stem cell function, DNA damage and primary mitochondrial disorders, and ocular diseases. NAMPT activators capable of CNS penetration also have the ability to boost NAD levels in the brain which is advantageous for treating CNS related diseases.

SUMMARY

In one aspect, provided herein is a compound of Formula (I):

• • or a pharmaceutically acceptable salt thereof, wherein:
  • Ring A is: i) 5- to 6-membered heteroaryl optionally substituted with 1 to 4 R^A, or

• • each R^A is independently selected from the group consisting of:
  • halogen;
  • cyano;
  • C₁-C₆ alkyl optionally substituted with 1 to 3 independently selected halogens or —OH; —O(C₁-C₆ alkyl) optionally substituted with 1 to 3 independently selected halogens; and —C(O)NR^A1R^A2, wherein R^A1 and R^A2 are each independently hydrogen or C₁-C₆ alkyl;
  • R^D is selected from the group consisting of:
  • halogen;
  • cyano;
  • C₁-C₆ alkyl optionally substituted with 1 to 3 independently selected halogens or —OH; —O(C₁-C₆ alkyl) optionally substituted with 1 to 3 independently selected halogens; and —C(O)NR^A1R^A2, wherein R^A1 and R^A2 are each independently hydrogen or C₁-C₆ alkyl;
  • L is selected from the group consisting of a bond, C₁-C₆ alkylene,
  • #—O—(C₁-C₆ alkylene)-$, #—C(O)—(C₁-C₆ alkylene)-$,
  • #—(C₁-C₆ alkylene)-C(O)—$, #—N(R^L)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-N(R^L)—$,
  • #—(C₁-C₆ alkylene)-N(R^L)—(C₁-C₆ alkylene)-$,
  • #—C(O)—N(R^L)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-C(O)—N(R^L)—$,
  • #—N(R^L)—C(O)—CH₂-$, #—(C₁-C₆ alkylene)-N(R^L)—C(O)—$,
  • #—(C₁-C₆ alkylene)-C(O)—N(R^L)—(C₁-C₆ alkylene)-$,
  • #—(C₁-C₆ alkylene)-N(R^L)—C(O)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-N(R^L)—S(O)₂-$,
  • #—N(R^L)—S(O)₂—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-S(O)₂—N(R^L)—$, #—S(O)₂—N(R^L)—(C₁-C₆ alkylene)-$, #—S(O)₂—N(R^L)—$, and #—N(C₁-C₆ alkyl)-S(O)₂-$, wherein #represents the attachment point to ring B, and $ represents the attachment point to the remainder of the molecule;
  • wherein each C₁-C₆ alkylene of L is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C₁-C₆ alkyl; and
  • wherein each R^L is independently hydrogen or C₁-C₆ alkyl;
  • Ring B is 4- to 10-membered heterocycloalkyl, 3- to 8-membered cycloalkyl, 5- to 6-membered heteroaryl, or phenyl;
  • each R^B is independently selected from the group consisting of:
  • halogen;
  • —OH;
  • oxo;
  • cyano;
  • O(C₁-C₆ alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens;
  • —C(O)(C₁-C₆ alkyl);
  • —C(O)O(C₁-C₆ alkyl);
  • phenyl;
  • 5- to 6-membered heteroaryl;
  • 4- to 8-membered heterocycloalkyl;
  • 3- to 8-membered cycloalkyl;
  • —C(O)(3- to 8-membered cycloalkyl) optionally substituted with 1 to 3 independently selected halogens;
  • —C(O)(4- to 8-membered heterocycloalkyl) optionally substituted with 1 to 3 independently selected halogens;
  • —S(O)₂(C₁-C₆ alkyl);
  • —S(O)₂(3- to 8-membered cycloalkyl);
  • —S(O)₂(4- to 8-membered heterocycloalkyl);
  • —C(O)NR^B1R^B2;
  • —S(O)₂NR^B1R^B2;
  • —NR^C1S(O)₂NR^B1R^B2;
  • —(C═N—R^C1)—NR^B1R^B2;
  • —NR^C1—(C═N—R^C1)—NR^B1R^B2;
  • —NR^C1—(C═N—CN)—NR^B1R^B2; and
  • C₁-C₆ alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of halogen, —OH, 4- to 8-membered heterocycloalkyl, and —O(C₁-C₆ alkyl);
  • wherein R^C1, R^B1 and R^B2 are each independently hydrogen or C₁-C₆ alkyl;
  • m is 0, 1, 2, 3, or 4;
  • n is 0, 1, 2, 3, 4, or 5;
  • R^C is halogen, cyano, C₁-C₆ alkyl, OH, —O(C₁-C₆ alkyl), or 3- to 8-membered cycloalkyl; and
  • p is 0, 1, 2, 3, or 4;
  • wherein:
  • a) when L is a bond, ring B is selected from the group consisting of

• • b) when ring B is pyridin-4-yl and A is phenyl, R^D is selected from the group consisting of carbamoyl, chloro, hydroxymethyl, difluoromethyl, methoxy, and cyano; and
  • c) when L is —CH₂—CH₂—, n is 0, 1, or 2.

In one aspect, provided herein is a compound of Formula (I):

• • or a pharmaceutically acceptable salt thereof, wherein:
  • Ring A is: i) 5- to 6-membered heteroaryl optionally substituted with 1 to 4 R^A, or

• • each R^A is independently selected from the group consisting of:
  • halogen;
  • cyano;
  • C₁-C₆ alkyl optionally substituted with 1 to 3 independently selected halogens or —OH;
  • —O(C₁-C₆ alkyl) optionally substituted with 1 to 3 independently selected halogens; and
  • —C(O)NR^A1R^A2, wherein R^A1 and R^A2 are each independently hydrogen or C₁-C₆ alkyl; R^D is selected from the group consisting of:
  • halogen;
  • cyano;
  • C₁-C₆ alkyl optionally substituted with 1 to 3 independently selected halogens or —OH;
  • —O(C₁-C₆ alkyl) optionally substituted with 1 to 3 independently selected halogens; and
  • —C(O)NR^A1R^A2, wherein R^A1 and R^A2 are each independently hydrogen or C₁-C₆ alkyl;
  • L is selected from the group consisting of a bond, C₁-C₆ alkylene,
  • #—O—(C₁-C₆ alkylene)-$, #—C(O)—(C₁-C₆ alkylene)-$,
  • #—(C₁-C₆ alkylene)-C(O)—$, #—N(R^L)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-N(R^L)—$,
  • #—(C₁-C₆ alkylene)-N(R^L)—(C₁-C₆ alkylene)-$,
  • #—C(O)—N(R^L)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-C(O)—N(R^L)—$,
  • #—N(R^L)—C(O)—CH₂-$, #—(C₁-C₆ alkylene)-N(R^L)—C(O)—$,
  • #—(C₁-C₆ alkylene)-C(O)—N(R^L)—(C₁-C₆ alkylene)-$,
  • #—(C₁-C₆ alkylene)-N(R^L)—C(O)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-N(R^L)—S(O)₂-$,
  • #—N(R^L)—S(O)₂—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-S(O)₂—N(R^L)—$, #—S(O)₂—N(R^L)—(C₁-C₆ alkylene)-$, #—S(O)₂—N(R^L)—$, and #—N(C₁-C₆ alkyl)-S(O)₂-$, wherein #represents the attachment point to ring B, and $ represents the attachment point to the remainder of the molecule;
  • wherein each C₁-C₆ alkylene of L is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C₁-C₆ alkyl; and
  • wherein each R^L is independently hydrogen or C₁-C₆ alkyl;
  • Ring B is 4- to 10-membered heterocycloalkyl, 3- to 8-membered cycloalkyl, 5- to 6-membered heteroaryl, or phenyl;
  • each R^B is independently selected from the group consisting of:
  • halogen;
  • —OH;
  • oxo;
  • cyano;
  • —O(C₁-C₆ alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens;
  • —C(O)(C₁-C₆ alkyl);
  • —C(O)O(C₁-C₆ alkyl);
  • phenyl;
  • 5- to 6-membered heteroaryl;
  • 4- to 8-membered heterocycloalkyl;
  • 3- to 8-membered cycloalkyl;
  • —C(O)(3- to 8-membered cycloalkyl);
  • —C(O)(4-8-membered heterocycloalkyl);
  • —S(O)₂(C₁-C₆ alkyl);
  • —S(O)₂(3- to 8-membered cycloalkyl);
  • —C(O)NR^B1R^B2;
  • —S(O)₂NR^B1R^B2;
  • —NR^C1S(O)₂NR^B1R^B2;
  • —(C═N—R^C1)—NR^B1R^B2;
  • —NR^C1—(C═N—R^C1)—NR^B1R^B2;
  • —NR^C1—(C═N—CN)—NR^B1R^B2; and
  • C₁-C₆ alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of halogen, —OH, and —O(C₁-C₆ alkyl);
  • wherein R^C1, R^B1 and R^B2 are each independently hydrogen or C₁-C₆ alkyl;
  • m is 0, 1, 2, 3, or 4;
  • n is 0, 1, 2, 3, 4, or 5;
  • R^C is halogen, cyano, C₁-C₆ alkyl, OH, —O(C₁-C₆ alkyl), or 3- to 8-membered cycloalkyl; and
  • p is 0, 1, 2, 3, or 4;
  • wherein:
  • a) when L is a bond, ring B is selected from the group consisting of

• • b) when ring B is pyridin-4-yl and A is phenyl, R^D is selected from the group consisting of carbamoyl, chloro, hydroxymethyl, difluoromethyl, methoxy, and cyano; and
  • c) when L is —CH₂—CH₂—, n is 0, 1, or 2.

In another aspect, provided is a compound of Table 1, or a pharmaceutically acceptable salt thereof.

In a further aspect, provided herein are pharmaceutical compositions comprising at least one compound of Formula (I) or of Table 1, or a pharmaceutically acceptable salt of any of the foregoing, optionally further comprising a pharmaceutically acceptable excipient.

In another aspect, provided herein is a method of treating a disease or condition mediated by NAMPT activity in a subject in need thereof, comprising administering to the subject an effective amount of at least one compound of Formula (I), such as a compound of Table 1, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising at least one compound of Formula (I). In some embodiments, the disease or condition is selected from the group consisting of cancer, a hyperproliferative disease or condition, an inflammatory disease or condition, a metabolic disorder, a cardiac disease or condition, chemotherapy induced tissue damage, a renal disease, a metabolic disease, a neurological disease or injury, a neurodegenerative disorder or disease, diseases caused by impaired stem cell function, diseases caused by DNA damage, primary mitochondrial disorders, or a muscle disease or muscle wasting disorder. In some embodiments, the disease or condition is selected from the group consisting of obesity, atherosclerosis, insulin resistance, type 2 diabetes, cardiovascular disease, Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, depression, Down syndrome, neonatal nerve injury, aging, axonal degeneration, carpal tunnel syndrome, Guillain-Barre syndrome, nerve damage, polio (poliomyelitis), and spinal cord injury.

Additional embodiments, features, and advantages of the present disclosure will be apparent from the following detailed description and through practice of the present disclosure.

For the sake of brevity, the disclosures of publications cited in this specification, including patents, are herein incorporated by reference.

DETAILED DESCRIPTION

Definitions

As used in the present specification, the following words and phrases are generally intended to have the meanings as set forth below, except to the extent that the context in which they are used indicates otherwise.

Throughout this application, unless the context indicates otherwise, references to a compound of Formula (I) includes all subgroups of Formula (I) defined herein, including all substructures, subgenera, preferences, embodiments, examples and particular compounds defined and/or described herein. References to a compound of Formula (I) and subgroups thereof include ionic forms, polymorphs, pseudopolymorphs, amorphous forms, solvates, co-crystals, chelates, isomers, tautomers, oxides (e.g., N-oxides, S-oxides), esters, prodrugs, isotopes and/or protected forms thereof. In some embodiments, references to a compound of Formula (I) and subgroups thereof include polymorphs, solvates, co-crystals, isomers, tautomers and/or oxides thereof. In some embodiments, references to a compound of Formula (I) and subgroups thereof include polymorphs, solvates, and/or co-crystals thereof. In some embodiments, references to a compound of Formula (I) and subgroups thereof include isomers, tautomers and/or oxides thereof. In some embodiments, references to a compound of Formula (I) and subgroups thereof, include solvates thereof. Similarly, the term “salts” includes solvates of salts of compounds.

“Alkyl” encompasses straight and branched carbon chains having the indicated number of carbon atoms, for example, from 1 to 20 carbon atoms, or 1 to 8 carbon atoms, or 1 to 6 carbon atoms. For example, C_1-6 alkyl encompasses both straight and branched chain alkyl of from 1 to 6 carbon atoms. When an alkyl residue having a specific number of carbons is named, all branched and straight chain versions having that number of carbons are intended to be encompassed; thus, for example, “propyl” includes n-propyl and isopropyl; and “butyl” includes n-butyl, sec-butyl, isobutyl and t-butyl. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, 2-pentyl, 3-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, and 3-methylpentyl.

As used herein, the term “alkylene” refers to divalent alkyl group as defined herein above having 1 to 20 carbon atoms. Unless otherwise provided, alkylene refers to moieties having 1 to 20 carbon atoms, 1 to 16 carbon atoms, 1 to 10 carbon atoms, 1 to 7 carbon atoms, or 1 to 4 carbon atoms. Alkylene groups include, but are not limited to, methylene, ethylene, n-propylene, iso-propylene, n-butylene, sec-butylene, iso-butylene, tert-butylene, n-pentylene, isopentylene, neopentylene, n-hexylene, 3-methylhexylene, 2,2-dimethylpentylene, 2,3-dimethylpentylene, n-heptylene, n-octylene, n-nonylene, and n-decylene.

When a range of values is given (e.g., C_1-6 alkyl), each value within the range as well as all intervening ranges are included. For example, “C_1-6 alkyl” includes C₁, C₂, C₃, C₄, C₅, C₆, C_1-6, C_2-6, C_3-6, C_4-6, C_5-6, C_1-5, C_2-5, C_3-5, C_4-5, C_1-4, C_2-4, C_3-4, C_1-3, C_2-3, and C_1-2 alkyl.

“Cycloalkyl” indicates a non-aromatic, fully saturated carbocyclic ring having the indicated number of carbon atoms, for example, 3 to 10, or 3 to 8, or 3 to 6 ring carbon atoms. Cycloalkyl groups may be monocyclic or polycyclic (e.g., bicyclic, tricyclic), spiro, branched, and/or bridged. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl, as well as bridged, caged, and spirocyclic ring groups (e.g., norbornane, bicyclo[2.2.2]octane, spiro[3.3]heptane). In addition, one ring of a polycyclic cycloalkyl group may be aromatic, provided the polycyclic cycloalkyl group is bound to the parent structure via a non-aromatic carbon. For example, a 1,2,3,4-tetrahydronaphthalen-1-yl group (wherein the moiety is bound to the parent structure via a non-aromatic carbon atom) is a cycloalkyl group, while 1,2,3,4-tetrahydronaphthalen-5-yl (wherein the moiety is bound to the parent structure via an aromatic carbon atom) is not considered a cycloalkyl group. Examples of polycyclic cycloalkyl groups consisting of a cycloalkyl group fused to an aromatic ring are described below.

“Cycloalkenyl” indicates a non-aromatic carbocyclic ring, containing the indicated number of carbon atoms (e.g., 3 to 10, or 3 to 8, or 3 to 6 ring carbon atoms) and at least one carbon-carbon double bond. Cycloalkenyl groups may be monocyclic or polycyclic (e.g., bicyclic, tricyclic). Examples of cycloalkenyl groups include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, and cyclohexenyl, as well as bridged and caged ring groups (e.g., bicyclo[2.2.2]octene). In addition, one ring of a polycyclic cycloalkenyl group may be aromatic, provided the polycyclic alkenyl group is bound to the parent structure via a non-aromatic carbon atom. For example, inden-1-yl (wherein the moiety is bound to the parent structure via a non-aromatic carbon atom) is considered a cycloalkenyl group, while inden-4-yl (wherein the moiety is bound to the parent structure via an aromatic carbon atom) is not considered a cycloalkenyl group. Examples of polycyclic cycloalkenyl groups consisting of a cycloalkenyl group fused to an aromatic ring are described below.

“Aryl” indicates an aromatic carbocyclic ring having the indicated number of carbon atoms, for example, 6 to 12 or 6 to 10 carbon atoms. Aryl groups may be monocyclic or polycyclic (e.g., bicyclic, tricyclic). In some instances, both rings of a polycyclic aryl group are aromatic (e.g., naphthyl). In other instances, polycyclic aryl groups may include a non-aromatic ring fused to an aromatic ring, provided the polycyclic aryl group is bound to the parent structure via an atom in the aromatic ring. Thus, a 1,2,3,4-tetrahydronaphthalen-5-yl group (wherein the moiety is bound to the parent structure via an aromatic carbon atom) is considered an aryl group, while 1,2,3,4-tetrahydronaphthalen-1-yl (wherein the moiety is bound to the parent structure via a non-aromatic carbon atom) is not considered an aryl group. Similarly, a 1,2,3,4-tetrahydroquinolin-8-yl group (wherein the moiety is bound to the parent structure via an aromatic carbon atom) is considered an aryl group, while 1,2,3,4-tetrahydroquinolin-1-yl group (wherein the moiety is bound to the parent structure via a non-aromatic nitrogen atom) is not considered an aryl group. However, the term “aryl” does not encompass or overlap with “heteroaryl”, as defined herein, regardless of the point of attachment (e.g., both quinolin-5-yl and quinolin-2-yl are heteroaryl groups). In some instances, aryl is phenyl or naphthyl. In certain instances, aryl is phenyl. Additional examples of aryl groups comprising an aromatic carbon ring fused to a non-aromatic ring are described below.

“Heteroaryl” indicates an aromatic ring containing the indicated number of atoms (e.g., 5 to 12, or 5 to 10 membered heteroaryl) made up of one or more heteroatoms (e.g., 1, 2, 3 or 4 heteroatoms) selected from N, O and S and with the remaining ring atoms being carbon. Heteroaryl groups do not contain adjacent S and O atoms. In some embodiments, the total number of S and O atoms in the heteroaryl group is not more than 2. In some embodiments, the total number of S and O atoms in the heteroaryl group is not more than 1. Unless otherwise indicated, heteroaryl groups may be bound to the parent structure by a carbon or nitrogen atom, as valency permits. For example, “pyridyl” includes 2-pyridyl, 3-pyridyl and 4-pyridyl groups, and “pyrrolyl” includes 1-pyrrolyl, 2-pyrrolyl and 3-pyrrolyl groups.

In some instances, a heteroaryl group is monocyclic. Examples include pyrrole, pyrazole, imidazole, triazole (e.g., 1,2,3-triazole, 1,2,4-triazole, 1,2,4-triazole), tetrazole, furan, isoxazole, oxazole, oxadiazole (e.g., 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,3,4-oxadiazole), thiophene, isothiazole, thiazole, thiadiazole (e.g., 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,3,4-thiadiazole), pyridine, pyridazine, pyrimidine, pyrazine, triazine (e.g., 1,2,4-triazine, 1,3,5-triazine) and tetrazine.

In some instances, both rings of a polycyclic heteroaryl group are aromatic. Examples include indole, isoindole, indazole, benzoimidazole, benzotriazole, benzofuran, benzoxazole, benzoisoxazole, benzoxadiazole, benzothiophene, benzothiazole, benzoisothiazole, benzothiadiazole, 1H-pyrrolo[2,3-b]pyridine, 1H-pyrazolo[3,4-b]pyridine, 3H-imidazo[4,5-b]pyridine, 3H-[1,2,3]triazolo[4,5-b]pyridine, 1H-pyrrolo[3,2-b]pyridine, 1H-pyrazolo[4,3-b]pyridine, 1H-imidazo[4,5-b]pyridine, 1H-[1,2,3]triazolo[4,5-b]pyridine, 1H-pyrrolo[2,3-c]pyridine, 1H-pyrazolo[3,4-c]pyridine, 3H-imidazo[4,5-c]pyridine, 3H-[1,2,3]triazolo[4,5-c]pyridine, 1H-pyrrolo[3,2-c]pyridine, 1H-pyrazolo[4,3-c]pyridine, 1H-imidazo[4,5-c]pyridine, 1H-[1,2,3]triazolo[4,5-c]pyridine, furo[2,3-b]pyridine, oxazolo[5,4-b]pyridine, isoxazolo[5,4-b]pyridine, [1,2,3]oxadiazolo[5,4-b]pyridine, furo[3,2-b]pyridine, oxazolo[4,5-b]pyridine, isoxazolo[4,5-b]pyridine, [1,2,3]oxadiazolo[4,5-b]pyridine, furo[2,3-c]pyridine, oxazolo[5,4-c]pyridine, isoxazolo[5,4-c]pyridine, [1,2,3]oxadiazolo[5,4-c]pyridine, furo[3,2-c]pyridine, oxazolo[4,5-c]pyridine, isoxazolo[4,5-c]pyridine, [1,2,3]oxadiazolo[4,5-c]pyridine, thieno[2,3-b]pyridine, thiazolo[5,4-b]pyridine, isothiazolo[5,4-b]pyridine, [1,2,3]thiadiazolo[5,4-b]pyridine, thieno[3,2-b]pyridine, thiazolo[4,5-b]pyridine, isothiazolo[4,5-b]pyridine, [1,2,3]thiadiazolo[4,5-b]pyridine, thieno[2,3-c]pyridine, thiazolo[5,4-c]pyridine, isothiazolo[5,4-c]pyridine, [1,2,3]thiadiazolo[5,4-c]pyridine, thieno[3,2-c]pyridine, thiazolo[4,5-c]pyridine, isothiazolo[4,5-c]pyridine, [1,2,3]thiadiazolo[4,5-c]pyridine, quinoline, isoquinoline, cinnoline, quinazoline, quinoxaline, phthalazine, naphthyridine (e.g., 1,8-naphthyridine, 1,7-naphthyridine, 1,6-naphthyridine, 1,5-naphthyridine, 2,7-naphthyridine, 2,6-naphthyridine), imidazo[1,2-a]pyridine, 1H-pyrazolo[3,4-d]thiazole, 1H-pyrazolo[4,3-d]thiazole and imidazo[2,1-b]thiazole.

In other instances, polycyclic heteroaryl groups may include a non-aromatic ring (e.g., cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl) fused to a heteroaryl ring, provided the polycyclic heteroaryl group is bound to the parent structure via an atom in the aromatic ring. For example, a 4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl group (wherein the moiety is bound to the parent structure via an aromatic carbon atom) is considered a heteroaryl group, while 4,5,6,7-tetrahydrobenzo[d]thiazol-5-yl (wherein the moiety is bound to the parent structure via a non-aromatic carbon atom) is not considered a heteroaryl group. Examples of polycyclic heteroaryl groups consisting of a heteroaryl ring fused to a non-aromatic ring are described below.

“Heterocycloalkyl” indicates a non-aromatic, fully saturated ring having the indicated number of atoms (e.g., 3 to 10, or 3 to 7, membered heterocycloalkyl) made up of one or more heteroatoms (e.g., 1, 2, 3 or 4 heteroatoms) selected from N, O and S and with the remaining ring atoms being carbon. Heterocycloalkyl groups may be monocyclic or polycyclic (e.g., bicyclic, tricyclic), spiro, branched, and/or bridged. Examples of heterocycloalkyl groups include oxiranyl, aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl. Examples include thiomorpholine S-oxide and thiomorpholine S,S-dioxide. Examples of spirocyclic heterocycloalkyl groups include azaspiro[3.3]heptane, diazaspiro[3.3]heptane, diazaspiro[3.4]octane, and diazaspiro[3.5]nonane. In addition, one ring of a polycyclic heterocycloalkyl group may be aromatic (e.g., aryl or heteroaryl), provided the polycyclic heterocycloalkyl group is bound to the parent structure via a non-aromatic carbon or nitrogen atom. For example, a 1,2,3,4-tetrahydroquinolin-1-yl group (wherein the moiety is bound to the parent structure via a non-aromatic nitrogen atom) is considered a heterocycloalkyl group, while 1,2,3,4-tetrahydroquinolin-8-yl group (wherein the moiety is bound to the parent structure via an aromatic carbon atom) is not considered a heterocycloalkyl group. Examples of polycyclic heterocycloalkyl groups consisting of a heterocycloalkyl group fused to an aromatic ring are described below.

“Heterocycloalkenyl” indicates a non-aromatic ring having the indicated number of atoms (e.g., 3 to 10, or 3 to 7, membered heterocycloalkyl) made up of one or more heteroatoms (e.g., 1, 2, 3 or 4 heteroatoms) selected from N, O and S and with the remaining ring atoms being carbon, and at least one double bond derived by the removal of one molecule of hydrogen from adjacent carbon atoms, adjacent nitrogen atoms, or adjacent carbon and nitrogen atoms of the corresponding heterocycloalkyl. Heterocycloalkenyl groups may be monocyclic or polycyclic (e.g., bicyclic, tricyclic). Examples of heterocycloalkenyl groups include dihydrofuranyl (e.g., 2,3-dihydrofuranyl, 2,5-dihydrofuranyl), dihydrothiophenyl (e.g., 2,3-dihydrothiophenyl, 2,5-dihydrothiophenyl), dihydropyrrolyl (e.g., 2,3-dihydro-1H-pyrrolyl, 2,5-dihydro-1H-pyrrolyl), dihydroimidazolyl (e.g., 2,3-dihydro-1H-imidazolyl, 4,5-dihydro-1H-imidazolyl), pyranyl, dihydropyranyl (e.g., 3,4-dihydro-2H-pyranyl, 3,6-dihydro-2H-pyranyl), tetrahydropyridinyl (e.g., 1,2,3,4-tetrahydropyridinyl, 1,2,3,6-tetrahydropyridinyl) and dihydropyridine (e.g., 1,2-dihydropyridine, 1,4-dihydropyridine). In addition, one ring of a polycyclic heterocycloalkenyl group may be aromatic (e.g., aryl or heteroaryl), provided the polycyclic heterocycloalkenyl group is bound to the parent structure via a non-aromatic carbon or nitrogen atom. For example, a 1,2-dihydroquinolin-1-yl group (wherein the moiety is bound to the parent structure via a non-aromatic nitrogen atom) is considered a heterocycloalkenyl group, while 1,2-dihydroquinolin-8-yl group (wherein the moiety is bound to the parent structure via an aromatic carbon atom) is not considered a heterocycloalkenyl group. Examples of polycyclic heterocycloalkenyl groups consisting of a heterocycloalkenyl group fused to an aromatic ring are described below.

Examples of polycyclic rings consisting of an aromatic ring (e.g., aryl or heteroaryl) fused to a non-aromatic ring (e.g., cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl) include indenyl, 2,3-dihydro-1H-indenyl, 1,2,3,4-tetrahydronaphthalenyl, benzo[1,3]dioxolyl, tetrahydroquinolinyl, 2,3-dihydrobenzo[1,4]dioxinyl, indolinyl, isoindolinyl, 2,3-dihydro-1H-indazolyl, 2,3-dihydro-1H-benzo[d]imidazolyl, 2,3-dihydrobenzofuranyl, 1,3-dihydroisobenzofuranyl, 1,3-dihydrobenzo[c]isoxazolyl, 2,3-dihydrobenzo[d]isoxazolyl, 2,3-dihydrobenzo[d]oxazolyl, 2,3-dihydrobenzo[b]thiophenyl, 1,3-dihydrobenzo[c]thiophenyl, 1,3-dihydrobenzo[c]isothiazolyl, 2,3-dihydrobenzo[d]isothiazolyl, 2,3-dihydrobenzo[d]thiazolyl, 5,6-dihydro-4H-cyclopenta[d]thiazolyl, 4,5,6,7-tetrahydrobenzo[d]thiazolyl, 5,6-dihydro-4H-pyrrolo[3,4-d]thiazolyl, 4,5,6,7-tetrahydrothiazolo[5,4-c]pyridinyl, indolin-2-one, indolin-3-one, isoindolin-1-one, 1,2-dihydroindazol-3-one, 1H-benzo[d]imidazol-2(3H)-one, benzofuran-2(3H)-one, benzofuran-3(2H)-one, isobenzofuran-1(3H)-one, benzo[c]isoxazol-3(1H)-one, benzo[d]isoxazol-3(2H)-one, benzo[d]oxazol-2(3H)-one, benzo[b]thiophen-2(3H)-one, benzo[b]thiophen-3(2H)-one, benzo[c]thiophen-1(3H)-one, benzo[c]isothiazol-3(1H)-one, benzo[d]isothiazol-3(2H)-one, benzo[d]thiazol-2(3H)-one, 4,5-dihydropyrrolo[3,4-d]thiazol-6-one, 1,2-dihydropyrazolo[3,4-d]thiazol-3-one, quinolin-4(3H)-one, quinazolin-4(3H)-one, quinazoline-2,4(1H,3H)-dione, quinoxalin-2(1H)-one, quinoxaline-2,3(1H,4H)-dione, cinnolin-4(3H)-one, pyridin-2(1H)-one, pyrimidin-2(1H)-one, pyrimidin-4(3H)-one, pyridazin-3(2H)-one, 1H-pyrrolo[3,2-b]pyridin-2(3H)-one, 1H-pyrrolo[3,2-c]pyridin-2(3H)-one, 1H-pyrrolo[2,3-c]pyridin-2(3H)-one, 1H-pyrrolo[2,3-b]pyridin-2(3H)-one, 1,2-dihydropyrazolo[3,4-d]thiazol-3-one and 4,5-dihydropyrrolo[3,4-d]thiazol-6-one. As discussed herein, whether each ring is considered an aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl group is determined by the atom through which the moiety is bound to the parent structure.

“Halogen” or “halo” refers to fluorine, chlorine, bromine or iodine.

Unless otherwise indicated, compounds disclosed and/or described herein include all possible enantiomers, diastereomers, meso isomers and other stereoisomeric forms, including racemic mixtures, optically pure forms and intermediate mixtures thereof. Enantiomers, diastereomers, meso isomers and other stereoisomeric forms can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. Unless specified otherwise, when the compounds disclosed and/or described herein contain olefinic double bonds or other centers of geometric asymmetry, it is intended that the compounds include both E and Z isomers. When the compounds described herein contain moieties capable of tautomerization, and unless specified otherwise, it is intended that the compounds include all possible tautomers.

“Protecting group” has the meaning conventionally associated with it in organic synthesis, i.e., a group that selectively blocks one or more reactive sites in a multifunctional compound such that a chemical reaction can be carried out selectively on another unprotected reactive site, and such that the group can readily be removed after the selective reaction is complete. A variety of protecting groups are disclosed, for example, in T.H. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, Third Edition, John Wiley & Sons, New York (1999). For example, a “hydroxy protected form” contains at least one hydroxy group protected with a hydroxy protecting group. Likewise, amines and other reactive groups may similarly be protected.

The term “pharmaceutically acceptable salt” refers to a salt of any of the compounds herein which are known to be non-toxic and are commonly used in the pharmaceutical literature. In some embodiments, the pharmaceutically acceptable salt of a compound retains the biological effectiveness of the compounds described herein and are not biologically or otherwise undesirable. Examples of pharmaceutically acceptable salts can be found in Berge et al., Pharmaceutical Salts, J. Pharmaceutical Sciences, January 1977, 66(1), 1-19. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, lactic acid, oxalic acid, malic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 2-hydroxyethylsulfonic acid, p-toluenesulfonic acid, stearic acid and salicylic acid. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, and aluminum. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines; substituted amines including naturally occurring substituted amines; cyclic amines; and basic ion exchange resins. Examples of organic bases include isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. In some embodiments, the pharmaceutically acceptable base addition salt is selected from ammonium, potassium, sodium, calcium, and magnesium salts.

If the compound described herein is obtained as an acid addition salt, the free base can be obtained by basifying a solution of the acid salt. Conversely, if the compound is a free base, an addition salt, particularly a pharmaceutically acceptable addition salt, may be produced by dissolving the free base in a suitable organic solvent and treating the solution with an acid, in accordance with conventional procedures for preparing acid addition salts from base compounds (see, e.g., Berge et al., Pharmaceutical Salts, J. Pharmaceutical Sciences, January 1977, 66(1), 1-19). Those skilled in the art will recognize various synthetic methodologies that may be used to prepare pharmaceutically acceptable addition salts.

A “solvate” is formed by the interaction of a solvent and a compound. Suitable solvents include, for example, water and alcohols (e.g., ethanol). Solvates include hydrates having any ratio of compound to water, such as monohydrates, dihydrates and hemi-hydrates.

The term “substituted” means that the specified group or moiety bears one or more substituents including, but not limited to, substituents such as alkoxy, acyl, acyloxy, carbonylalkoxy, acylamino, amino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, cycloalkyl, cycloalkenyl, aryl, heteroaryl, aryloxy, cyano, azido, halo, hydroxyl, nitro, carboxyl, thiol, thioalkyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, alkynyl, heterocycloalkyl, heterocycloalkenyl, aralkyl, aminosulfonyl, sulfonylamino, sulfonyl, oxo, carbonylalkylenealkoxy and the like. The term “unsubstituted” means that the specified group bears no substituents. Where the term “substituted” is used to describe a structural system, the substitution is meant to occur at any valency-allowed position on the system, including at valency-allowed positions that are heteroatomic. For example, an “optionally substituted piperazin-2-yl” group can be substituted at any valency-allowed position, including nitrogen.

When a group with variable substitution is depicted, such as

the indicated substituent can be at any valency-allowed position, including the —NH—, as in

Furthermore, when a bicyclic group with variable substitution is depicted, the indicated substituent can be at any valency-allowed position at either ring or at both rings. For instance, the R^B substituent of

can be at either the cyclopentyl or the cyclopropyl component of the fused system, or it can be at both the cyclopentyl and the cyclopropyl components of the fused system. When a group or moiety bears more than one substituent, it is understood that the substituents may be the same or different from one another. In some embodiments, a substituted group or moiety bears from one to five substituents. In some embodiments, a substituted group or moiety bears one substituent. In some embodiments, a substituted group or moiety bears two substituents. In some embodiments, a substituted group or moiety bears three substituents. In some embodiments, a substituted group or moiety bears four substituents. In some embodiments, a substituted group or moiety bears five substituents.

By “optional” or “optionally” is meant that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event or circumstance occurs and instances in which it does not. For example, “optionally substituted alkyl” encompasses both “alkyl” and “substituted alkyl” as defined herein. It will be understood by those skilled in the art, with respect to any group containing one or more substituents, that such groups are not intended to introduce any substitution or substitution patterns that are sterically impractical, synthetically non-feasible, and/or inherently unstable. It will also be understood that where a group or moiety is optionally substituted, the disclosure includes both embodiments in which the group or moiety is substituted and embodiments in which the group or moiety is unsubstituted.

The compounds disclosed and/or described herein can be enriched isotopic forms, e.g., enriched in the content of ²H, ³H, ¹¹C, ¹³C and/or ¹⁴C. In one embodiment, the compound contains at least one deuterium atom. Such deuterated forms can be made, for example, by the procedure described in U.S. Pat. Nos. 5,846,514 and 6,334,997. Such deuterated compounds may improve the efficacy and increase the duration of action of compounds disclosed and/or described herein. Deuterium substituted compounds can be synthesized using various methods, such as those described in: Dean, D., Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development, Curr. Pharm. Des., 2000; 6(10); Kabalka, G. et al., The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E., Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

The term “pharmaceutically acceptable carrier” or “pharmaceutically acceptable excipient” includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents and the like. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, its use in pharmaceutical compositions is contemplated. Supplementary active ingredients can also be incorporated into the pharmaceutical compositions.

The terms “patient,” “individual,” and “subject” refer to an animal, such as a mammal, bird, or fish. In some embodiments, the patient or subject is a mammal. Mammals include, for example, mice, rats, dogs, cats, pigs, sheep, horses, cows and humans. In some embodiments, the patient or subject is a human, for example a human that has been or will be the object of treatment, observation or experiment. The compounds, compositions and methods described herein can be useful in both human therapy and veterinary applications.

As used herein, the term “therapeutic” refers to the ability to modulate nicotinamide phosphoribosyltransferase (NAMPT). As used herein, “modulation” refers to a change in activity as a direct or indirect response to the presence of a chemical entity as described herein, relative to the activity of in the absence of the chemical entity. The change may be an increase in activity or a decrease in activity, and may be due to the direct interaction of the chemical entity with the target or due to the interaction of the chemical entity with one or more other factors that in turn affect the target's activity. For example, the presence of the chemical entity may, for example, increase or decrease the target activity by directly binding to the target, by causing (directly or indirectly) another factor to increase or decrease the target activity, or by (directly or indirectly) increasing or decreasing the amount of target present in the cell or organism.

The term “therapeutically effective amount” or “effective amount” refers to that amount of a compound disclosed and/or described herein that is sufficient to affect treatment, as defined herein, when administered to a patient in need of such treatment. A therapeutically effective amount of a compound may be an amount sufficient to treat a disease responsive to modulation of nicotinamide phosphoribosyltransferase (NAMPT). The therapeutically effective amount will vary depending upon, for example, the subject and disease condition being treated, the weight and age of the subject, the severity of the disease condition, the particular compound, the dosing regimen to be followed, timing of administration, the manner of administration, all of which can readily be determined by one of ordinary skill in the art. The therapeutically effective amount may be ascertained experimentally, for example by assaying blood concentration of the chemical entity, or theoretically, by calculating bioavailability.

“Treatment” (and related terms, such as “treat”, “treated”, “treating”) includes one or more of: slowing or arresting the development of clinical symptoms of a disease or disorder; and/or relieving a disease or disorder (i.e., causing relief from or regression of clinical symptoms). The term covers both complete and partial reduction or prevention of the condition or disorder, and complete or partial reduction of clinical symptoms of a disease or disorder. Thus, compounds described and/or disclosed herein may prevent an existing disease or disorder from worsening, assist in the management of the disease or disorder, or reduce or eliminate the disease or disorder.

Compounds

Compounds and salts thereof (such as pharmaceutically acceptable salts) are detailed herein, including in the Brief Summary and in the appended claims. Also provided are the use of all of the compounds described herein, including any and all stereoisomers, including geometric isomers (cis/trans), E/Z isomers, enantiomers, diastereomers, and mixtures thereof in any ratio including racemic mixtures, salts and solvates of the compounds described herein, as well as methods of making such compounds. Any compound described herein may also be referred to as a drug.

In one aspect, provided herein is a compound of Formula (I):

• • or a pharmaceutically acceptable salt thereof, wherein:
  • Ring A is: i) 5- to 6-membered heteroaryl optionally substituted with 1 to 4 R^A, or

• • each R^A is independently selected from the group consisting of:
  • halogen;
  • cyano;
  • C₁-C₆ alkyl optionally substituted with 1 to 3 independently selected halogens or —OH;
  • —O(C₁-C₆ alkyl) optionally substituted with 1 to 3 independently selected halogens; and
  • —C(O)NR^A1R^A2, wherein R^A1 and R^A2 are each independently hydrogen or C₁-C₆ alkyl;
  • R^D is selected from the group consisting of:
  • halogen;
  • cyano; C₁-C₆ alkyl optionally substituted with 1 to 3 independently selected halogens or —OH;
  • —O(C₁-C₆ alkyl) optionally substituted with 1 to 3 independently selected halogens; and
  • —C(O)NR^A1R^A2, wherein R^A1 and R^A2 are each independently hydrogen or C₁-C₆ alkyl;
  • L is selected from the group consisting of a bond, C₁-C₆ alkylene,
  • #—O—(C₁-C₆ alkylene)-$, #—C(O)—(C₁-C₆ alkylene)-$,
  • #—(C₁-C₆ alkylene)-C(O)—$, #—N(R^L)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-N(R^L)—$,
  • #—(C₁-C₆ alkylene)-N(R^L)—(C₁-C₆ alkylene)-$,
  • #—C(O)—N(R^L)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-C(O)—N(R^L)—$,
  • #—N(R^L)—C(O)—CH₂-$, #—(C₁-C₆ alkylene)-N(R^L)—C(O)—$,
  • #—(C₁-C₆ alkylene)-C(O)—N(R^L)—(C₁-C₆ alkylene)-$,
  • #—(C₁-C₆ alkylene)-N(R^L)—C(O)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-N(R^L)—S(O)₂-$,
  • #—N(R^L)—S(O)₂—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-S(O)₂—N(R^L)—$, #—S(O)₂—N(R^L)—(C₁-C₆ alkylene)-$, #—S(O)₂—N(R^L)—$, and #—N(C₁-C₆ alkyl)-S(O)₂-$, wherein #represents the attachment point to ring B, and $ represents the attachment point to the remainder of the molecule;
  • wherein each C₁-C₆ alkylene of L is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C₁-C₆ alkyl; and
  • wherein each R^L is independently hydrogen or C₁-C₆ alkyl;
  • Ring B is 4- to 10-membered heterocycloalkyl, 3- to 8-membered cycloalkyl, 5- to 6-membered heteroaryl, or phenyl;
  • each R^B is independently selected from the group consisting of:
  • halogen;
  • —OH;
  • oxo;
  • cyano;
  • —O(C₁-C₆ alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens;
  • —C(O)(C₁-C₆ alkyl);
  • —C(O)O(C₁-C₆ alkyl);
  • phenyl;
  • 5- to 6-membered heteroaryl;
  • 4- to 8-membered heterocycloalkyl;
  • 3- to 8-membered cycloalkyl;
  • —C(O)(3- to 8-membered cycloalkyl) optionally substituted with 1 to 3 independently selected halogens;
  • —C(O)(4- to 8-membered heterocycloalkyl) optionally substituted with 1 to 3 independently selected halogens;
  • —S(O)₂(C₁-C₆ alkyl);
  • —S(O)₂(3- to 8-membered cycloalkyl);
  • —S(O)₂(4- to 8-membered heterocycloalkyl);
  • —C(O)NR^B1R^B2;
  • —S(O)₂NR^B1R^B2;
  • —NR^C1S(O)₂NR^B1R^B2;
  • —(C═N—R^C1)—NR^B1R^B2;
  • —NR^C1—(C═N—R^C1)—NR^B1R^B2;
  • —NR^C1—(C═N—CN)—NR^B1R^B2; and
  • C₁-C₆ alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of halogen, —OH, 4- to 8-membered heterocycloalkyl, and —O(C₁-C₆ alkyl);
  • wherein R^C1, R^B1 and R^B2 are each independently hydrogen or C₁-C₆ alkyl;
  • m is 0, 1, 2, 3, or 4;
  • n is 0, 1, 2, 3, 4, or 5;
  • R^C is halogen, cyano, C₁-C₆ alkyl, OH, —O(C₁-C₆ alkyl), or 3- to 8-membered cycloalkyl; and
  • p is 0, 1, 2, 3, or 4;
  • wherein:
  • a) when L is a bond, ring B is selected from the group consisting of

• • b) when ring B is pyridin-4-yl and A is phenyl, R^D is selected from the group consisting of carbamoyl, chloro, hydroxymethyl, difluoromethyl, methoxy, and cyano; and
  • c) when L is —CH₂—CH₂—, n is 0, 1, or 2.

In one aspect, provided herein is a compound of Formula (I):

• • or a pharmaceutically acceptable salt thereof, wherein:
  • Ring A is: i) 5- to 6-membered heteroaryl optionally substituted with 1 to 4 R^A, or

• • each R^A is independently selected from the group consisting of:
  • halogen;
  • cyano;
  • C₁-C₆ alkyl optionally substituted with 1 to 3 independently selected halogens or —OH;
  • —O(C₁-C₆ alkyl) optionally substituted with 1 to 3 independently selected halogens; and
  • —C(O)NR^A1R^A2, wherein R^A1 and R^A2 are each independently hydrogen or C₁-C₆ alkyl;
  • R^D is selected from the group consisting of:
  • halogen;
  • cyano;
  • C₁-C₆ alkyl optionally substituted with 1 to 3 independently selected halogens or —OH;
  • —O(C₁-C₆ alkyl) optionally substituted with 1 to 3 independently selected halogens; and
  • —C(O)NR^A1R^A2, wherein R^A1 and R^A2 are each independently hydrogen or C₁-C₆ alkyl;
  • L is selected from the group consisting of a bond, C₁-C₆ alkylene,
  • #—O—(C₁-C₆ alkylene)-$, #—C(O)—(C₁-C₆ alkylene)-$,
  • #—(C₁-C₆ alkylene)-C(O)—$, #—N(R^L)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-N(R^L)—$,
  • #—(C₁-C₆ alkylene)-N(R^L)—(C₁-C₆ alkylene)-$,
  • #—C(O)—N(R^L)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-C(O)—N(R^L)—$,
  • #—N(R^L)—C(O)—CH₂-$, #—(C₁-C₆ alkylene)-N(R^L)—C(O)—$,
  • #—(C₁-C₆ alkylene)-C(O)—N(R^L)—(C₁-C₆ alkylene)-$,
  • #—(C₁-C₆ alkylene)-N(R^L)—C(O)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-N(R^L)—S(O)₂-$,
  • #—N(R^L)—S(O)₂—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-S(O)₂—N(R^L)—$, #—S(O)₂—N(R^L)—(C₁-C₆ alkylene)-$, #—S(O)₂—N(R^L)—$, and #—N(C₁-C₆ alkyl)-S(O)₂-$, wherein #represents the attachment point to ring B, and $ represents the attachment point to the remainder of the molecule;
  • wherein each C₁-C₆ alkylene of L is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C₁-C₆ alkyl; and
  • wherein each R^L is independently hydrogen or C₁-C₆ alkyl;
  • Ring B is 4- to 10-membered heterocycloalkyl, 3- to 8-membered cycloalkyl, 5- to 6-membered heteroaryl, or phenyl;
  • each R^B is independently selected from the group consisting of:
  • halogen;
  • —OH;
  • oxo;
  • cyano;
  • —O(C₁-C₆ alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens;
  • —C(O)(C₁-C₆ alkyl);
  • —C(O)O(C₁-C₆ alkyl);
  • phenyl;
  • 5- to 6-membered heteroaryl;
  • 4- to 8-membered heterocycloalkyl;
  • 3- to 8-membered cycloalkyl;
  • —C(O)(3- to 8-membered cycloalkyl);
  • —C(O)(4-8-membered heterocycloalkyl);
  • —S(O)₂(C₁-C₆ alkyl);
  • —S(O)₂(3- to 8-membered cycloalkyl);
  • —C(O)NR^B1R^B2;
  • —S(O)₂NR^B1R^B2;
  • —NR^C1S(O)₂NR^B1R^B2;
  • —(C═N—R^C1)—NR^B1R^B2;
  • —NR^C1—(C═N—R^C1)—NR^B1R^B2;
  • —NR^C1—(C═N—CN)—NR^B1R^B2; and
  • C₁-C₆ alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of halogen, —OH, and —O(C₁-C₆ alkyl);
  • wherein R^C1, R^B1 and R^B2 are each independently hydrogen or C₁-C₆ alkyl;
  • m is 0, 1, 2, 3, or 4;
  • n is 0, 1, 2, 3, 4, or 5;
  • R^C is halogen, cyano, C₁-C₆ alkyl, OH, —O(C₁-C₆ alkyl), or 3- to 8-membered cycloalkyl; and
  • p is 0, 1, 2, 3, or 4;
  • wherein:
  • a) when L is a bond, ring B is selected from the group consisting of

• • b) when ring B is pyridin-4-yl and A is phenyl, R^D is selected from the group consisting of carbamoyl, chloro, hydroxymethyl, difluoromethyl, methoxy, and cyano; and
  • c) when L is —CH₂—CH₂—, n is 0, 1, or 2.

In some embodiments of a compound of Formula (I), Ring A is 5- to 6-membered heteroaryl optionally substituted with 1 to 4 R^A, or Ring A is

In some embodiments, Ring A is 5- to 6-membered heteroaryl optionally substituted with 1 to 4 R^A. In some embodiments, Ring A is

In some embodiments of a compound of Formula (I), Ring A is

In some embodiments, R^D is halogen or —O(C₁-C₆ alkyl) optionally substituted with 1 to 3 independently selected halogens. In some embodiments, R^D is halogen. In some embodiments, R^D is halogen; cyano; C₁-C₆ alkyl optionally substituted with 1 to 3 independently selected halogens or —OH; —O(C₁-C₆ alkyl) optionally substituted with 1 to 3 independently selected halogens; or —C(O)NR^A1R^A2, wherein R^A1 and R^A2 are each independently hydrogen or C₁-C₆ alkyl. In some embodiments, R^D is halogen; cyano; C₁-C₃ alkyl optionally substituted with 1 to 3 independently selected halogens or —OH; —O(C₁-C₃ alkyl) optionally substituted with 1 to 3 independently selected halogens; or —C(O)NR^A1R^A2, wherein R^A1 and R^A2 are each independently hydrogen or C₁-C₃ alkyl. In some embodiments, R^D is chloro or fluoro; cyano; methyl optionally substituted with 1 to 3 independently selected chloro, fluoro, or —OH substituents; —OCH₃ optionally substituted with 1 to 3 independently selected chloro or fluoro substituents; or —C(O)NR^A1R^A2, wherein R^A1 and R^A2 are each independently hydrogen or methyl. In some embodiments, R^D is chloro or fluoro; cyano; —CH₃; methyl substituted with 1 to 3 independently selected fluoro or —OH substituents; —OCH₃ optionally substituted with 1 to 3 fluoro substituents; or —C(O)NH₂. In some embodiments, R^D is chloro or fluoro; cyano; —CH₃; —CH₂OH; —CHF₂; —OCH₃; —OCHF₂; or —C(O)NH₂. In some embodiments, R^D is chloro. In some embodiments, R^D is fluoro. In some embodiments, R^D is cyano. In some embodiments, R^D is —CH₂OH. In some embodiments, R^D is —CH₃. In some embodiments, R^D is —CH₂OH. In some embodiments, R^D is —CHF₂. In some embodiments, R^D is —OCH₃. In some embodiments, R^D is —OCHF₂. In some embodiments, R^D is —C(O)NH₂.

In some embodiments of a compound of Formula (I), Ring A is

and R^A is halogen. In some embodiments, Ring A is

In some embodiments, Ring A is

and R^A is halogen. In some embodiments, Ring A is

In some embodiments of a compound of Formula (I), Ring A, R^A, and R^D are taken together to form a moiety selected from the group consisting of:

In some embodiments of a compound of Formula (I), Ring A, R^A, and R^D are taken together to form

In some embodiments of a compound of Formula (I), Ring A, R^A, and R^D are taken together to form

In some embodiments of a compound of Formula (I), Ring A, R^A, and R^D are taken together to form

In some embodiments of a compound of Formula (I), Ring A, R^A, and R^D are taken together to form

In some embodiments of a compound of Formula (I), Ring A, R^A, and R^D are taken together to form

In some embodiments of a compound of Formula (I), Ring A, R^A, and R^D are taken together to form

In some embodiments of a compound of Formula (I), Ring A, R^A, and R^D are taken together to form

In some embodiments of a compound of Formula (I), Ring A, R^A, and R^D are taken together to form

In some embodiments of a compound of Formula (I), Ring A, R^A and R^D are taken together to form

In some embodiments of a compound of Formula (I), Ring A is 5- to 6-membered heteroaryl optionally substituted with 1 to 4 R^A.

In some embodiments of a compound of Formula (I), Ring A is 5-membered heteroaryl optionally substituted with 1 to 4 R^A. In some embodiments, Ring A is oxazolyl, pyrazolyl, thiazolyl, isothiazolyl, or isoxazolyl, each of which is optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is oxazolyl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is oxazolyl optionally substituted with 1 to 2 R^A. In some embodiments, Ring A is pyrazolyl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is thiazolyl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is thiazolyl optionally substituted with 1 to 2 R^A. In some embodiments, Ring A is isothiazolyl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is isoxazolyl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is 1H-pyrazol-4-yl, isothiazol-4-yl, isothiazol-5-yl, isoxazol-4-yl, oxazol-5-yl, or thiazol-5-yl, each of which is optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is 1H-pyrazol-4-yl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is isothiazol-4-yl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is isothiazol-5-yl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is isoxazol-4-yl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is oxazol-5-yl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is oxazol-5-yl optionally substituted with 1 to 2 R^A. In some embodiments, Ring A is thiazol-5-yl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is thiazol-5-yl optionally substituted with 1 to 2 R^A.

In some embodiments of a compound of Formula (I), Ring A is 5-membered heteroaryl optionally substituted with 1 to 4 R^A. In some embodiments, Ring A is oxazolyl, pyrazolyl, thiazolyl, isothiazolyl, or isoxazolyl, each of which is optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is oxazolyl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is oxazolyl optionally substituted with 1 to 2 R^A. In some embodiments, Ring A is pyrazolyl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is thiazolyl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is isothiazolyl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is isoxazolyl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is 1H-pyrazol-4-yl, isothiazol-4-yl, isothiazol-5-yl, isoxazol-4-yl, oxazol-5-yl, or thiazol-5-yl, each of which is optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is 1H-pyrazol-4-yl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is isothiazol-4-yl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is isothiazol-5-yl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is isoxazol-4-yl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is oxazol-5-yl optionally substituted with 1 to 3 R^A. In some embodiments, Ring A is oxazol-5-yl optionally substituted with 1 to 2 R^A. In some embodiments, Ring A is thiazol-5-yl optionally substituted with 1 to 3 R^A.

In some embodiments of a compound of Formula (I), Ring A is unsubstituted 5-membered heteroaryl. In some embodiments, Ring A is oxazolyl, pyrazolyl, thiazolyl, isothiazolyl, or isoxazolyl, each of which is unsubstituted.

In some embodiments of a compound of Formula (I), Ring A is 6-membered heteroaryl optionally substituted with 1 to 4 R^A. In some embodiments, Ring A is pyridinyl, pyridazinyl, or pyrimidinyl, each of which is optionally substituted with 1 to 4 R^A. In some embodiments, Ring A is pyridazinyl optionally substituted with 1 to 4 R^A. In some embodiments, Ring A is pyridinyl optionally substituted with 1 to 4 R^A. In some embodiments, Ring A is pyrimidinyl optionally substituted with 1 to 4 R^A. In some embodiments, Ring A is pyridazin-4-yl, pyridin-4-yl, or pyrimidin-4-yl, each of which is optionally substituted with 1 to 4 R^A. In some embodiments, Ring A is pyridazin-4-yl, optionally substituted with 1 to 4 R^A. In some embodiments, Ring A is pyridin-4-yl, optionally substituted with 1 to 4 R^A. In some embodiments, Ring A is pyrimidin-4-yl, optionally substituted with 1 to 4 R^A.

In some embodiments of a compound of Formula (I), R^A is halogen or C₁-C₆ alkyl optionally substituted with 1 to 3 independently selected halogens. In some embodiments, R^A is halogen or C₁-C₆ alkyl. In some embodiments, R^A is halogen. In some embodiments, R^A is halogen; cyano; C₁-C₆ alkyl optionally substituted with 1 to 3 independently selected halogens or —OH; —O(C₁-C₆ alkyl) optionally substituted with 1 to 3 independently selected halogens; or —C(O)NR^A1R^A2, wherein R^A1 and R^A2 are each independently hydrogen or C₁-C₆ alkyl. In some embodiments, R^A is halogen; cyano; C₁-C₃ alkyl optionally substituted with 1 to 3 independently selected halogens or —OH; —O(C₁-C₃ alkyl) optionally substituted with 1 to 3 independently selected halogens; or —C(O)NR^A1R^A2, wherein R^A1 and R^A2 are each independently hydrogen or C₁-C₃ alkyl. In some embodiments, R^A is chloro or fluoro; cyano; methyl optionally substituted with 1 to 3 independently selected chloro, fluoro, or —OH substituents; —OCH₃ optionally substituted with 1 to 3 independently selected chloro or fluoro substituents; or —C(O)NR^A1R^A2 wherein R^A1 and R^A2 are each independently hydrogen or methyl. In some embodiments, R^A is chloro or fluoro; cyano; —CH₃; methyl substituted with 1 to 3 independently selected fluoro or —OH substituents; —OCH₃ optionally substituted with 1 to 3 fluoro substituents; or —C(O)NH₂. In some embodiments, R^A is chloro or fluoro; cyano; —CH₃; —CH₂OH; —CHF₂; —OCH₃; —OCHF₂; or —C(O)NH₂. In some embodiments, R^A is chloro. In some embodiments, R^A is fluoro. In some embodiments, R^A is cyano. In some embodiments, R^A is —CH₂OH. In some embodiments, R^A is —CH₃. In some embodiments, R^A is —CH₂OH. In some embodiments, R^A is —CHF₂. In some embodiments, R^A is —OCH₃. In some embodiments, R^A is —OCHF₂. In some embodiments, R^A is —C(O)NH₂.

In some embodiments, R^A1 and R^A1 are each independently hydrogen or C₁-C₆ alkyl. In some embodiments, R^A1 and R^A1 are each hydrogen. In some embodiments, R^A1 and R^A1 are each C₁-C₆ alkyl. In some embodiments, R^A1 is hydrogen. In some embodiments, R^A1 is C₁-C₆ alkyl. In some embodiments, R^A1 is hydrogen. In some embodiments, R^A1 is C₁-C₆ alkyl.

In some embodiments of a compound of Formula (I), Ring A and R^A are taken together to form a moiety selected from the group consisting of:

In some embodiments of a compound of Formula (I), Ring A and R^A are taken together to form

In some embodiments of a compound of Formula (I), Ring A and R^A are taken together to form

In some embodiments of a compound of Formula (I), Ring A and R^A are taken together to form

In some embodiments of a compound of Formula (I), Ring A and R^A are taken together to form

In some embodiments of a compound of Formula (I), Ring A and R^A are taken together to form

In some embodiments of a compound of Formula (I), Ring A and R^A are taken together to form

In some embodiments of a compound of Formula (I), Ring A and R^A are taken together to form

In some embodiments of a compound of Formula (I), Ring A and R^A are taken together to form

In some embodiments of a compound of Formula (I), Ring A and R^A are taken together to form

In some embodiments of a compound of Formula (I), Ring A and R^A are taken together to form

In some embodiments of a compound of Formula (I), Ring B is 4- to 10-membered heterocycloalkyl, 3- to 8-membered cycloalkyl, 5- to 6-membered heteroaryl, or phenyl. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl, 3- to 8-membered cycloalkyl, or 5- to 6-membered heteroaryl. In some embodiments of a compound of Formula (I), Ring B is 4- to 8-membered heterocycloalkyl, 3- to 8-membered cycloalkyl, 5- to 6-membered heteroaryl, or phenyl. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl, 3- to 8-membered cycloalkyl, or 5- to 6-membered heteroaryl. In some embodiments, Ring B is 4- to 10-membered heterocycloalkyl. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl. In some embodiments, Ring B is 3- to 8-membered cycloalkyl. In some embodiments, Ring B is 5- to 6-membered heteroaryl. In some embodiments, Ring B is monocyclic. In some embodiments, ring B is polycyclic. In some embodiments, Ring B is spirocyclic. In some embodiments, Ring B is a bridged bicycle. In some embodiments, Ring B is a fused bicycle.

In some embodiments of a compound of Formula (I), Ring B is pyridinyl, piperazinyl, morpholinyl, piperidinyl, pyrrolidinyl, oxazolyl, or pyrazolyl. In some embodiments, Ring B is pyridinyl, piperazinyl, morpholinyl, piperidinyl, or pyrrolidinyl. In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments of a compound of Formula (I), Ring B is selected from the group consisting of: bicyclo[3.1.0]hexanyl; [3.3]heptanyl; 1,2,4-oxadiazolyl; 1,3,4-oxadiazolyl; pyrazolyl; pyrrolyl; 2,5-diazabicyclo[4.1.0]heptanyl; 2-azabicyclo[3.1.0]hexanyl; 3-azabicyclo[3.1.0]hexanyl; 5-azaspiro[2.4]heptanyl; 8-oxa-3-azabicyclo[3.2.1]octanyl; 2-azaspiro[3.3]heptanyl; 6-azaspiro[3.4]octanyl; 8-azabicyclo[3.2.1]octanyl; 4-azaspiro[2.5]octanyl; 3-azabicyclo[3.2.1]octanyl; 3-azabicyclo[3.1.1]heptanyl; 2-azabicyclo[4.1.0]heptanyl; azetidinyl; cyclobutyl; cyclohexyl; cyclopentyl; cyclopropyl; isothiazolyl; isoxazolyl; morpholinyl; oxazolyl; oxazolidinyl; oxetanyl; phenyl; piperazinyl; piperidinyl; pyrazinyl; pyridazinyl; pyridinyl; pyrimidinyl; pyrrolidinyl; tetrahydro-2H-pyranyl; tetrahydro-2H-thiopyranyl; tetrahydrofuranyl; and thiazolyl. In some embodiments, Ring B is bicyclo[3.1.0]hexanyl. In some embodiments, Ring B is [3.3]heptanyl. In some embodiments, Ring B is 2-azaspiro[3.3]heptanyl. In some embodiments, Ring B is 6-azaspiro[3.4]octanyl. In some embodiments, Ring B is 8-azabicyclo[3.2.1]octanyl. In some embodiments, Ring B is 4-azaspiro[2.5]octanyl. In some embodiments, Ring B is 3-azabicyclo[3.2.1]octanyl. In some embodiments, Ring B is 3-azabicyclo[3.1.1]heptanyl. In some embodiments, Ring B is 2-azabicyclo[4.1.0]heptanyl. In some embodiments, Ring B is 1,2,4-oxadiazolyl. In some embodiments, Ring B is 1,3,4-oxadiazolyl. In some embodiments, Ring B is pyrazolyl. In some embodiments, Ring B is pyrrolyl. In some embodiments, Ring B is 2,5-diazabicyclo[4.1.0]heptanyl. In some embodiments, Ring B is 2-azabicyclo[3.1.0]hexanyl. In some embodiments, Ring B is 3-azabicyclo[3.1.0]hexanyl. In some embodiments, Ring B is 5-azaspiro[2.4]heptanyl. In some embodiments, Ring B is 8-oxa-3-azabicyclo[3.2.1]octanyl. In some embodiments, Ring B is azetidinyl. In some embodiments, Ring B is cyclobutyl. In some embodiments, Ring B is cyclohexyl. In some embodiments, Ring B is cyclopentyl. In some embodiments, Ring B is cyclopropyl. In some embodiments, Ring B is isothiazolyl. In some embodiments, Ring B is isoxazolyl. In some embodiments, Ring B is morpholinyl. In some embodiments, Ring B is oxazolyl. In some embodiments, Ring B is oxazolidinyl. In some embodiments, Ring B is oxetanyl. In some embodiments, Ring B is phenyl. In some embodiments, Ring B is piperazinyl. In some embodiments, Ring B is piperidinyl. In some embodiments, Ring B is pyrazinyl. In some embodiments, Ring B is pyridazinyl. In some embodiments, Ring B is pyridinyl. In some embodiments, Ring B is pyrimidinyl. In some embodiments, Ring B is pyrrolidinyl. In some embodiments, Ring B is tetrahydro-2H-pyranyl. In some embodiments, Ring B is tetrahydro-2H-thiopyranyl. In some embodiments, Ring B is tetrahydrofuranyl. In some embodiments, Ring B is thiazolyl.

In some embodiments of a compound of Formula (I), Ring B is selected from the group consisting of: bicyclo[3.1.0]hexanyl; [3.3]heptanyl; 1,2,4-oxadiazolyl; 1,3,4-oxadiazolyl; pyrazolyl; pyrrolyl; 2,5-diazabicyclo[4.1.0]heptanyl; 2-azabicyclo[3.1.0]hexanyl; 3-azabicyclo[3.1.0]hexanyl; 5-azaspiro[2.4]heptanyl; 8-oxa-3-azabicyclo[3.2.1]octanyl; azetidinyl; cyclobutyl; cyclohexyl; cyclopentyl; cyclopropyl; isothiazolyl; isoxazolyl; morpholinyl; oxazolyl; oxazolidinyl; oxetanyl; phenyl; piperazinyl; piperidinyl; pyrazinyl; pyridazinyl; pyridinyl; pyrimidinyl; pyrrolidinyl; tetrahydro-2H-pyranyl; tetrahydro-2H-thiopyranyl; tetrahydrofuranyl; and thiazolyl. In some embodiments, Ring B is bicyclo[3.1.0]hexanyl. In some embodiments, Ring B is [3.3]heptanyl. In some embodiments, Ring B is 1,2,4-oxadiazolyl. In some embodiments, Ring B is 1,3,4-oxadiazolyl. In some embodiments, Ring B is pyrazolyl. In some embodiments, Ring B is pyrrolyl. In some embodiments, Ring B is 2,5-diazabicyclo[4.1.0]heptanyl. In some embodiments, Ring B is 2-azabicyclo[3.1.0]hexanyl. In some embodiments, Ring B is 3-azabicyclo[3.1.0]hexanyl. In some embodiments, Ring B is 5-azaspiro[2.4]heptanyl. In some embodiments, Ring B is 8-oxa-3-azabicyclo[3.2.1]octanyl. In some embodiments, Ring B is azetidinyl. In some embodiments, Ring B is cyclobutyl. In some embodiments, Ring B is cyclohexyl. In some embodiments, Ring B is cyclopentyl. In some embodiments, Ring B is cyclopropyl. In some embodiments, Ring B is isothiazolyl. In some embodiments, Ring B is isoxazolyl. In some embodiments, Ring B is morpholinyl. In some embodiments, Ring B is oxazolyl. In some embodiments, Ring B is oxazolidinyl. In some embodiments, Ring B is oxetanyl. In some embodiments, Ring B is phenyl. In some embodiments, Ring B is piperazinyl. In some embodiments, Ring B is piperidinyl. In some embodiments, Ring B is pyrazinyl. In some embodiments, Ring B is pyridazinyl. In some embodiments, Ring B is pyridinyl. In some embodiments, Ring B is pyrimidinyl. In some embodiments, Ring B is pyrrolidinyl. In some embodiments, Ring B is tetrahydro-2H-pyranyl. In some embodiments, Ring B is tetrahydro-2H-thiopyranyl. In some embodiments, Ring B is tetrahydrofuranyl. In some embodiments, Ring B is thiazolyl.

In some embodiments of a compound of Formula (I), Ring B is selected from the group consisting of:

In some embodiments of a compound of Formula (I), Ring B is selected from the group consisting of:

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments, Ring B is

In some embodiments of a compound of Formula (I), each R^B is independently selected from the group consisting of halogen; —OH; oxo; cyano; —O(C₁-C₆ alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens; —C(O)(C₁-C₆ alkyl);

• • —C(O)O(C₁-C₆ alkyl); phenyl; 5- to 6-membered heteroaryl; 4- to 8-membered heterocycloalkyl;
  • 3- to 8-membered cycloalkyl; —C(O)(3- to 8-membered cycloalkyl);
  • —C(O)(4-8-membered heterocycloalkyl); —S(O)₂(C₁-C₆ alkyl); —S(O)₂(3- to 8-membered cycloalkyl); —C(O)NR^B1R^B2; —S(O)₂NR^B1R^B2; —NR^C1S(O)₂NR^B1R^B2; —(C═N—R^C1)—NR^B1R^B2;
  • NR^C1—(C═N—R^C1)—NR^B1R^B2; —NR^C1—(C═N—CN)—NR^B1R^B2; and C₁-C₆ alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of halogen, —OH, and —O(C₁-C₆ alkyl); wherein R^B1 and R^B2 are each independently hydrogen or C₁-C₆ alkyl.

In some embodiments of a compound of Formula (I), each R^B is independently selected from the group consisting of halogen; oxo; —O(C₁-C₆ alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens; C₁-C₆ alkyl optionally substituted with 1 to 5 substituents independently selected from halogen, —OH, 4- to 8-membered heterocycloalkyl, and —O(C₁-C₆ alkyl); —S(O)₂(C₁-C₆ alkyl); —S(O)₂(4- to 8-membered heterocycloalkyl); —S(O)₂(3- to 8-membered cycloalkyl); —S(O)₂NR^B1R^B2; —C(O)NR^B1R^B2; —C(O)(C₁-C₆ alkyl); —C(O)O(C₁-C₆ alkyl); —C(O)(3- to 8-membered cycloalkyl) optionally substituted with 1 to 3 independently selected halogens; —C(O)(4- to 8-membered heterocycloalkyl) optionally substituted with 1 to 3 independently selected halogens; 4- to 8-membered heterocycloalkyl; and 5- to 6-membered heteroaryl. In some embodiments of a compound of Formula (I), each R^B is independently selected from the group consisting of halogen; oxo; —O(C₁-C₆ alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens; C₁-C₆ alkyl optionally substituted with 1 to 5 substituents independently selected from halogen, —OH, and —O(C₁-C₆ alkyl); —S(O)₂(C₁-C₆ alkyl); —S(O)₂NR^B1R^B2; —C(O)NR^B1R^B2; —C(O)(C₁-C₆ alkyl); 4- to 8-membered heterocycloalkyl; and 5- to 6-membered heteroaryl. In some embodiments of a compound of Formula (I), each R^B is independently selected from the group consisting of —O(C₁-C₄ alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens; and C₁-C₄ alkyl optionally substituted with 1 to 5 substituents independently selected from halogen, —OH, 4- to 8-membered heterocycloalkyl, and —O(C₁-C₄ alkyl). In some embodiments, each R^B is independently selected from the group consisting of chloro, fluoro, or bromo; oxo; unsubstituted —O(C₁-C₃ alkyl); —O(C₁-C₃ alkyl) substituted with phenyl; —O(C₁-C₃ alkyl) substituted with 1 to 3 fluoro; —S(O)₂(C₁-C₃ alkyl); —S(O)₂NR^B1R^B2; unsubstituted C₁-C₃ alkyl; C₁-C₃ alkyl substituted with 1 to 5 substituents independently selected from chloro, fluoro, —OH, and —O(C₁-C₃ alkyl); —C(O)NH₂; C(O)NMe₂; —C(O)(C₁-C₃ alkyl); 4- to 6-membered heterocycloalkyl; and 6-membered heteroaryl. In some embodiments, each R^B is independently selected from the group consisting of chloro; fluoro; oxo; —OCH₃ optionally substituted with 1 to 3 fluoro; —CH₃; —C(O)NH₂; C(O)NMe₂; —C(O)(C₁-C₃ alkyl); 4- to 6-membered heterocycloalkyl; and 6-membered heteroaryl. In some embodiments, each R^B is independently selected from the group consisting of oxo, —C(O)(C₁-C₆ alkyl), —C(O)NR^B1R^B2, —S(O)₂(C₁-C₆ alkyl), —S(O)₂NR^B1R^B2, unsubstituted C₁-C₆ alkyl, 4- to 8-membered heterocycloalkyl, and 5- to 6-membered heteroaryl. In some embodiments, each R^B is independently selected from the group consisting of oxo, —C(O)(C₁-C₃ alkyl), —C(O)N(Me)₂, —C(O)(4- to 8-membered heterocycloalkyl) optionally substituted with 1 to 3 independently selected halogens, —C(O)(3- to 8-membered cycloalkyl) optionally substituted with 1 to 3 independently selected halogens; —S(O)₂(C₁-C₃ alkyl), —S(O)₂N(Me)₂, —C(O)O(C₁-C₄ alkyl), —S(O)₂(4- to 8-membered heterocycloalkyl), —S(O)₂(3- to 4-membered cycloalkyl), methyl, oxetanyl, and pyridinyl. In some embodiments, each R^B is independently selected from the group consisting of oxo, —C(O)(C₁-C₃ alkyl), —C(O)N(Me)₂, —S(O)₂Me, —S(O)₂N(Me)₂, methyl, oxetanyl, and pyridinyl. In some embodiments, R^B is oxo. In some embodiments, R^B is —S(O)₂NR^B1R^B2. In some embodiments, R^B is —S(O)₂(C₁-C₃ alkyl). In some embodiments, R^B is —S(O)₂(4- to 6-membered heterocycloalkyl). In some embodiments, R^B is —C(O)O(C₁-C₃ alkyl). In some embodiments, R^B is —C(O)(C₁-C₃ alkyl). In some embodiments, R^B is —C(O)(C₃ alkyl). In some embodiments, R^B is —C(O)(C₂ alkyl). In some embodiments, R^B is —C(O)(Me). In some embodiments, R^B is —C(O)N(Me)₂. In some embodiments, R^B is methyl. In some embodiments, R^B is oxetanyl. In some embodiments, R^B is pyridinyl. In some embodiments, R^B is —S(O)₂N(Me)₂. In some embodiments, R^B is —S(O)₂Et. In some embodiments, R^B is —S(O)₂Me.

In some embodiments of a compound of Formula (I), each R^B is independently selected from the group consisting of halogen; oxo; —O(C₁-C₆ alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens; C₁-C₆ alkyl optionally substituted with 1 to 5 substituents independently selected from halogen, —OH, and —O(C₁-C₆ alkyl); —S(O)₂(C₁-C₆ alkyl); —S(O)₂NR^B1R^B2; —C(O)NR^B1R^B2; —C(O)(C₁-C₆ alkyl); 4- to 8-membered heterocycloalkyl; and 5- to 6-membered heteroaryl. In some embodiments of a compound of Formula (I), each R^B is independently selected from the group consisting of halogen; oxo; —O(C₁-C₆ alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens; C₁-C₆alkyl optionally substituted with 1 to 5 substituents independently selected from halogen, —OH, and —O(C₁-C₆ alkyl); —S(O)₂(C₁-C₆ alkyl); —S(O)₂NR^B1R^B2; —C(O)NR^B1R^B2; —C(O)(C₁-C₆ alkyl); 4- to 8-membered heterocycloalkyl; and 5- to 6-membered heteroaryl. In some embodiments, each R^B is independently selected from the group consisting of chloro, fluoro, or bromo; oxo; unsubstituted —O(C₁-C₃ alkyl); —O(C₁-C₃ alkyl) substituted with phenyl; —O(C₁-C₃ alkyl) substituted with 1 to 3 fluoro; —S(O)₂(C₁-C₃ alkyl); —S(O)₂NR^B1R^B2; unsubstituted C₁-C₃ alkyl; C₁-C₃ alkyl substituted with 1 to 5 substituents independently selected from chloro, fluoro, —OH, and —O(C₁-C₃ alkyl);

• • —C(O)NH₂; C(O)NMe₂; —C(O)(C₁-C₃ alkyl); 4- to 6-membered heterocycloalkyl; and 6-membered heteroaryl. In some embodiments, each R^B is independently selected from the group consisting of chloro; fluoro; oxo; —OCH₃ optionally substituted with 1 to 3 fluoro; —CH₃; —C(O)NH₂; C(O)NMe₂; —C(O)(C₁-C₃ alkyl); 4- to 6-membered heterocycloalkyl; and 6-membered heteroaryl. In some embodiments, each R^B is independently selected from the group consisting of oxo, —C(O)(C₁-C₆ alkyl), —C(O)NR^B1R^B2, —S(O)₂(C₁-C₆ alkyl), —S(O)₂NR^B1R^B2, unsubstituted C₁-C₆ alkyl, 4- to 8-membered heterocycloalkyl, and 5- to 6-membered heteroaryl. In some embodiments, each R^B is independently selected from the group consisting of oxo, —C(O)(C₁-C₃ alkyl), —C(O)N(Me)₂, —S(O)₂Me, —S(O)₂N(Me)₂, methyl, oxetanyl, and pyridinyl. In some embodiments, R^B is oxo. In some embodiments, R^B is-S(O)₂NR^B1R^B2. In some embodiments, R^B is —S(O)₂(C₁-C₃ alkyl). In some embodiments, R^B is —C(O)(C₁-C₃ alkyl). In some embodiments, R^B is —C(O)N(Me)₂. In some embodiments, R^B is methyl. In some embodiments, R^B is oxetanyl. In some embodiments, R^B is pyridinyl. In some embodiments, R^B is —S(O)₂N(Me)₂. In some embodiments, R^B is —S(O)₂Me.

In some embodiments, R^B1 and R^B2 are each independently hydrogen or C₁-C₆ alkyl. In some embodiments, R^B1 and R^B2 are each hydrogen. In some embodiments, R^B1 and R^B2 are each C₁-C₆ alkyl. In some embodiments, R^B1 is hydrogen. In some embodiments, R^B1 is C₁-C₆ alkyl. In some embodiments, R^B2 is hydrogen. In some embodiments, R^B2 is C₁-C₆ alkyl.

In some embodiments, R^C1 is hydrogen or C₁-C₆ alkyl. In some embodiments, R^C1 is hydrogen. In some embodiments, R^C1 is C₁-C₆ alkyl. In some embodiments, R^C1 is methyl. In some embodiments, R^C1 is ethyl.

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form a moiety selected from the group consisting of:

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form a moiety selected from the group consisting of:

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

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In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

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In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

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In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

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In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

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In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

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In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

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In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

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In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

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In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

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In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

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In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), Ring B and R^B are taken together to form

In some embodiments of a compound of Formula (I), L is selected from the group consisting of a bond, C₁-C₆ alkylene, #—O—(C₁-C₆ alkylene)-$, #—C(O)—(C₁-C₆ alkylene)-$,

• • #—(C₁-C₆ alkylene)-C(O)—$, #—N(R^L)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-N(R^L)—$,
  • #—(C₁-C₆ alkylene)-N(R^L)—(C₁-C₆ alkylene)-$, #—C(O)—N(R^L)—(C₁-C₆ alkylene)-$,
  • #—(C₁-C₆ alkylene)-C(O)—N(R^L)—$, #—N(R^L)—C(O)—CH₂-$, #—(C₁-C₆ alkylene)-N(R^L)—C(O)—$,
  • #—(C₁-C₆ alkylene)-C(O)—N(R^L)—(C₁-C₆ alkylene)-$,
  • #—(C₁-C₆ alkylene)-N(R^L)—C(O)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-N(R^L)—S(O)₂-$,
  • #—N(R^L)—S(O)₂—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-S(O)₂—N(R^L)—$,
  • #—S(O)₂—N(R^L)—(C₁-C₆ alkylene)-$, #—S(O)₂—N(R^L)—$, and #—N(C₁-C₆ alkyl)-S(O)₂-$, wherein #represents the attachment point to ring B, and $ represents the attachment point to the remainder of the molecule; wherein each C₁-C₆ alkylene of L is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C₁-C₆ alkyl; and wherein each R^L is independently hydrogen or C₁-C₆ alkyl.

In some embodiments, L is selected from the group consisting of a bond, C₁-C₃ alkylene, #—O—(C₁-C₃ alkylene)-$, #—C(O)—(C₁-C₃ alkylene)-$,

• • #—(C₁-C₃ alkylene)-C(O)—$, #—N(R^L)—(C₁-C₃ alkylene)-$, #—(C₁-C₃ alkylene)-N(R^L)—$,
  • #—(C₁-C₃ alkylene)-N(R^L)—(C₁-C₃ alkylene)-$, #—C(O)—N(R^L)—(C₁-C₃ alkylene)-$,
  • #—(C₁-C₃ alkylene)-C(O)—N(R^L)—$, #—N(R^L)—C(O)—CH₂-$, #—(C₁-C₃ alkylene)-N(R^L)—C(O)—$,
  • #—(C₁-C₃ alkylene)-C(O)—N(R^L)—(C₁-C₃ alkylene)-$,
  • #—(C₁-C₃ alkylene)-N(R^L)—C(O)—(C₁-C₃ alkylene)-$, #—(C₁-C₃ alkylene)-N(R^L)—S(O)₂-$,
  • #—N(R^L)—S(O)₂—(C₁-C₃ alkylene)-$, #—(C₁-C₃ alkylene)-S(O)₂—N(R^L)—$,
  • #—S(O)₂—N(R^L)—(C₁-C₃ alkylene)-$, #—S(O)₂—N(R^L)—$, and #—N(C₁-C₃ alkyl)-S(O)₂-$, wherein #represents the attachment point to ring B, and $ represents the attachment point to the remainder of the molecule; wherein each C₁-C₃ alkylene of L is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C₁-C₃ alkyl; and wherein each R^L is independently hydrogen or C₁-C₃ alkyl.

In some embodiments, L is selected from the group consisting of a bond, C₁-C₆ alkylene, #—C(O)—N(R^L)—(C₁-C₆ alkylene)-$, #—C(O)—(C₁-C₆ alkylene)-$, and #—(C₁-C₆ alkylene)-C(O)—N(R^L)—(C₁-C₆ alkylene)-$, wherein #represents the attachment point to ring B, and $ represents the attachment point to the remainder of the molecule; wherein each C₁-C₆ alkylene of L is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C₁-C₆ alkyl; and wherein each R^L is independently hydrogen or C₁-C₆ alkyl.

In some embodiments, L is a bond, C₁-C₃ alkylene, #—C(O)—N(R^L)—(C₁-C₃ alkylene)-$, #—C(O)—(C₁-C₃ alkylene)-$, or #—(C₁-C₃ alkylene)-C(O)—N(R^L)—(C₁-C₃ alkylene)-$, wherein #represents the attachment point to ring B, and $ represents the attachment point to the remainder of the molecule; wherein each C₁-C₃ alkylene of L is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C₁-C₃ alkyl; and wherein each R^L is independently hydrogen or C₁-C₃ alkyl.

In some embodiments, each C₁-C₆ alkylene of L is substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C₁-C₆ alkyl. In some embodiments, each C₁-C₆ alkylene of L is substituted with 1 to 3 substituents independently selected from the group consisting of halogen and C₁-C₆ alkyl. In some embodiments, each C₁-C₆alkylene of L is substituted with 1 to 3 substituents independently selected from the group consisting of fluoro and methyl. In some embodiments, each C₁-C₆ alkylene of L is unsubstituted.

In some embodiments, L is a bond, C₁-C₃ alkylene, or #—C(O)—N(R^L)—(C₁-C₃ alkylene)-$, wherein #represents the attachment point to ring B, and $ represents the attachment point to the remainder of the molecule; wherein each C₁-C₆ alkylene of L is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C₁-C₆ alkyl; and wherein each R^L is independently hydrogen or C₁-C₆ alkyl. In some embodiments, L is a bond, —CH₂—, —CH₂CH₂—, or

In some embodiments, L is selected from the group consisting of a bond, #—(CO)CF₂-$, #C(O)CH(CH₃)-$, #C(O)CH₂-$, #—C(O)—N(CH₃)CH(CH₃)-$, #—C(O)—N(CH₃)CH₂-$, #—C(O)N(H)CH(CH₃)-$, #—C(O)N(H)CH₂-$, #—CH₂C(O)N(H)CH(CH₃)-$,

• • #—CH₂C(O)N(H)CH₂-$, #—CH₂N(CH₃)SO₂-$, #—CH₂N(H)C(O)CH₂-$, #—CH₂SO₂N(H)-$,
  • #—N(CH₂CH₃)SO₂-$, #—N(CH₃)SO₂-$, #—N(CH₃)C(O)CH₂-$, #—N(H)C(O)CH₂-$,
  • #—N(H)CH₂-$, #—OCH₂-$, #—S(O)₂N(H)CH₂-$, #—C(CH₃)(OH)-$, ethylene, methylene, and
  • #—S(O)₂-$. In some embodiments, L is a bond. In some embodiments, L is #—(CO)CF₂-$. In some embodiments, L is #C(O)CH(CH₃)-$. In some embodiments, L is #C(O)CH₂-$. In some embodiments, L is #—C(O)—N(CH₃)CH(CH₃)-$. In some embodiments, L is #—C(O)—N(CH₃)CH₂-$. In some embodiments, L is #—C(O)N(H)CH(CH₃)-$. In some embodiments, L is #—C(O)N(H)CH₂-$. In some embodiments, L is #—CH₂C(O)N(H)CH(CH₃)-$. In some embodiments, L is #—CH₂C(O)N(H)CH₂-$. In some embodiments, L is #—CH₂N(CH₃)SO₂-$. In some embodiments, L is #—CH₂N(H)C(O)CH₂-$. In some embodiments, L is #—CH₂SO₂N(H)-$. In some embodiments, L is #—N(CH₂CH₃)SO₂-$. In some embodiments, L is #—N(CH₃)SO₂-$. In some embodiments, L is #—N(CH₃)C(O)CH₂-$. In some embodiments, L is #—N(H)C(O)CH₂-$. In some embodiments, L is #—N(H)CH₂-$. In some embodiments, L is #—OCH₂-$. In some embodiments, L is #—S(O)₂N(H)CH₂-$. In some embodiments, L is #—C(CH₃)(OH)-$. In some embodiments, L is ethylene. In some embodiments, L is methylene. In some embodiments, L is #—S(O)₂-$.

In some embodiments of a compound of Formula (I), m is 0, 1, 2, 3, or 4. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4.

In some embodiments of a compound of Formula (I), n is 0, 1, 2, 3, 4, or 5. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5.

In some embodiments of a compound of Formula (I), p is 0, 1, 2, 3, or 4. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments, p is 4.

In some embodiments of a compound of Formula (I), p is 0, m is 0, and n is 0, 1, or 2.

In some embodiments of a compound of Formula (I), R^C is halogen, cyano, C₁-C₆ alkyl, or 3- to 8-membered cycloalkyl. In some embodiments, R^C is halogen. In some embodiments, R^C is fluoro, chloro, or bromo. In some embodiments, R^C is fluoro. In some embodiments, R^C is chloro. In some embodiments, R^C is bromo. In some embodiments, R^C is cyano. In some embodiments, R^C is C₁-C₆ alkyl. In some embodiments, R^C is methyl. In some embodiments, R^C is ethyl. In some embodiments, R^C is propyl. In some embodiments, R^C is cyclopropyl. In some embodiments, R^C is cyclobutyl. In some embodiments, R^C is cyclopentyl. In some embodiments, R^C is cyclohexyl. In some embodiments, R^C is cyclopentyl. In some embodiments, R^C is cyclooctyl.

In some embodiments of a compound of Formula (I):

• • a) when L is a bond, ring B is selected from the group consisting of

• • b) when ring B is pyridin-4-yl and A is phenyl, R^D is selected from the group consisting of carbamoyl, chloro, hydroxymethyl, difluoromethyl, methoxy, and cyano; and
  • c) when L is —CH₂—CH₂—, n is 0, 1, or 2.

In some embodiments of a compound of Formula (I), each R^B is independently selected from the group consisting of: halogen; —OH; oxo; cyano; —O(C₁-C₆ alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens;

• • —C(O)(C₁-C₃ alkyl); —C(O)O(C₁-C₆ alkyl); phenyl; 5- to 6-membered heteroaryl; 4- to 8-membered heterocycloalkyl; 3- to 8-membered cycloalkyl; —C(O)(3- to 8-membered cycloalkyl);
  • —C(O)(4-8-membered heterocycloalkyl); —S(O)₂(C₁-C₆ alkyl); —S(O)₂(3- to 8-membered cycloalkyl); —C(O)NR^B1R^B2; —S(O)₂NR^B1R^B2; —NR^C1S(O)₂NR^B1R^B2;
  • —(C═N—R^C1)—NR^B1R^B2; —NR^C1—(C═N—R^C)—NR^B1R^B2; —NR^C1—(C═N—CN)—NR^B1R^B2; and C₁-C₆ alkyl optionally substituted with 1 to 5 substituents independently selected from halogen, —OH, and —O(C₁-C₆ alkyl); wherein R^B1 and R^B2 are each independently hydrogen or C₁-C₆ alkyl.

In some embodiments of a compound of Formula (I):

• • a) when L is a bond, ring B is selected from the group consisting of

• • b) when ring B is pyridin-4-yl and A is phenyl, R^D is selected from the group consisting of carbamoyl, chloro, hydroxymethyl, difluoromethyl, methoxy, and cyano; and
  • c) when L is —CH₂—CH₂—, n is 0, 1, or 2.

In some embodiments of a compound of Formula (I), each R^B is independently selected from the group consisting of: halogen; —OH; oxo; cyano; —O(C₁-C₆ alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens;

• • —C(O)(C₁-C₃ alkyl); —C(O)O(C₁-C₆ alkyl); phenyl; 5- to 6-membered heteroaryl; 4- to 8-membered heterocycloalkyl; 3- to 8-membered cycloalkyl; —C(O)(3- to 8-membered cycloalkyl);
  • —C(O)(4-8-membered heterocycloalkyl); —S(O)₂(C₁-C₆ alkyl); —S(O)₂(3- to 8-membered cycloalkyl); —C(O)NR^B1R^B2; —S(O)₂NR^B1R^B2; —NR^C1S(O)₂NR^B1R^B2;
  • —(C═N—R^C1)—NR^B1R^B2; —NR^C1—(C═N—R^C)—NR^B1R^B2; —NR^C1—(C═N—CN)—NR^B1R^B2; and C₁-C₆ alkyl optionally substituted with 1 to 5 substituents independently selected from halogen, —OH, and —O(C₁-C₆ alkyl); wherein R^B1 and R^B2 are each independently hydrogen or C₁-C₆ alkyl.

In some embodiments of a compound of Formula (I), Ring B is 4- to 8-membered heterocycloalkyl and R^B is 5- to 6-membered heteroaryl. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is —S(O)₂(C₁-C₆ alkyl). In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is —S(O)₂(C₁-C₃ alkyl). In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is —S(O)₂(Me). In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is-S(O)₂NR^B1R^B2. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is —S(O)₂NMe₂. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is —C(O)(C₁-C₆ alkyl). In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is —C(O)(C₁-C₃ alkyl). In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is —C(O)Me. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is —C(O)NR^B1R^B2. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is 4- to 8-membered heterocycloalkyl. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is oxetanyl. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and L is #—C(O)—N(R^L)—(C₁-C₆ alkylene)-$. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and L is C₁-C₆ alkylene. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and L is a bond. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and n is 0. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl, n is 2, one R^B is C₁-C₆ alkyl, and the other R^B is oxo. In some embodiments, Ring B is 5- to 6-membered heteroaryl and R^B is C₁-C₆ alkyl. In some embodiments, Ring B is 5- to 6-membered heteroaryl and R^B is methyl. In some embodiments, Ring B is 5- to 6-membered heteroaryl and L is #—C(O)—N(R^L)—(C₁-C₆ alkylene)-$. In some embodiments, Ring B is 5- to 6-membered heteroaryl and L is C₁-C₆ alkylene. In some embodiments, Ring A is phenyl and R^D is chloro. In some embodiments, Ring A is 5- to 6-membered heteroaryl and m is 0. In some embodiments, Ring A is thiazolyl and m is 0. In some embodiments, Ring A is oxazolyl and m is 0. In some embodiments, Ring A is thiazol-5-yl and m is 0. In some embodiments, Ring A is oxazol-5-yl and m is 0.

In some embodiments of a compound of Formula (I), Ring B is 4- to 8-membered heterocycloalkyl and R^B is 5- to 6-membered heteroaryl. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is —S(O)₂(C₁-C₆ alkyl). In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is —S(O)₂(C₁-C₃ alkyl). In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is-S(O)₂NR^B1R^B2. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is —C(O)(C₁-C₆ alkyl). In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is —C(O)(C₁-C₃ alkyl). In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is —C(O)NR^B1R^B2. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and R^B is 4- to 8-membered heterocycloalkyl. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and L is #—C(O)—N(R^L)—(C₁-C₆ alkylene)-$. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and L is C₁-C₆ alkylene. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and L is a bond. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl and n is 0. In some embodiments, Ring B is 4- to 8-membered heterocycloalkyl, n is 2, one R^B is C₁-C₆ alkyl, and the other R^B is oxo. In some embodiments, Ring B is 5- to 6-membered heteroaryl and R^B is C₁-C₆ alkyl. In some embodiments, Ring B is 5- to 6-membered heteroaryl and R^B is methyl. In some embodiments, Ring B is 5- to 6-membered heteroaryl and L is #—C(O)—N(R^L)—(C₁-C₆ alkylene)-$. In some embodiments, Ring B is 5- to 6-membered heteroaryl and L is C₁-C₆ alkylene. In some embodiments, Ring A is phenyl and R^D is chloro. In some embodiments, Ring A is 5- to 6-membered heteroaryl and m is 0. In some embodiments, Ring A is thiazolyl and m is 0. In some embodiments, Ring A is oxazolyl and m is 0. In some embodiments, Ring A is thiazol-5-yl and m is 0. In some embodiments, Ring A is oxazol-5-yl and m is 0.

In some embodiments, the compound of Formula (I) is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

or a pharmaceutically acceptable salt thereof.

In some embodiments, provided herein are compounds, and salts thereof or pharmaceutically acceptable salts thereof, described in Table 1.

TABLE 1
No.	Structure	Name
1		4-methoxybenzyl (R)-(4- ((2-(pyridin-3- yl)pyrrolidin-1- yl)methyl)phenyl)carbamate
2		4-carbamoylbenzyl (R)- (4-((2-(pyridin-3- yl)pyrrolidin-1- yl)methyl)phenyl)carbamate
3		pyridin-4-ylmethyl (R)- (4-((2-(pyridin-3- yl)pyrrolidin-1- yl)methyl)phenyl)carbamate
4		oxazol-5-ylmethyl (4-(1- (dimethylcarbamoyl)piperidin-4- yl)phenyl)carbamate
5		4-(hydroxymethyl)benzyl (R)-(4-((2-(pyridin-3- yl)pyrrolidin-1- yl)methyl)phenyl)carbamate
6		oxazol-5-ylmethyl (R)- (4-((2-(pyridin-3- yl)pyrrolidin-1- yl)methyl)phenyl)carbamate
7		oxazol-5-ylmethyl (4-(1- isobutyrylpiperidin-4- yl)phenyl)carbamate
8		oxazol-5-ylmethyl (4-(1- acetylpiperidin-4- yl)phenyl)carbamate
9		(1H-pyrazol-4-yl)methyl (4-((6-methyl- nicotinamido)meth- yl)phenyl)carbamate
10		oxazol-5-ylmethyl (4-((1-(N- methylsulfamoyl)piperidin-4- yl)methyl)phenyl)carbamate
11		methyl 4-(4-(((oxazol-5- ylmethoxy)carbonyl)ami- no)benzyl)piperidine-1- carboxylate
12		4-chlorobenzyl (S)-(4-(1- (1,3,4-trimethyl-1H- pyrazole-5-carboxamido)eth- yl)phenyl)carbamate
13		oxazol-5-ylmethyl (4-(2- (1-(oxetane-3- carbonyl)piperidin-4- yl)ethyl)phenyl)carbamate
14		4-carbamoylbenzyl (4- (pyridin-4- ylmethyl)phenyl)carbamate
15		4-chlorobenzyl (4-(1- acetylpiperidin-4- yl)phenyl)carbamate
16		4-chlorobenzyl (4-(((1- acetylazetidin-3- yl)oxy)methyl)phenyl)carbamate
17		4-chlorobenzyl (4-((1-(N- methylsulfamoyl)piperidin-4- yl)methyl)phenyl)carbamate
18		oxazol-5-ylmethyl (4-((1- (methylsulfonyl)piperidin-4- yl)methyl)phenyl)carbamate
19		4-chlorobenzyl (4- ((1,3,4-trimethyl-1H- pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
20		4-chlorobenzyl (S)-(4-(1- (1-(tetrahydro-2H-pyran- 4-yl)-1H-pyrazole-5- carboxamido)eth- yl)phenyl)carbamate
21		4-chlorobenzyl (4-((6- methylnicotinamido)meth- yl)phenyl)carbamate
22		oxazol-5-ylmethyl (S)- (4-(1-(6,6- difluorospiro[3.3]heptane-2- carboxamido)eth- yl)phenyl)carbamate
23		methyl 4-(4-(((pyridin-4- ylmethoxy)carbonyl)ami- no)benzyl)piperidine-1- carboxylate
24		4-chlorobenzyl (4-((4- (pyrazin-2-yl)piperazin-1- yl)methyl)phenyl)carbamate
25		oxazol-5-ylmethyl (4-((6- methylnicotinamido)meth- yl)phenyl)carbamate
26		oxazol-5-ylmethyl (4-(2- (1-acetylpiperidin-4- yl)ethyl)phenyl)carbamate
27		oxazol-5-ylmethyl (4-((1- (N,N- dimethylsulfamoyl)piperidin-4- yl)methyl)phenyl)carbamate
28		4-chlorobenzyl (4-((4- methyl-2-oxopiperazin-1- yl)methyl)phenyl)carbamate
29		4-chlorobenzyl (4-((4- (pyridin-2-yl)piperazin-1- yl)methyl)phenyl)carbamate
30		oxazol-5-ylmethyl (4-((1- (dimethylcarbamoyl)piperidin-4- yl)methyl)phenyl)carbamate
31		oxazol-5-ylmethyl (4-((1- acetylpiperidin-4- yl)methyl)phenyl)carbamate
32		oxazol-5-ylmethyl (4-(2-(1- (dimethylcarbamoyl)piperidin-4- yl)ethyl)phenyl)carbamate
33		4-chlorobenzyl (4- ((phenylmethyl)sul- fonamido)phenyl)carbamate
34		4-chlorobenzyl (4-((1- (N,N- dimethylsulfamoyl)piperidin-4- yl)methyl)phenyl)carbamate
35		oxazol-5-ylmethyl (4-((1- isobutyrylpiperidin-4- yl)methyl)phenyl)carbamate
36		4-chlorobenzyl (4-((3- fluoro-N- methylisonicotinamido)meth- yl)phenyl)carbamate
37		pyridin-4-ylmethyl (4-((6- methylnicotinamido)meth- yl)phenyl)carbamate
38		4-chlorobenzyl (4-((1- (methylsulfonyl)piperidin-4- yl)methyl)phenyl)carbamate
39		oxazol-5-ylmethyl (S)- (4-(1-(4- fluorobenzamido)eth- yl)phenyl)carbamate
40		4-chlorobenzyl (4-((1- acetylpiperidin-4- yl)methyl)phenyl)carbamate
41		4-chlorobenzyl (4-((N- methyl-1H-pyrazole-4- carboxamido)meth- yl)phenyl)carbamate
42		4-chlorobenzyl (4-((4- methoxy-N- methylpiperidine-1- carboxamido)meth- yl)phenyl)carbamate
43		4-chlorobenzyl (4-((1- (oxetan-3-yl)piperidin-4- yl)methyl)phenyl)carbamate
44		4-chlorobenzyl (S)-(4-(1-(3- fluoroisonicotinamido)eth- yl)phenyl)carbamate
45		4-chlorobenzyl (4-((1,4- dimethyl-1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
46		4-chlorobenzyl (S)-(4-(1- (3,4-dimethylisoxazole-5- carboxamido)eth- yl)phenyl)carbamate
47		4-methoxybenzyl (4- ((R)-1-((S)-2- (hydroxymethyl)pyrrolidin- 1-yl)-1-oxopropan-2- yl)phenyl)carbamate
48		oxazol-5-ylmethyl (4-((1- (oxetane-3- carbonyl)piperidin-4- yl)methyl)phenyl)carbamate
49		4-chlorobenzyl (4-((N- methyl-1H-pyrazole-3- carboxamido)meth- yl)phenyl)carbamate
50		4-chlorobenzyl (4-((N,1- dimethyl-1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
51		oxazol-5-ylmethyl (4-((6- methylpyridin-3- yl)methyl)phenyl)carbamate
52		pyridin-4-ylmethyl (4- ((1-(2,2- difluoroethyl)piperidin-4- yl)methyl)phenyl)carbamate
53		4-methoxybenzyl (4-((6- methylnicotinamido)meth- yl)phenyl)carbamate
54		4-chlorobenzyl (S)-(4-(1- methyl-5-oxopiperazin-2- yl)phenyl)carbamate
55		4-chlorobenzyl (4-((3,5- difluoro-N- methylisonicotinamido)meth- yl)phenyl)carbamate
56		4-chlorobenzyl (S)-(4-(1- (1-(2-methoxyethyl)-1H- pyrazole-5- carboxamido)eth- yl)phenyl)carbamate
57		4-chlorobenzyl (S)-(4-(1- (3,5- difluoroisonicotinamido)eth- yl)phenyl)carbamate
58		4-chlorobenzyl (4-((1- (dimethylcarbamoyl)piperidin-4- yl)methyl)phenyl)carbamate
59		oxazol-5-ylmethyl (4-((1- (2,2- difluoroethyl)piperidin-4- yl)methyl)phenyl)carbamate
60		4-chlorobenzyl (S)-(4-(1-(6- methylnicotinamido)eth- yl)phenyl)carbamate
61		4-methoxybenzyl (4- ((phenylmethyl)sul- fonamido)phenyl)carbamate
62		4-chlorobenzyl (4-((1- carbamoylpiperidin-4- yl)methyl)phenyl)carbamate
63		4-chlorobenzyl (4-((3- oxo-2- azabicyclo[3.1.0]hexan-2- yl)methyl)phenyl)carbamate
64		4-chlorobenzyl (4-(2- (((1r,4r)-4- methoxycyclohexyl)amino)-2- oxoethyl)phenyl)carbamate
65		(1H-pyrazol-4-yl)methyl (4-((6-methylpyridin-3- yl)methyl)phenyl)carbamate
66		thiazol-5-ylmethyl (4-((6- methylnicotinamido)meth- yl)phenyl)carbamate
67		4-methoxybenzyl (4-((1- (oxetan-3-yl)piperidin-4- yl)methyl)phenyl)carbamate
68		oxazol-5-ylmethyl (4- ((S)-1-((1R,3s,5S)-6,6- difluorobicyclo[3.1.0]hexane-3- carboxamido)eth- yl)phenyl)carbamate
69		4-chlorobenzyl (4-((5- fluoro-N-methyl-1H- pyrazole-4- carboxamido)meth- yl)phenyl)carbamate
70		oxazol-5-ylmethyl (4-((1- (2,2,2- trifluoroethyl)piperidin-4- yl)methyl)phenyl)carbamate
71		4-chlorobenzyl (4-((4- fluoro-N-methyl-1H- pyrazole-3- carboxamido)meth- yl)phenyl)carbamate
72		4-chlorobenzyl (S)-(4-(1- (4-methoxypiperidine-1- carboxamido)eth- yl)phenyl)carbamate
73		4-chlorobenzyl (4-((4- (pyrimidin-2- yl)piperazin-1- yl)methyl)phenyl)carbamate
74		4-chlorobenzyl (4-((1- cyclobutyl-N-methyl-1H- pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
75		oxazol-5-ylmethyl (S)- (4-(1-(3,3- difluorocyclobutane-1- carboxamido)eth- yl)phenyl)carbamate
76		4-chlorobenzyl (S)-(4-(1-(6- ethylnicotinamido)eth- yl)phenyl)carbamate
77		4-chlorobenzyl (4-((1-(2- methoxyethyl)-N-methyl- 1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
78		4-chlorobenzyl (4-((3- fluoroisonicotinamido)meth- yl)phenyl)carbamate
79		tert-butyl 4-(4-(((oxazol-5- ylmethoxy)carbonyl)ami- no)benzyl)piperidine-1- carboxylate
80		oxazol-5-ylmethyl (4-((1- (oxetan-3-yl)piperidin-4- yl)methyl)phenyl)carbamate
81		4-chloro-2-fluorobenzyl (S)-(4-(1-methyl-5- oxopiperazin-2- yl)phenyl)carbamate
82		4-chlorobenzyl (4-((6- ethylnicotinamido)meth- yl)phenyl)carbamate
83		4-methoxybenzyl (4-((4- (pyridin-2-yl)piperazin-1- yl)methyl)phenyl)carbamate
84		4-chlorobenzyl (4-((4- oxo-5- azaspiro[2.4]heptan-5- yl)methyl)phenyl)carbamate
85		4-chlorobenzyl (4-((N,2- dimethyloxazole-5- carboxamido)meth- yl)phenyl)carbamate
86		4-chlorobenzyl (4-((3- oxomorpholino)meth- yl)phenyl)carbamate
87		4-chlorobenzyl (4-((1- isobutyrylpiperidin-4- yl)methyl)phenyl)carbamate
88		oxazol-5-ylmethyl (4-(1- (2,2,2- trifluoroethyl)piperidin- 4-yl)phenyl)carbamate
89		4-chlorobenzyl (S)-(4-(1- (N-methylazetidine-1- carboxamido)eth- yl)phenyl)carbamate
90		4-chlorobenzyl (4-((3- methoxy-N,1-dimethyl- 1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
91		4-chlorobenzyl (4-((N- methyl-1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
92		4-chlorobenzyl (S)-(4-(1- (4-methoxy-1-methyl- 1H-pyrazole-5- carboxamido)eth- yl)phenyl)carbamate
93		4-chlorobenzyl (4-(((1- acetylpiperidin-4- yl)oxy)methyl)phenyl)carbamate
94		4-chlorobenzyl (4-((1- isobutyl-N-methyl-1H- pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
95		4-chlorobenzyl (S)-(4-(1- (3-methoxy-1-methyl- 1H-pyrazole-5- carboxamido)eth- yl)phenyl)carbamate
96		4-chlorobenzyl (S)-(4-(1- (azetidine-1- carboxamido)eth- yl)phenyl)carbamate
97		oxazol-5-ylmethyl (4- ((1S)-1-(3,3- difluorocyclopentane-1- carboxamido)eth- yl)phenyl)carbamate
98		methyl 4-(4-((((4- chlorobenzyl)oxy)car- bonyl)amino)benzyl)piperidine- 1-carboxylate
99		(1H-pyrazol-4-yl)methyl (4-(pyridin-4- ylmethyl)phenyl)carbamate
100		4-chlorobenzyl (S)-(4-(1-(6- methoxynicotinamido)eth- yl)phenyl)carbamate
101		4-chlorobenzyl (S)-(4-(1- (1-ethyl-1H-pyrazole-5- carboxamido)eth- yl)phenyl)carbamate
102		4-chlorobenzyl (4-((1- (cyclobutane- carbonyl)piperidin-4- yl)methyl)phenyl)carbamate
103		4-chlorobenzyl (S)-(4-(1- (pyrrolidine-1- carboxamido)eth- yl)phenyl)carbamate
104		4-chlorobenzyl (4-((N,6- dimethylnicotinamido)meth- yl)phenyl)carbamate
105		4-chlorobenzyl (S)-(4-(1- (isonicotinamido)eth- yl)phenyl)carbamate
106		4-(hydroxymethyl)benzyl (4-(pyridin-4- ylmethyl)phenyl)carbamate
107		4-chlorobenzyl (4-((4- (methylsulfonyl)piperazin-1- yl)methyl)phenyl)carbamate
108		4-chlorobenzyl (4-((N,3- dimethylisoxazole-4- carboxamido)meth- yl)phenyl)carbamate
109		4-chlorobenzyl (4-((2- methylpyrimidine-5- carboxamido)meth- yl)phenyl)carbamate
110		4-chlorobenzyl (S)-(4-(1- (5-methoxy-6- methylnicotinamido)eth- yl)phenyl)carbamate
111		4-chlorobenzyl (4-(2- oxo-2-(piperidin-1- yl)ethyl)phenyl)carbamate
112		4-chlorobenzyl (4-((N- methylazetidine-1- carboxamido)meth- yl)phenyl)carbamate
113		oxazol-5-ylmethyl (4-(1-(2,2- difluoroethyl)piperidin-4- yl)phenyl)carbamate
114		thiazol-5-ylmethyl (4- ((6-methylpyridin-3- yl)methyl)phenyl)carbamate
115		pyridin-4-ylmethyl (4- ((1-acetylpiperidin-4- yl)methyl)phenyl)carbamate
116		4-chlorobenzyl (4-(2-(4- hydroxy-4- methylpiperidin-1-yl)-2- oxoethyl)phenyl)carbamate
117		4-chlorobenzyl (S)-(4-(1- (tetrahydro-2H-pyran-4- carboxamido)eth- yl)phenyl)carbamate
118		4-chlorobenzyl (S)-(4-(1- (nicotinamido)eth- yl)phenyl)carbamate
119		4-chlorobenzyl (4-(2-(4- hydroxypiperidin-1-yl)-2- oxoethyl)phenyl)carbamate
120		methyl 4-(4-(((oxazol-5- ylmethoxy)carbonyl)ami- no)phenethyl)piperidine- 1-carboxylate
121		tert-butyl 4-(4-(((oxazol-5- ylmethoxy)carbonyl)ami- no)phenethyl)piperidine- 1-carboxylate
122		4-chlorobenzyl (S)-(4-(1- (oxetane-3- carboxamido)eth- yl)phenyl)carbamate
123		4-chlorobenzyl (4-((3,3- dimethyl-2- oxopyrrolidin-1- yl)methyl)phenyl)carbamate
124		4-chlorobenzyl (4-((1- methyl-2-oxopiperidine-4- carboxamido)meth- yl)phenyl)carbamate
125		4-chlorobenzyl (S)-(4-(1- (2,4-dimethyloxazole-5- carboxamido)eth- yl)phenyl)carbamate
126		4-chlorobenzyl (4- (isonicotinamidometh- yl)phenyl)carbamate
127		4-chlorobenzyl (4- ((N,1,3,4-tetramethyl- 1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
128		4-chlorobenzyl (4-((N- methylpyrrolidine-1- carboxamido)meth- yl)phenyl)carbamate
129		4-chlorobenzyl (S)-(4-(1- (1-isobutyl-1H-pyrazole-5- carboxamido)eth- yl)phenyl)carbamate
130		4-chlorobenzyl (4-((N- methyloxazole-5- carboxamido)meth- yl)phenyl)carbamate
131		4-chlorobenzyl (4-((1- isopropyl-N-methyl-1H- pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
132		oxazol-5-ylmethyl (4-(2- (1-(oxetan-3- yl)piperidin-4- yl)ethyl)phenyl)carbamate
133		4-(difluoromethyl)benzyl (4-((6- methylnicotinamido)meth- yl)phenyl)carbamate
134		4-chlorobenzyl (S)-(4-(1- (4-methoxy-N- methylpiperidine-1- carboxamido)eth- yl)phenyl)carbamate
135		4-chlorobenzyl (4-((4- methoxy-1-methyl-1H- pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
136		4-chlorobenzyl (4-((5- methylpyrazine-2- carboxamido)meth- yl)phenyl)carbamate
137		4-chlorobenzyl (S)-(4-(1- (3-ethyl-1-methyl-1H- pyrazole-5- carboxamido)eth- yl)phenyl)carbamate
138		4-chlorobenzyl (4-((3- methoxy-1-methyl-1H- pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
139		4-chlorobenzyl (S)-(4-(1- (1,3-dimethyl-1H- pyrazole-5- carboxamido)eth- yl)phenyl)carbamate
140		4-chlorobenzyl (4-((3,4- dimethylisoxazole-5- carboxamido)meth- yl)phenyl)carbamate
141		4-chlorobenzyl (S)-(4-(1- (4-fluoro-1,3-dimethyl- 1H-pyrazole-5- carboxamido)eth- yl)phenyl)carbamate
142		4-chlorobenzyl (S)-(4-(1- (4-methylisoxazole-5- carboxamido)eth- yl)phenyl)carbamate
143		4-chlorobenzyl (S)-(4-(1- (N-methylpyrrolidine-1- carboxamido)eth- yl)phenyl)carbamate
144		4-chlorobenzyl (S)-(4-(1- (3-methylazetidine-1- carboxamido)eth- yl)phenyl)carbamate
145		4-chlorobenzyl (S)-(4-(1- (4-methylpiperidine-1- carboxamido)eth- yl)phenyl)carbamate
146		4-chlorobenzyl (4-((5- fluoro-6- methylnicotinamido)meth- yl)phenyl)carbamate
147		4-chlorobenzyl (4-((3,5- difluoroisonicotin- amido)meth- yl)phenyl)carbamate
148		methyl 4-(4-(((oxazol-5- ylmethoxy)carbonyl)ami- no)phenyl)piperidine-1- carboxylate
149		4-chlorobenzyl (S)-(4-(1- (1-methyl-1H-pyrazole-5- carboxamido)eth- yl)phenyl)carbamate
150		4-chlorobenzyl (S)-(4-(1- (3-methylisoxazole-4- carboxamido)eth- yl)phenyl)carbamate
151		4-chlorobenzyl (4-(1,1- dioxidotetrahydro-2H- thiopyran-4- yl)phenyl)carbamate
152		4-chlorobenzyl (S)-(4-(1- (4-methyloxazole-5- carboxamido)eth- yl)phenyl)carbamate
153		oxazol-5-ylmethyl (4- (pyridin-4- ylmethyl)phenyl)carbamate
154		4-chlorobenzyl (S)-(4-(1- (morpholine-4- carboxamido)eth- yl)phenyl)carbamate
155		4-chlorobenzyl (4-((N,4- dimethyloxazole-2- carboxamido)meth- yl)phenyl)carbamate
156		methyl 4-(2-(4-((((4- chlorobenzyl)oxy)car- bonyl)amino)phenyl)ace- tyl)piperazine-1-carboxylate
157		4-chlorobenzyl (4-((2- methyloxazole-5- carboxamido)meth- yl)phenyl)carbamate
158		4-chlorobenzyl (4-((6- methoxynicotinamido)meth- yl)phenyl)carbamate
159		4-chlorobenzyl (S)-(4-(1-(5- fluoronicotinamido)eth- yl)phenyl)carbamate
160		4-chlorobenzyl (4-((N,3- dimethylisoxazole-5- carboxamido)meth- yl)phenyl)carbamate
161		4-chlorobenzyl (S)-(4-(2- (3-methoxypiperidin-1- yl)-2- oxoethyl)phenyl)carbamate
162		4-chlorobenzyl (4-((2- methoxypyrimidine-5- carboxamido)meth- yl)phenyl)carbamate
163		4-chlorobenzyl (S)-(4-(1-(6- isopropylnicotinamido)eth- yl)phenyl)carbamate
164		4-chlorobenzyl (S)-(4-(1-(6- (difluoromethyl)nicotinami- do)ethyl)phenyl)carbamate
165		4-chlorobenzyl (4-((4,6- dimethylnicotinamido)meth- yl)phenyl)carbamate
166		4-chlorobenzyl (4-((1-(2- methoxyethyl)-1H- pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
167		4-chlorobenzyl (4-((1- ethyl-1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
168		4-methoxybenzyl (4-((4- methyl-2-oxopiperazin-1- yl)methyl)phenyl)carbamate
169		pyridin-4-ylmethyl (4- (pyridin-4- ylmethyl)phenyl)carbamate
170		4-chlorobenzyl (S)-(4-(1- (3-methoxyazetidine-1- carboxamido)eth- yl)phenyl)carbamate
171		4-chlorobenzyl (S)-(4-(2- (3-hydroxypiperidin-1- yl)-2- oxoethyl)phenyl)carbamate
172		4-chlorobenzyl (4- (pyridin-3- ylmethyl)phenyl)carbamate
173		4-chlorobenzyl (4-((2- methylisonicotinamido)meth- yl)phenyl)carbamate
174		4-methoxybenzyl (4-((3- oxomorpholino)meth- yl)phenyl)carbamate
175		4-chlorobenzyl (4- ((pyrimidine-5- carboxamido)meth- yl)phenyl)carbamate
176		4-chlorobenzyl (4-((4- ethyl-N-methyloxazole-5- carboxamido)meth- yl)phenyl)carbamate
177		4-chlorobenzyl (4-((4-(2- hydroxy-2- methylpropyl)piperazin-1- yl)methyl)phenyl)carbamate
178		4-chlorobenzyl (4-(2-(5- methyl-2,5- diazabicyclo[4.1.0]heptan- 2-yl)-2- oxoethyl)phenyl)carbamate
179		4-chlorobenzyl (4-((3- methyloxetane-3- carboxamido)meth- yl)phenyl)carbamate
180		4-chlorobenzyl (4-((2- oxo-3- azabicyclo[3.1.0]hexan-3- yl)methyl)phenyl)carbamate
181		4-chlorobenzyl (S)-(4-(1- (1-isopropyl-1H- pyrazole-5- carboxamido)eth- yl)phenyl)carbamate
182		4-chlorobenzyl (4- ((N,2,4-trimethyloxazole-5- carboxamido)meth- yl)phenyl)carbamate
183		4-chlorobenzyl (4-(2- (2,2-dimethylazetidin-1- yl)-2- oxoethyl)phenyl)carbamate
184		4-chlorobenzyl (4-((4- methoxypiperidine-1- carboxamido)meth- yl)phenyl)carbamate
185		4-chlorobenzyl (4-((6- (difluoromethyl)nicotin- amido)methyl)phenyl)carbamate
186		pyridin-4-ylmethyl (4- ((6-methylpyridin-3- yl)methyl)phenyl)carbamate
187		4-chlorobenzyl (4- ((oxazole-5- carboxamido)meth- yl)phenyl)carbamate
188		4-chlorobenzyl (4-((4- fluoro-N,1,3-trimethyl- 1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
189		4-chlorobenzyl (S)-(4-(1- (3-methyloxetane-3- carboxamido)eth- yl)phenyl)carbamate
190		4-chlorobenzyl (4- ((N,3,4- trimethylisoxazole-5- carboxamido)meth- yl)phenyl)carbamate
191		4-chlorobenzyl (4-((4- acetylpiperazin-1- yl)methyl)phenyl)carbamate
192		4-chlorobenzyl (4-((2- methylnicotinamido)meth- yl)phenyl)carbamate
193		4-chlorobenzyl (4-((1- methyl-1H-pyrazole-4- carboxamido)meth- yl)phenyl)carbamate
194		4-chlorobenzyl (4-(2-(4- (oxetan-3-yl)piperazin-1- yl)-2- oxoethyl)phenyl)carbamate
195		4-chlorobenzyl (4-((5- methoxy-6- methylnicotinamido)meth- yl)phenyl)carbamate
196		4-(difluoromethyl)benzyl (4-(pyridin-4- ylmethyl)phenyl)carbamate
197		4-chlorobenzyl (4-((N,3- dimethyl-1H-pyrazole-4- carboxamido)meth- yl)phenyl)carbamate
198		4-chlorobenzyl (4-(1- (oxetan-3-yl)piperidin-4- yl)phenyl)carbamate
199		4-chlorobenzyl (4-(2-((6- methylpyridin-3- yl)amino)-2- oxoethyl)phenyl)carbamate
200		4-chlorobenzyl (S)-(4-(1- (3-methylisoxazole-5- carboxamido)eth- yl)phenyl)carbamate
201		thiazol-5-ylmethyl (4- (pyridin-4- ylmethyl)phenyl)carbamate
202		4-chlorobenzyl (S)-(4-(2-(2- (hydroxymethyl)pyrrolidin- 1-yl)-2- oxoethyl)phenyl)carbamate
203		4-chlorobenzyl (4-((4- fluoro-1,3-dimethyl-1H- pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
204		4-(difluoromethyl)benzyl (S)-(4-(1-methyl-5- oxopiperazin-2- yl)phenyl)carbamate
205		4-chlorobenzyl (4-((1- methyl-1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
206		4-chlorobenzyl (4- ((N,3,5-trimethyl-1H- pyrazole-4- carboxamido)meth- yl)phenyl)carbamate
207		4-chlorobenzyl (4-((3- fluoropicolinamido)meth- yl)phenyl)carbamate
208		4-chlorobenzyl (4-((3- ethyl-1-methyl-1H- pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
209		4-chlorobenzyl (4-((4- methyloxazole-5- carboxamido)meth- yl)phenyl)carbamate
210		4-chlorobenzyl (S)-(4-(1- (1-cyclobutyl-1H- pyrazole-5- carboxamido)eth- yl)phenyl)carbamate
211		4-chlorobenzyl (4-((2,4- dimethyloxazole-5- carboxamido)meth- yl)phenyl)carbamate
212		4-chlorobenzyl (4-(2-(4- fluoropiperidin-1-yl)-2- oxoethyl)phenyl)carbamate
213		4-chlorobenzyl (S)-(4-(1- (2-methoxy-6- methylnicotinamido)eth- yl)phenyl)carbamate
214		4-chlorobenzyl (4-((5- methylpicolinamido)meth- yl)phenyl)carbamate
215		4-chlorobenzyl (4-(2-(2- methylpyrrolidin-1-yl)-2- oxoethyl)phenyl)carbamate
216		4-chlorobenzyl (4- (pyridin-4- ylmethyl)phenyl)carbamate
217		4-methoxybenzyl (4-(((1- acetylpiperidin-4- yl)oxy)meth- yl)phenyl)carbamate
218		4-chlorobenzyl (S)-(4-(1- (2-methyloxazole-5- carboxamido)eth- yl)phenyl)carbamate
219		isothiazol-5-ylmethyl (4- (pyridin-4- ylmethyl)phenyl)carbamate
220		4-chlorobenzyl (4-(2- morpholino-2- oxoethyl)phenyl)carbamate
221		4-chlorobenzyl (4-(2- (((1r,4r)-4- (difluoromethoxy)cyclo- hexyl)amino)-2- oxoethyl)phenyl)carbamate
222		4-chlorobenzyl (4-((3- (methylsulfonyl)azetidin-1- yl)methyl)phenyl)carbamate
223		4-chlorobenzyl (4-((4- (oxetan-3-yl)piperazin-1- yl)methyl)phenyl)carbamate
224		4-chlorobenzyl (S)-(4-(1- (2-(oxazol-2- yl)acetamido)eth- yl)phenyl)carbamate
225		4-chlorobenzyl (4-((1,3- dimethyl-1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
226		4-chlorobenzyl (4- ((pyrazine-2- carboxamido)meth- yl)phenyl)carbamate
227		4-fluorobenzyl (4-((6- methylnicotinamido)meth- yl)phenyl)carbamate
228		4-chlorobenzyl (S)-(4- (((1-methyl-2- oxopyrrolidin-3- yl)amino)meth- yl)phenyl)carbamate
229		4-chlorobenzyl (R)-(4-(2- (3-methoxypiperidin-1-yl)-2- oxoethyl)phenyl)carbamate
230		oxazol-5-ylmethyl (4- ((S)-1-((1R,3r,5S)-6,6- difluorobicyclo[3.1.0]hexane-3- carboxamido)eth- yl)phenyl)carbamate
231		4-chlorobenzyl (4- (piperidin-4- ylmethyl)phenyl)carbamate
232		4-chlorobenzyl (4-(((1- (oxetan-3-yl)piperidin-4- yl)oxy)meth- yl)phenyl)carbamate
233		4-chlorobenzyl (4- (pyridin-2- ylmethyl)phenyl)carbamate
234		4-chlorobenzyl (4-((6- isopropylnicotinamido)meth- yl)phenyl)carbamate
235		4-chlorobenzyl (4-(2- oxo-2-(3-oxopiperazin-1- yl)ethyl)phenyl)carbamate
236		4-chlorobenzyl (S)-(4-(1- cyclobutyl-5- oxopiperazin-2- yl)phenyl)carbamate
237		4-chlorobenzyl (R)-(4-(2- (3-hydroxypiperidin-1- yl)-2- oxoethyl)phenyl)carbamate
238		4-chlorobenzyl (4-((1- (tetrahydro-2H-pyran-4- yl)-1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
239		4-chlorobenzyl (4-((6- (trifluoromethyl)nicotin- amido)methyl)phenyl)carbamate
240		4-chlorobenzyl (4-(2-(4- methylpiperidin-1-yl)-2- oxoethyl)phenyl)carbamate
241		4-chlorobenzyl (S)-(4-(1- (5-methyloxazole-4- carboxamido)eth- yl)phenyl)carbamate
242		4-chlorobenzyl (4-((2- oxooxazolidin-3- yl)methyl)phenyl)carbamate
243		4-chlorobenzyl (S)-(4-(1- (4-methyloxazole-2- carboxamido)eth- yl)phenyl)carbamate
244		4-chlorobenzyl (S)-(4-(2- (3-methylpyrrolidin-1-yl)-2- oxoethyl)phenyl)carbamate
245		4-chlorobenzyl (4-((2- methoxy-6- methylnicotinamido)meth- yl)phenyl)carbamate
246		4-chlorobenzyl (S)-(4-(1- (oxazole-5- carboxamido)eth- yl)phenyl)carbamate
247		4-chlorobenzyl (4-(1- hydroxy-1-(pyridin-4- yl)ethyl)phenyl)carbamate
248		4-chlorobenzyl (4- ((pyridazine-3- carboxamido)meth- yl)phenyl)carbamate
249		4-chlorobenzyl (R)-(4- ((2-oxo-5-(pyridin-3- yl)pyrrolidin-1- yl)methyl)phenyl)carbamate
250		4-chlorobenzyl (4-((5- fluoro-N- methylnicotinamido)meth- yl)phenyl)carbamate
251		4-chlorobenzyl (4-((3- methylisoxazole-4- carboxamido)meth- yl)phenyl)carbamate
252		oxazol-5-ylmethyl (4-(2- (piperidin-4- yl)ethyl)phenyl)carbamate
253		4-chlorobenzyl (4-((4- methoxy-N,1-dimethyl- 1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
254		4-chlorobenzyl (4-((1- methyl-1H-pyrrole-3- carboxamido)meth- yl)phenyl)carbamate
255		4-chlorobenzyl (4-((1- methyl-1H-pyrazole-3- carboxamido)meth- yl)phenyl)carbamate
256		4-chlorobenzyl (R)-(4-(2- (3-methylpiperidin-1-yl)-2- oxoethyl)phenyl)carbamate
257		4-chlorobenzyl (S)-(4-(2-(2- (hydroxymethyl)piperidin- 1-yl)-2- oxoethyl)phenyl)carbamate
258		4-chlorobenzyl (4-((4-(2,2- difluoroethyl)piperazine-1- carboxamido)meth- yl)phenyl)carbamate
259		4-chlorobenzyl (S)-(4-(1- (3-(difluoromethyl)-1- methyl-1H-pyrazole-5- carboxamido)eth- yl)phenyl)carbamate
260		4-chlorobenzyl (S)-(4-(1- (4-ethyloxazole-5- carboxamido)eth- yl)phenyl)carbamate
261		4-chlorobenzyl (S)-(4-(2- (3-methylpiperidin-1-yl)-2- oxoethyl)phenyl)carbamate
262		4-methoxybenzyl (4- (pyridin-4- ylmethyl)phenyl)carbamate
263		4-methoxybenzyl (S)-(4- (1-methyl-5- oxopiperazin-2- yl)phenyl)carbamate
264		4-chlorobenzyl (4-(2- (methyl(6-methylpyridin- 3-yl)amino)-2- oxoethyl)phenyl)carbamate
265		4-chlorobenzyl (4- ((azetidine-1- carboxamido)meth- yl)phenyl)carbamate
266		oxazol-5-ylmethyl (S)- (4-(1- (cyclopropanecarbox- amido)ethyl)phenyl)carbamate
267		4-chlorobenzyl (S)-(4-(1- (5-methyloxazole-2- carboxamido)eth- yl)phenyl)carbamate
268		4-chlorobenzyl (4-((4- methylisoxazole-5- carboxamido)meth- yl)phenyl)carbamate
269		oxazol-5-ylmethyl (4-(2- (4-(oxetan-3- yl)piperazin-1- yl)ethyl)phenyl)carbamate
270		4-chlorobenzyl (4- ((morpholine-4- carboxamido)meth- yl)phenyl)carbamate
271		4-chlorobenzyl (4-((5- fluoronicotinamido)meth- yl)phenyl)carbamate
272		4-chlorobenzyl (4- (picolinamidometh- yl)phenyl)carbamate
273		4-chlorobenzyl (4-(2-((5- fluoropyridin-3- yl)amino)-2- oxoethyl)phenyl)carbamate
274		4-chlorobenzyl (4-(2- (4,4-difluoropiperidin-1- yl)-2- oxoethyl)phenyl)carbamate
275		4- (difluoromethoxy)benzyl (4-((6- methylnicotinamido)meth- yl)phenyl)carbamate
276		4-chlorobenzyl (4-((4- methyloxazole-2- carboxamido)meth- yl)phenyl)carbamate
277		4-chlorobenzyl (4-((1- methyl-5-oxopyrrolidine-3- carboxamido)meth- yl)phenyl)carbamate
278		4-fluorobenzyl (S)-(4-(1- methyl-5-oxopiperazin-2- yl)phenyl)carbamate
279		4-chlorobenzyl (4- (pyrimidin-2- ylmethyl)phenyl)carbamate
280		4-chlorobenzyl (4-(2- (((1s,4s)-4- methoxycyclohexyl)amino)-2- oxoethyl)phenyl)carbamate
281		4-chlorobenzyl (4-(4- acetylmorpholin-2- yl)phenyl)carbamate
282		4-chlorobenzyl (4-(2-(4- (2,2- difluoroethyl)piperazin- 1-yl)-2- oxoethyl)phenyl)carbamate
283		4-chlorobenzyl (4-(2-(4- methoxypiperidin-1-yl)-2- oxoethyl)phenyl)carbamate
284		4-chlorobenzyl (4-((4- methyl-3-oxopiperazin-1- yl)methyl)phenyl)carbamate
285		4-chlorobenzyl (4- ((tetrahydro-2H-pyran-4- carboxamido)meth- yl)phenyl)carbamate
286		4-chlorobenzyl (4- ((piperidine-1- carboxamido)meth- yl)phenyl)carbamate
287		4-chlorobenzyl (R)-(4-(2-(2- (hydroxymethyl)piperidin- 1-yl)-2- oxoethyl)phenyl)carbamate
288		tert-butyl 3-((4-((((4- chlorobenzyl)oxy)car- bonyl)amino)benzyl)oxy)aze- tidine-1-carboxylate
289		4-chlorobenzyl (4-((3- ethyl-N,1-dimethyl-1H- pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
290		4-chlorobenzyl (S)-(4-(1- (4-cyclopropyloxazole-5- carboxamido)eth- yl)phenyl)carbamate
291		4-methoxybenzyl (4-(((1- (oxetan-3-yl)piperidin-4- yl)oxy)methyl)phenyl)carbamate
292		4-chlorobenzyl (4-((6- methylpyridin-3- yl)methyl)phenyl)carbamate
293		oxazol-5-ylmethyl (4-((1-(2- methoxyethyl)piperidin-4- yl)methyl)phenyl)carbamate
294		4-chlorobenzyl (4-((5- methyloxazole-2- carboxamido)meth- yl)phenyl)carbamate
295		4-chlorobenzyl (4-((2-(1- methyl-1H-pyrazol-3- yl)acetamido)meth- yl)phenyl)carbamate
296		oxazol-5-ylmethyl (4-(1- hydroxy-1-(pyridin-4- yl)ethyl)phenyl)carbamate
297		4-chlorobenzyl (4-((2- (oxazol-2- yl)acetamido)meth- yl)phenyl)carbamate
298		4-chlorobenzyl (4-((6- (difluoromethyl)-N- methylnicotinamido)meth- yl)phenyl)carbamate
299		isothiazol-4-ylmethyl (4- (pyridin-4- ylmethyl)phenyl)carbamate
300		4-chlorobenzyl (4-(2- oxo-2-((pyrazin-2- ylmethyl)amino)eth- yl)phenyl)carbamate
301		4-chlorobenzyl (4-((1- isopropyl-1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
302		4-chlorobenzyl (4-((1- isobutyl-1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
303		4-chlorobenzyl (4- (pyrazin-2- ylmethyl)phenyl)carbamate
304		4-chlorobenzyl (S)-(4-(1- isopropyl-5- oxopiperazin-2- yl)phenyl)carbamate
305		4-chlorobenzyl (4-((5- fluoropicolinamido)meth- yl)phenyl)carbamate
306		4-cyanobenzyl (4- (pyridin-4- ylmethyl)phenyl)carbamate
307		4-chlorobenzyl (4- benzylphenyl)carbamate
308		4-chlorobenzyl (4-(2- oxo-2-((tetrahydro-2H- pyran-4- yl)amino)ethyl)phenyl)carbamate
309		4-chlorobenzyl (4-((4,4- difluoropiperidine-1- carboxamido)meth- yl)phenyl)carbamate
310		4-chlorobenzyl (4- ((oxetane-3- carboxamido)meth- yl)phenyl)carbamate
311		4-chlorobenzyl (4-((2- (oxazol-5- yl)acetamido)meth- yl)phenyl)carbamate
312		4-chlorobenzyl (4-(1,1- difluoro-2-oxo-2-(3- oxopiperazin-1- yl)ethyl)phenyl)carbamate
313		oxazol-5-ylmethyl (4-(1- (oxetan-3-yl)piperidin-4- yl)phenyl)carbamate
314		4-chlorobenzyl (4-((1- methyl-1H-pyrazol-5- yl)methyl)phenyl)carbamate
315		4-chlorobenzyl (4-((2-(1- methyl-1H-pyrazol-4- yl)acetamido)meth- yl)phenyl)carbamate
316		pyridin-4-ylmethyl (4- ((1-(oxetan-3- yl)piperidin-4- yl)methyl)phenyl)carbamate
317		4-chlorobenzyl (R)-(4-(2- (3-hydroxypyrrolidin-1- yl)-2- oxoethyl)phenyl)carbamate
318		4-methoxybenzyl (4-((4- (oxetan-3-yl)piperazin-1- yl)methyl)phenyl)carbamate
319		4-chlorobenzyl (S)-(4-(2- (3-hydroxypyrrolidin-1-yl)-2- oxoethyl)phenyl)carbamate
320		oxazol-5-ylmethyl (4- (piperidin-4- ylmethyl)phenyl)carbamate
321		4-chlorobenzyl (4-((5- methyloxazole-4- carboxamido)meth- yl)phenyl)carbamate
322		4-chlorobenzyl (4-((5- methyl-1,3,4-oxadiazol-2- yl)methyl)phenyl)carbamate
323		4-chlorobenzyl (4-(2- (((6-methylpyridin-3- yl)methyl)amino)-2- oxoethyl)phenyl)carbamate
324		4-methoxybenzyl (4-((3- (methylsulfonyl)azetidin-1- yl)methyl)phenyl)carbamate
325		4-methoxybenzyl (4-((4- methyl-3-oxopiperazin-1- yl)methyl)phenyl)carbamate
326		pyridazin-4-ylmethyl (4- (pyridin-4- ylmethyl)phenyl)carbamate
327		4-chlorobenzyl (4-((1- cyclobutyl-1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
328		4-(difluoromethyl)benzyl (4-((6-methylpyridin-3- yl)methyl)phenyl)carbamate
329		thiazol-5-ylmethyl (4-(1- hydroxy-1-(pyridin-4- yl)ethyl)phenyl)carbamate
330		4-chlorobenzyl (4-((2- (isoxazol-4- yl)acetamido)meth- yl)phenyl)carbamate
331		4-fluorobenzyl (4-((6- methylpyridin-3- yl)methyl)phenyl)carbamate
332		4-chlorobenzyl (4-(2-(4- methyl-3-oxopiperazin-1- yl)-2- oxoethyl)phenyl)carbamate
333		isoxazol-4-ylmethyl (4- (pyridin-4- ylmethyl)phenyl)carbamate
334		4-chlorobenzyl (4-((2- (1H-pyrazol-1- yl)acetamido)meth- yl)phenyl)carbamate
335		4-chlorobenzyl (4-(N- benzyl-N-methyl- sulfamoyl)phenyl)carbamate
336		4-chlorobenzyl (4- (thiazol-2- ylmethyl)phenyl)carbamate
337		4-chlorobenzyl (R)-(4- (N-methyl-N- (tetrahydrofuran-3- yl)sulfamoyl)phenyl)carbamate
338		4-chlorobenzyl (4-(2- oxo-2-(((1r,4r)-4- (trifluoromethoxy)cyclo- hexyl)amino)eth- yl)phenyl)carbamate
339		4-chlorobenzyl (4-(2- (oxetan-3-ylamino)-2- oxoethyl)phenyl)carbamate
340		4-chlorobenzyl (4-((N,5- dimethyloxazole-4- carboxamido)meth- yl)phenyl)carbamate
341		4-methoxybenzyl (4-((S)- 1-((S)-2- (hydroxymethyl)pyrrolidin- 1-yl)-1-oxopropan-2- yl)phenyl)carbamate
342		4-chlorobenzyl (4-(N- methyl-N- (tetrahydrofuran-3- yl)sulfamoyl)phenyl)carbamate
343		4-chlorobenzyl (4-((4- cyclopropyloxazole-5- carboxamido)meth- yl)phenyl)carbamate
344		4-chlorobenzyl (4-((3- methyl-1,2,4-oxadiazol-5- yl)methyl)phenyl)carbamate
345		4-chlorobenzyl (4-((3- (difluoromethyl)-1- methyl-1H-pyrazole-5- carboxamido)meth- yl)phenyl)carbamate
346		4-chlorobenzyl (S)-(4-(1- (oxetan-3-yl)-5- oxopiperazin-2- yl)phenyl)carbamate
347		4-chlorobenzyl (4-((4- ethyloxazole-5- carboxamido)meth- yl)phenyl)carbamate
348		oxazol-5-ylmethyl (4-(1-(2- methoxyethyl)piperidin- 4-yl)phenyl)carbamate
349		pyrimidin-4-ylmethyl (4- (pyridin-4- ylmethyl)phenyl)carbamate
350		4-chlorobenzyl (4- (isothiazol-5- ylmethyl)phenyl)carbamate
351		4-chlorobenzyl (4- (thiazol-5- ylmethyl)phenyl)carbamate
352		4-chlorobenzyl (4-(N- methyl-N-(oxetan-3- yl)sulfamoyl)phenyl)carbamate
353		4-chlorobenzyl (4- (oxazol-4- ylmethyl)phenyl)carbamate
354		4-chlorobenzyl (4-(((1- (oxetan-3-yl)azetidin-3- yl)oxy)methyl)phenyl)carbamate
355		(1-methyl-1H-pyrazol-4- yl)methyl (4-(pyridin-4- ylmethyl)phenyl)carbamate
356		4-chlorobenzyl (4-(((6- methylpyridine)-3- sulfonamido)meth- yl)phenyl)carbamate
357		oxazol-5-ylmethyl (4-(2- isobutyryl-2- azaspiro[3.3]heptan-6- yl)phenyl)carbamate
358		oxazol-5-ylmethyl (4-(2- acetyl-2- azaspiro[3.3]heptan-6- yl)phenyl)carbamate
359
	Diastereoisomer 1
360
	Diastereoisomer 2
361
	Diastereoisomer 1
362
	Diastereoisomer 2
363
	Diastereoisomer 1
364
	Diastereoisomer 2
365		oxazol-5-ylmethyl (R)- (4-(1- (methylsulfonyl)piperidin- 3-yl)phenyl)carbamate
366		oxazol-5-ylmethyl (R)- (4-(1-(N,N- dimethylsulfamoyl)piperidin-3- yl)phenyl)carbamate
367		oxazol-5-ylmethyl (3- fluoro-4-((6-propionyl-6- azaspiro[3.4]octan-2- yl)methyl)phenyl)carbamate
368		oxazol-5-ylmethyl (3- fluoro-4-((6-isobutyryl-6- azaspiro[3.4]octan-2- yl)methyl)phenyl)carbamate
369		oxazol-5-ylmethyl (3- fluoro-4-((6- (ethylsulfonyl)-6- azaspiro[3.4]octan-2- yl)methyl)phenyl)carbamate
370		oxazol-5-ylmethyl (3- fluoro-4-((6- (methylsulfonyl)-6- azaspiro[3.4]octan-2- yl)methyl)phenyl)carbamate
371		methyl 2-(2-fluoro-4- (((oxazol-5- ylmethoxy)carbonyl)ami- no)benzyl)-6- azaspiro[3.4]octane-6- carboxylate
372
	Diastereoisomer 1
373
	Diastereoisomer 2
374		oxazol-5-ylmethyl (4-((6- acetyl-6- azaspiro[3.4]octan-2- yl)methyl)-3- fluorophenyl)carbamate
375		oxazol-5-ylmethyl (R)- (4-(1-acetylpiperidin-3- yl)phenyl)carbamate
376		oxazol-5-ylmethyl (R)- (4-(1- (dimethylcarbamoyl)piperidin-3- yl)phenyl)carbamate
377		tert-butyl 2-(2-fluoro-4- (((oxazol-5- ylmethoxy)carbonyl)ami- no)benzyl)-6- azaspiro[3.4]octane-6- carboxylate
378		oxazol-5-ylmethyl (4-((6- azaspiro[3.4]octan-2- yl)methyl)-3- fluorophenyl)carbamate
379		oxazol-5-ylmethyl (4-((6- (dimethylcarbamoyl)-6- azaspiro[3.4]octan-2- yl)methyl)-3- fluorophenyl)carbamate
380		oxazol-5-ylmethyl (S)- (4-(1-(oxetan-3- yl)piperidin-3- yl)phenyl)carbamate
381		oxazol-5-ylmethyl (S)- (4-(1-acetylpiperidin-3- yl)phenyl)carbamate
382		oxazol-5-ylmethyl (S)- (4-(1- (methylsulfonyl)piperidin- 3-yl)phenyl)carbamate
383		methyl (S)-3-(4- (((oxazol-5- ylmethoxy)carbonyl)ami- no)phenyl)piperidine-1- carboxylate
384		oxazol-5-ylmethyl (S)- (4-(1-(N,N-dimethyl- sulfamoyl)piperidin-3- yl)phenyl)carbamate
385		oxazol-5-ylmethyl (S)- (4-(1-(dimethyl- carbamoyl)piperidin-3- yl)phenyl)carbamate
386		oxazol-5-ylmethyl (4-((2- (ethylsulfonyl)-2- azaspiro[3.3]heptan-6- yl)methyl)-3- fluorophenyl)carbamate
387		oxazol-5-ylmethyl (4-(2- (N,N- dimethylsulfamoyl)-2- azaspiro[3.3]heptan-6- yl)-3- fluorophenyl)carbamate
388		oxazol-5-ylmethyl (3- fluoro-4-(2- (methylsulfonyl)-2- azaspiro[3.3]heptan-6- yl)phenyl)carbamate
389		oxazol-5-ylmethyl (4-((8- (morpholine-4-carbonyl)- 8-azabicyclo[3.2.1]octan-3- yl)methyl)phenyl)carbamate
390		oxazol-5-ylmethyl (4-((8- (piperidine-1-carbonyl)- 8-azabicyclo[3.2.1]octan-3- yl)methyl)phenyl)carbamate
391		oxazol-5-ylmethyl (4-((8- (pyrrolidine-1-carbonyl)- 8-azabicyclo[3.2.1]octan-3- yl)methyl)phenyl)carbamate
392		oxazol-5-ylmethyl (4-((8- (azetidine-1-carbonyl)-8- azabicyclo[3.2.1]octan-3- yl)methyl)phenyl)carbamate
393		oxazol-5-ylmethyl (4-((8- (azetidin-1-ylsulfonyl)-8- azabicyclo[3.2.1]octan-3- yl)methyl)phenyl)carbamate
394		oxazol-5-ylmethyl (4-((8- (cyclobutylsulfonyl)-8- azabicyclo[3.2.1]octan-3- yl)methyl)phenyl)carbamate
395		oxazol-5-ylmethyl (4-((8- (cyclopropylsulfonyl)-8- azabicyclo[3.2.1]octan-3- yl)methyl)phenyl)carbamate
396		methyl 6-(2-fluoro-4- (((oxazol-5- ylmethoxy)carbonyl)ami- no)benzyl)-2- azaspiro[3.3]heptane-2- carboxylate
397		oxazol-5-ylmethyl (3- fluoro-4-((2-(oxetan-3- yl)-2- azaspiro[3.3]heptan-6- yl)methyl)phenyl)carbamate
398		oxazol-5-ylmethyl (4-((2- (dimethylcarbamoyl)-2- azaspiro[3.3]heptan-6- yl)methyl)-3- fluorophenyl)carbamate
399		oxazol-5-ylmethyl (4-((2- (N,N- dimethylsulfamoyl)-2- azaspiro[3.3]heptan-6- yl)methyl)-3- fluorophenyl)carbamate
400		oxazol-5-ylmethyl (4-(2- (dimethylcarbamoyl)-2- azaspiro[3.3]heptan-6- yl)-3- fluorophenyl)carbamate
401		oxazol-5-ylmethyl (4-(2- acetyl-2- azaspiro[3.3]heptan-6- yl)-3- fluorophenyl)carbamate
402		oxazol-5-ylmethyl (3- fluoro-4-((2-propionyl-2- azaspiro[3.3]heptan-6- yl)methyl)phenyl)carbamate
403		oxazol-5-ylmethyl (3- fluoro-4-((2-isobutyryl-2- azaspiro[3.3]heptan-6- yl)methyl)phenyl)carbamate
404		oxazol-5-ylmethyl (3- fluoro-4-((2- (methylsulfonyl)-2- azaspiro[3.3]heptan-6- yl)methyl)phenyl)carbamate
405		oxazol-5-ylmethyl (4-((8- (N,N- dimethylsulfamoyl)-8- azabicyclo[3.2.1]octan-3- yl)methyl)phenyl)carbamate
406		oxazol-5-ylmethyl (4-((8- (methylsulfonyl)-8- azabicyclo[3.2.1]octan-3- yl)methyl)phenyl)carbamate
407		methyl 3-(4-(((oxazol-5- ylmethoxy)carbonyl)ami- no)benzyl)-8- azabicyclo[3.2.1]octane- 8-carboxylate
408		oxazol-5-ylmethyl (4-((8- (dimethylcarbamoyl)-8- azabicyclo[3.2.1]octan-3- yl)methyl)phenyl)carbamate
409		oxazol-5-ylmethyl (4-((8- isobutyryl-8- azabicyclo[3.2.1]octan-3- yl)methyl)phenyl)carbamate
410		oxazol-5-ylmethyl (4-((8- acetyl-8- azabicyclo[3.2.1]octan-3- yl)methyl)phenyl)carbamate
411		oxazol-5-ylmethyl (4-(1- (dimethylcarbamoyl)piperidin- 4-yl)-3- fluorophenyl)carbamate
412		oxazol-5-ylmethyl (3- fluoro-4-(1- propionylpiperidin-4- yl)phenyl)carbamate
413		oxazol-5-ylmethyl (4-(1- acetylpiperidin-4-yl)-3- fluorophenyl)carbamate
414		oxazol-5-ylmethyl (3- fluoro-4-(1- isobutyrylpiperidin-4- yl)phenyl)carbamate
415		oxazol-5-ylmethyl (3- fluoro-4-(1- (methylsulfonyl)piperidin- 4-yl)phenyl)carbamate
416		oxazol-5-ylmethyl (4-(1- (N,N-dimethyl- sulfamoyl)piperidin- 4-yl)-3- fluorophenyl)carbamate
417		methyl 4-(2-fluoro-4- (((oxazol-5- ylmethoxy)carbonyl)ami- no)phenyl)piperidine-1- carboxylate
418		oxazol-5-ylmethyl (4-((4- (ethylsulfonyl)-4- azaspiro[2.5]octan-7- yl)methyl)phenyl)carbamate
419		oxazol-5-ylmethyl (4-((4- (methylsulfonyl)-4- azaspiro[2.5]octan-7- yl)methyl)phenyl)carbamate
420		oxazol-5-ylmethyl (4-((3- (methylsulfonyl)-3- azabicyclo[3.2.1]octan-8- yl)methyl)phenyl)carbamate
421		methyl 8-(4-(((oxazol-5- ylmethoxy)carbonyl)ami- no)benzyl)-3- azabicyclo[3.2.1]octane- 3-carboxylate
422		oxazol-5-ylmethyl (4-((3- (dimethylcarbamoyl)-3- azabicyclo[3.2.1]octan-8- yl)methyl)phenyl)carbamate
423		oxazol-5-ylmethyl (4-((3- isobutyryl-3- azabicyclo[3.2.1]octan-8- yl)methyl)phenyl)carbamate
424		oxazol-5-ylmethyl (4-((3- acetyl-3- azabicyclo[3.2.1]octan-8- yl)methyl)phenyl)carbamate
425		oxazol-5-ylmethyl (4-((3- (oxetan-3-yl)-3- azabicyclo[3.2.1]octan-8- yl)methyl)phenyl)carbamate
426		oxazol-5-ylmethyl (4-((3- azabicyclo[3.2.1]octan-8- yl)methyl)phenyl)carbamate
427		oxazol-5-ylmethyl (4-(1- (ethylsulfonyl)piperidin- 4-yl)phenyl)carbamate
428		oxazol-5-ylmethyl (4-(1- (azetidin-1- ylsulfonyl)piperidin-4- yl)phenyl)carbamate
429		oxazol-5-ylmethyl (4-(1- (azetidine-1- carbonyl)piperidin-4- yl)phenyl)carbamate
430		oxazol-5-ylmethyl (4-(1- propionylpiperidin-4- yl)phenyl)carbamate
431		oxazol-5-ylmethyl (4-(1- (cyclopropane- carbonyl)piperidin-4- yl)phenyl)carbamate
432		oxazol-5-ylmethyl (4-(1- (N,N-dimethyl- sulfamoyl)piperidin-4- yl)phenyl)carbamate
433		oxazol-5-ylmethyl (4-((3- (N,N- dimethylsulfamoyl)-3- azabicyclo[3.1.1]heptan-6- yl)methyl)phenyl)carbamate
434		oxazol-5-ylmethyl (4-((3- (methylsulfonyl)-3- azabicyclo[3.1.1]heptan-6- yl)methyl)phenyl)carbamate
435		methyl 6-(4-(((oxazol-5- ylmethoxy)carbonyl)ami- no)benzyl)-3- azabicyclo[3.1.1]heptane- 3-carboxylate
436		oxazol-5-ylmethyl (4-((3- (dimethylcarbamoyl)-3- azabicyclo[3.1.1]heptan-6- yl)methyl)phenyl)carbamate
437		oxazol-5-ylmethyl (4-((3- isobutyryl-3- azabicyclo[3.1.1]heptan-6- yl)methyl)phenyl)carbamate
438		oxazol-5-ylmethyl (4-((3- acetyl-3- azabicyclo[3.1.1]heptan-6- yl)methyl)phenyl)carbamate
439		oxazol-5-ylmethyl (4-((3- (oxetan-3-yl)-3- azabicyclo[3.1.1]heptan-6- yl)methyl)phenyl)carbamate
440		oxazol-5-ylmethyl (4-((4- (N,N- dimethylsulfamoyl)-4- azaspiro[2.5]octan-7- yl)methyl)phenyl)carbamate
441		oxazol-5-ylmethyl (4-((4- (oxetan-3-yl)-4- azaspiro[2.5]octan-7- yl)methyl)phenyl)carbamate
442		oxazol-5-ylmethyl (4-((4- (dimethylcarbamoyl)-4- azaspiro[2.5]octan-7- yl)methyl)phenyl)carbamate
443		methyl 7-(4-(((oxazol-5- ylmethoxy)carbonyl)ami- no)benzyl)-4- azaspiro[2.5]octane-4- carboxylate
444		oxazol-5-ylmethyl (4-((4- acetyl-4- azaspiro[2.5]octan-7- yl)methyl)phenyl)carbamate
445		oxazol-5-ylmethyl (4-(3- acetyl-3- azabicyclo[3.2.1]octan-8- yl)phenyl)carbamate
446		isopropyl 4-(4-(((oxazol-5- ylmethoxy)carbonyl)ami- no)benzyl)piperidine-1- carboxylate
447		oxazol-5-ylmethyl (4-((1- (N,N-dimethyl- sulfamoyl)piperidin- 4-yl)methyl)-3- fluorophenyl)carbamate
448		oxazol-5-ylmethyl (3- fluoro-4-((1- (methylsulfonyl)piperidin-4- yl)methyl)phenyl)carbamate
449		oxazol-5-ylmethyl (4-((1- (dimethylcarbamoyl)piperidin- 4-yl)methyl)-3- fluorophenyl)carbamate
450		methyl 4-(2-fluoro-4- (((oxazol-5- ylmethoxy)carbonyl)ami- no)benzyl)piperidine-1- carboxylate
451		oxazol-5-ylmethyl (4-((1- acetylpiperidin-4- yl)methyl)-3- fluorophenyl)carbamate
452		oxazol-5-ylmethyl (3- fluoro-4-((1-(oxetan-3- yl)piperidin-4- yl)methyl)phenyl)carbamate
453		oxazol-5-ylmethyl (4-((2- (methylsulfonyl)-2- azabicyclo[4.1.0]heptan-5- yl)methyl)phenyl)carbamate
454		oxazol-5-ylmethyl (4-((2- (dimethylcarbamoyl)-2- azabicyclo[4.1.0]heptan-5- yl)methyl)phenyl)carbamate
455		oxazol-5-ylmethyl (4-((2- (oxetan-3-yl)-2- azabicyclo[4.1.0]heptan-5- yl)methyl)phenyl)carbamate
456		methyl 5-(4-(((oxazol-5- ylmethoxy)carbonyl)ami- no)benzyl)-2- azabicyclo[4.1.0]heptane- 2-carboxylate
457		oxazol-5-ylmethyl (4-((2- acetyl-2- azabicyclo[4.1.0]heptan-5- yl)methyl)phenyl)carbamate
458		oxazol-5-ylmethyl (4-((1- (morpholine-4- carbonyl)piperidin-4- yl)methyl)phenyl)carbamate
459		oxazol-5-ylmethyl (4-((1- (cyclobutylsulfonyl)piperidin-4- yl)methyl)phenyl)carbamate
460		oxazol-5-ylmethyl (4-((1- (cyclopropylsul- fonyl)piperidin-4- yl)methyl)phenyl)carbamate
461		oxazol-5-ylmethyl (4-((1- (piperidine-1- carbonyl)piperidin-4- yl)methyl)phenyl)carbamate
462		oxazol-5-ylmethyl (4-((1- (pyrrolidine-1- carbonyl)piperidin-4- yl)methyl)phenyl)carbamate
463		oxazol-5-ylmethyl (4-((1- (3,3-difluoroazetidine-1- carbonyl)piperidin-4- yl)methyl)phenyl)carbamate
464		oxazol-5-ylmethyl (4-((1- (isopropylsulfonyl)piperidin-4- yl)methyl)phenyl)carbamate
465		oxazol-5-ylmethyl (4-((1- (azetidin-1- ylsulfonyl)piperidin-4- yl)methyl)phenyl)carbamate
466		thiazol-5-ylmethyl (4- ((1-(oxetan-3- yl)piperidin-4- yl)methyl)phenyl)carbamate
467		thiazol-5-ylmethyl (4- ((1-(2,2,2- trifluoroethyl)piperidin-4- yl)methyl)phenyl)carbamate
468		oxazol-5-ylmethyl (4-((1- (azetidine-1- carbonyl)piperidin-4- yl)methyl)phenyl)carbamate
469		oxazol-5-ylmethyl (4-((1- (cyclobutane- carbonyl)piperidin-4- yl)methyl)phenyl)carbamate
470		oxazol-5-ylmethyl (4-((1- (3,3-difluorocyclobutane- 1-carbonyl)piperidin-4- yl)methyl)phenyl)carbamate
471		oxazol-5-ylmethyl (4-((1- (oxetan-2- ylmethyl)piperidin-4- yl)methyl)phenyl)carbamate
472		oxazol-5-ylmethyl (4-((2- acetyl-2- azaspiro[3.3]heptan-6- yl)methyl)-3- fluorophenyl)carbamate

In some embodiments, provided herein is a compound of Formula (I), or any variation thereof, or a pharmaceutically acceptable salt of any of the foregoing, selected from the group consisting of:

• 4-methoxybenzyl (4-((2-(pyridin-3-yl)pyrrolidin-1-yl)methyl)phenyl)carbamate;
• 4-carbamoylbenzyl (4-((2-(pyridin-3-yl)pyrrolidin-1-yl)methyl)phenyl)carbamate; pyridin-4-ylmethyl (4-((2-(pyridin-3-yl)pyrrolidin-1-yl)methyl)phenyl)carbamate;
• 4-(hydroxymethyl)benzyl (4-((2-(pyridin-3-yl)pyrrolidin-1-yl)methyl)phenyl)carbamate; oxazol-5-ylmethyl (4-((2-(pyridin-3-yl)pyrrolidin-1-yl)methyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(1,3,4-trimethyl-1H-pyrazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-5-carboxamido)ethyl)phenyl)carbamate;
• oxazol-5-ylmethyl (4-(1-(6,6-difluorospiro[3.3]heptane-2-carboxamido)ethyl)phenyl)carbamate;
• oxazol-5-ylmethyl (4-(1-(4-fluorobenzamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(3-fluoroisonicotinamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(3,4-dimethylisoxazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-methoxybenzyl (4-(1-(2-(hydroxymethyl)pyrrolidin-1-yl)-1-oxopropan-2-yl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-methyl-5-oxopiperazin-2-yl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(1-(2-methoxyethyl)-1H-pyrazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(3,5-difluoroisonicotinamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(6-methylnicotinamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(2-((4-methoxycyclohexyl)amino)-2-oxoethyl)phenyl)carbamate;
• oxazol-5-ylmethyl (4-(1-(6,6-difluorobicyclo[3.1.0]hexane-3-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(4-methoxypiperidine-1-carboxamido)ethyl)phenyl)carbamate;
• oxazol-5-ylmethyl (4-(1-(3,3-difluorocyclobutane-1-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(6-ethylnicotinamido)ethyl)phenyl)carbamate;
• 4-chloro-2-fluorobenzyl (4-(1-methyl-5-oxopiperazin-2-yl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(N-methylazetidine-1-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(4-methoxy-1-methyl-1H-pyrazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(3-methoxy-1-methyl-1H-pyrazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(azetidine-1-carboxamido)ethyl)phenyl)carbamate;
• oxazol-5-ylmethyl (4-(1-(3,3-difluorocyclopentane-1-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(6-methoxynicotinamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(1-ethyl-1H-pyrazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(pyrrolidine-1-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(isonicotinamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(5-methoxy-6-methylnicotinamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(tetrahydro-2H-pyran-4-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(nicotinamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(oxetane-3-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(2,4-dimethyloxazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(1-isobutyl-1H-pyrazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(4-methoxy-N-methylpiperidine-1-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(3-ethyl-1-methyl-1H-pyrazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(1,3-dimethyl-1H-pyrazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(4-fluoro-1,3-dimethyl-1H-pyrazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(4-methylisoxazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(N-methylpyrrolidine-1-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(3-methylazetidine-1-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(4-methylpiperidine-1-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(1-methyl-1H-pyrazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(3-methylisoxazole-4-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(4-methyloxazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(morpholine-4-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(5-fluoronicotinamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(2-(3-methoxypiperidin-1-yl)-2-oxoethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(6-isopropylnicotinamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(6-(difluoromethyl)nicotinamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(3-methoxyazetidine-1-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(2-(3-hydroxypiperidin-1-yl)-2-oxoethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(1-isopropyl-1H-pyrazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(3-methyloxetane-3-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(3-methylisoxazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(2-(2-(hydroxymethyl)pyrrolidin-1-yl)-2-oxoethyl)phenyl)carbamate;
• 4-(difluoromethyl)benzyl (4-(1-methyl-5-oxopiperazin-2-yl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(1-cyclobutyl-1H-pyrazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(2-methoxy-6-methylnicotinamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(2-methyloxazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(2-((-4-(difluoromethoxy)cyclohexyl)amino)-2-oxoethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(2-(oxazol-2-yl)acetamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(((1-methyl-2-oxopyrrolidin-3-yl)amino)methyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(2-(3-methoxypiperidin-1-yl)-2-oxoethyl)phenyl)carbamate;
• oxazol-5-ylmethyl (4-(1-(6,6-difluorobicyclo[3.1.0]hexane-3-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-cyclobutyl-5-oxopiperazin-2-yl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(5-methyloxazole-4-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(4-methyloxazole-2-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(2-(3-methylpyrrolidin-1-yl)-2-oxoethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(oxazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-((2-oxo-5-(pyridin-3-yl)pyrrolidin-1-yl)methyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(2-(3-methylpiperidin-1-yl)-2-oxoethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(2-(2-(hydroxymethyl)piperidin-1-yl)-2-oxoethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(3-(difluoromethyl)-1-methyl-1H-pyrazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(4-ethyloxazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(2-(3-methylpiperidin-1-yl)-2-oxoethyl)phenyl)carbamate;
• 4-methoxybenzyl (4-(1-methyl-5-oxopiperazin-2-yl)phenyl)carbamate;
• oxazol-5-ylmethyl (4-(1-(cyclopropanecarboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(5-methyloxazole-2-carboxamido)ethyl)phenyl)carbamate;
• 4-fluorobenzyl (4-(1-methyl-5-oxopiperazin-2-yl)phenyl)carbamate;
• 4-chlorobenzyl (4-(2-((-4-methoxycyclohexyl)amino)-2-oxoethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(2-(2-(hydroxymethyl)piperidin-1-yl)-2-oxoethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-(4-cyclopropyloxazole-5-carboxamido)ethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(1-isopropyl-5-oxopiperazin-2-yl)phenyl)carbamate;
• 4-chlorobenzyl (4-(2-(3-hydroxypyrrolidin-1-yl)-2-oxoethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(2-(3-hydroxypyrrolidin-1-yl)-2-oxoethyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(N-methyl-N-(tetrahydrofuran-3-yl)sulfamoyl)phenyl)carbamate;
• 4-chlorobenzyl (4-(2-oxo-2-((4-(trifluoromethoxy)cyclohexyl)amino)ethyl)phenyl)carbamate;
• 4-methoxybenzyl (4-(1-(2-(hydroxymethyl)pyrrolidin-1-yl)-1-oxopropan-2-yl)phenyl)carbamate;
• oxazol-5-ylmethyl (3-fluoro-4-(6-(methylsulfonyl)-6-azaspiro[3.4]octan-2-yl)phenyl)carbamate;
• oxazol-5-ylmethyl (3-fluoro-4-(6-isobutyryl-6-azaspiro[3.4]octan-2-yl)phenyl)carbamate;
• oxazol-5-ylmethyl (4-(6-(dimethylcarbamoyl)-6-azaspiro[3.4]octan-2-yl)-3-fluorophenyl)carbamate;
• oxazol-5-ylmethyl (4-(1-(methylsulfonyl)piperidin-3-yl)phenyl)carbamate;
• oxazol-5-ylmethyl (4-(1-(N,N-dimethylsulfamoyl)piperidin-3-yl)phenyl)carbamate;
• oxazol-5-ylmethyl (3-fluoro-4-((6-propionyl-6-azaspiro[3.4]octan-2-yl)methyl)phenyl)carbamate;
• oxazol-5-ylmethyl (3-fluoro-4-((6-isobutyryl-6-azaspiro[3.4]octan-2-yl)methyl)phenyl)carbamate;
• oxazol-5-ylmethyl (3-fluoro-4-((6-(ethylsulfonyl)-6-azaspiro[3.4]octan-2-yl)methyl)phenyl)carbamate;
• oxazol-5-ylmethyl (3-fluoro-4-((6-(methylsulfonyl)-6-azaspiro[3.4]octan-2-yl)methyl)phenyl)carbamate;
• methyl 2-(2-fluoro-4-(((oxazol-5-ylmethoxy)carbonyl)amino)benzyl)-6-azaspiro[3.4]octane-6-carboxylate;
• oxazol-5-ylmethyl (4-(6-acetyl-6-azaspiro[3.4]octan-2-yl)-3-fluorophenyl)carbamate;
• oxazol-5-ylmethyl (4-((6-acetyl-6-azaspiro[3.4]octan-2-yl)methyl)-3-fluorophenyl)carbamate;
• oxazol-5-ylmethyl (4-(1-acetylpiperidin-3-yl)phenyl)carbamate;
• tert-butyl 2-(2-fluoro-4-(((oxazol-5-ylmethoxy)carbonyl)amino)benzyl)-6-azaspiro[3.4]octane-6-carboxylate;
• oxazol-5-ylmethyl (4-((6-azaspiro[3.4]octan-2-yl)methyl)-3-fluorophenyl)carbamate;
• oxazol-5-ylmethyl (4-((6-(dimethylcarbamoyl)-6-azaspiro[3.4]octan-2-yl)methyl)-3-fluorophenyl)carbamate;
• oxazol-5-ylmethyl (4-(1-(oxetan-3-yl)piperidin-3-yl)phenyl)carbamate;
• methyl 3-(4-(((oxazol-5-ylmethoxy)carbonyl)amino)phenyl)piperidine-1-carboxylate;
• oxazol-5-ylmethyl (4-(1-(dimethylcarbamoyl)piperidin-3-yl)phenyl)carbamate; and
• 4-chlorobenzyl (4-(1-(oxetan-3-yl)-5-oxopiperazin-2-yl)phenyl)carbamate,or a pharmaceutically acceptable salt of any of the foregoing.

In some variations, any of the compounds described herein, such as a compound of Formula (I), or any variation thereof, or a compound of Table 1 may be deuterated (e.g., one or more hydrogen atom is replaced by a deuterium atom). In some of these variations, the compound is deuterated at a single site. In other variations, the compound is deuterated at multiple sites. Deuterated compounds can be prepared from deuterated starting materials in a manner similar to the preparation of the corresponding non-deuterated compounds. Hydrogen atoms may also be replaced with deuterium atoms using other method known in the art.

Formula (I) is intended to represent compounds having structures depicted by the structural formula as well as certain variations or forms. In particular, compounds of any formula given herein may have asymmetric centers and therefore exist in different enantiomeric or diastereomeric forms. All optical isomers and stereoisomers of the compounds of the general formula, and mixtures thereof in any ratio, are considered within the scope of the formula. Thus, any formula given herein is intended to represent a racemate, one or more enantiomeric forms, one or more diastereomeric forms, one or more atropisomeric forms, and mixtures thereof in any ratio. Where a compound of Table 1 is depicted with a particular stereochemical configuration, also provided herein is any alternative stereochemical configuration of the compound, as well as a mixture of stereoisomers of the compound in any ratio. For example, where a compound of Table 1 has a stereocenter that is in an “S” stereochemical configuration, also provided herein is enantiomer of the compound wherein that stereocenter is in an “R” stereochemical configuration. Likewise, when a compound of Table 1 has a stereocenter that is in an “R” configuration, also provided herein is enantiomer of the compound in an “S” stereochemical configuration. Also provided are mixtures of the compound with both the “S” and the “R” stereochemical configuration. Additionally, if a compound of Table 1 has two or more stereocenters, also provided are any enantiomer or diastereomer of the compound. For example, if a compound of Table 1 contains a first stereocenter and a second stereocenter with “R” and “R” stereochemical configurations, respectively, also provided are stereoisomers of the compound having first and second stereocenters with “S” and “S” stereochemical configurations, respectively, “S” and “R” stereochemical configurations, respectively, and “R” and “S” stereochemical configurations, respectively. If a compound of Table 1 contains a first stereocenter and a second stereocenter with “S” and “S” stereochemical configurations, respectively, also provided are stereoisomers of the compound having first and second stereocenters with “R” and “R” stereochemical configurations, respectively, “S” and “R” stereochemical configurations, respectively, and “R” and “S” stereochemical configurations, respectively. If a compound of Table 1 contains a first stereocenter and a second stereocenter with “S” and “R” stereochemical configurations, respectively, also provided are stereoisomers of the compound having first and second stereocenters with “R” and “S” stereochemical configurations, respectively, “R” and “R” stereochemical configurations, respectively, and “S” and “S” stereochemical configurations, respectively. Similarly, if a compound of Table 1 contains a first stereocenter and a second stereocenter with “R” and “S” stereochemical configurations, respectively, also provided are stereoisomers of the compound having first and second stereocenters with “S” and “R” stereochemical configurations, respectively, “R” and “R” stereochemical configurations, respectively, and “S” and “S” stereochemical configurations, respectively. Furthermore, certain structures may exist as geometric isomers (i.e., cis and trans isomers), as tautomers, or as atropisomers. Additionally, any formula given herein is intended to refer also to any one of hydrates, solvates, and amorphous and polymorphic forms of such compounds, and mixtures thereof, even if such forms are not listed explicitly. In some embodiments, the solvent is water and the solvates are hydrates.

Representative examples of compounds detailed herein, including intermediates and final compounds, are depicted in the tables and elsewhere herein. It is understood that in one aspect, any of the compounds may be used in the methods detailed herein, including, where applicable, intermediate compounds that may be isolated and administered to an individual or subject.

The compounds depicted herein may be present as salts even if salts are not depicted, and it is understood that the compositions and methods provided herein embrace all salts and solvates of the compounds depicted here, as well as the non-salt and non-solvate form of the compound, as is well understood by the skilled artisan. In some embodiments, the salts of the compounds provided herein are pharmaceutically acceptable salts.

In one variation, the compounds herein are synthetic compounds prepared for administration to an individual or subject. In another variation, compositions are provided containing a compound in substantially pure form. In another variation, provided are pharmaceutical compositions comprising a compound detailed herein and a pharmaceutically acceptable carrier. In another variation, methods of administering a compound are provided. The purified forms, pharmaceutical compositions and methods of administering the compounds are suitable for any compound or form thereof detailed herein.

Any variation or embodiment of Ring A, Ring B, L, R^A, R^B, R^C, R^D, m, n, p, R^A1R^A2, R^L, R^C1, R^B1, and R^B2 as provided herein can be combined with every other variation or embodiment of Ring A, Ring B, L, R^A, R^B, R^C, R^D, m, n, p, R^A1, R^A2, R^L, R^C1, R^B1, and R^B2, the same as if each combination had been individually and specifically described.

Other embodiments will be apparent to those skilled in the art from the following detailed description.

As used herein, when any variable occurs more than one time in a chemical formula, its definition on each occurrence is independent of its definition at every other occurrence.

The compound names provided herein, including in Table 1, are provided by ChemBioDraw Professional. One of skilled in the art would understand that the compounds may be named or identified using various commonly recognized nomenclature systems and symbols. By way of example, the compounds may be named or identified with common names, systematic or non-systematic names. The nomenclature systems and symbols that are commonly recognized in the art of chemistry include, for example, Chemical Abstract Service (CAS), ChemBioDraw Ultra, and International Union of Pure and Applied Chemistry (IUPAC).

Compositions

Also provided are compositions, such as pharmaceutical compositions, that include a compound disclosed and/or described herein and one or more additional medicinal agents, pharmaceutical agents, adjuvants, carriers, excipients, and the like. Suitable medicinal and pharmaceutical agents include those described herein. In some embodiments, the pharmaceutical composition includes a pharmaceutically acceptable excipient or adjuvant and at least one chemical entity as described herein. Examples of pharmaceutically acceptable excipients include, but are not limited to, mannitol, lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, sodium crosscarmellose, glucose, gelatin, sucrose, and magnesium carbonate. In some embodiments, provided are compositions, such as pharmaceutical compositions that contain one or more compounds described herein, or a pharmaceutically acceptable salt thereof.

In some embodiments, provided is a pharmaceutically acceptable composition comprising a compound of Formula (I), or a compound of Table 1, or a pharmaceutically acceptable salt thereof. In some aspects, a composition may contain a synthetic intermediate that may be used in the preparation of a compound described herein. The compositions described herein may contain any other suitable active or inactive agents.

Any of the compositions described herein may be sterile or contain components that are sterile. Sterilization can be achieved by methods known in the art. Any of the compositions described herein may contain one or more compounds or conjugates that are substantially pure.

Also provided are packaged pharmaceutical compositions, comprising a pharmaceutical composition as described herein and instructions for using the composition to treat a patient suffering from a disease or condition described herein.

Methods of Use

Compounds and compositions detailed herein, such as a pharmaceutical composition comprising a compound of any formula provided herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient, may be used in methods of administration and treatment as provided herein.

Without being bound by theory, the compounds and pharmaceutical compositions disclosed herein are believed to act by modulating nicotinamide phosphoribosyltransferase (NAMPT). In some embodiments, the compounds and pharmaceutical compositions disclosed herein are activators of NAMPT. In some embodiments, provided are methods of treating a disease or condition mediated by NAMPT activity in an individual or subject, comprising administering to the individual or subject in need thereof a compound of Formula (I), or a compound of Table 1, or a pharmaceutically acceptable salt thereof. In some embodiments, provided are methods of treating cancer, a hyperproliferative disease or condition, an inflammatory disease or condition, a metabolic disorder, a cardiac disease or condition, chemotherapy induced tissue damage, a renal disease, a metabolic disease, a neurological disease or injury, a neurodegenerative disorder or disease, diseases caused by impaired stem cell function, diseases caused by DNA damage, primary mitochondrial disorders, or a muscle disease or muscle wasting disorder in an individual or subject, comprising administering to the individual or subject in need thereof a compound of Formula (I), or a compound of Table 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I), or a compound of Table 1, or a pharmaceutically acceptable salt thereof, are capable of CNS penetration and have the ability to boost NAD levels in the brain for potential treatment of CNS diseases.

In some embodiments, the compounds and pharmaceutical compositions disclosed herein may have the ability to s prevent a disease or disorder (i.e., causing the clinical symptoms of the disease or disorder not to develop). In some embodiments, this encompasses situations where the disease or disorder is not currently being experienced but is expected to arise. In some embodiments, when used in a prophylactic manner, the compounds and pharmaceutical compositions disclosed and/or described herein may prevent a disease or disorder from developing or lessen the extent of a disease or disorder that may develop.

In some embodiments, provided are methods of treating a disease or condition, comprising administering to the individual or subject in need thereof a compound of Formula (I), or a compound of Table 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the disease or condition is selected from the group consisting of:

• • Hereditary motor and sensory neuropathies including Charcot-Marie Tooth Disease and hereditary sensory neuropathy type I, and the subset of fatty acid oxidation disorders that induce peripheral neuropathy;
  • Mitochondrial encephalomyopathies (including but not limited to Leber Hereditary Optic Neuropathy, MELAS, Leigh Syndrome, Chronic Progressive External Opthalmoplegia, Kearn's Sayre Syndrome, Alper's Disease, Autosomal Dominant Optic Atrophy, Friedreich's Ataxia, and Congenital Lactic Acidosis);
  • Concussion;
  • Ataxia Telangectasia;
  • Dysfunction of a variety of tissues including the central and peripheral nervous system, muscle, and immune system following viral infection including but not limited to SARS-CoV-2;
  • Treatment of obesity by raising NAD+ in the hypothalamus and peripheral tissues;
  • Treatment of hypertension by raising NAD+ systemically, including in the medulla oblongata and peripheral vasculature;
  • Alzheimer's Disease, including Mild Cognitive Impairment; and
  • Encephalitis due to viral (including but not limited to COVID-19, Herpes simplex, Varicella zoster, enterovirus, flavivirus) or bacterial infection, autoimmune disease, or insect bites (including Lyme's Disease).

Also provided herein is the use of a compound of Formula (I), or a compound of Table 1, or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treatment of a disease or condition mediated by NAMPT activity in a subject. In some aspects, provided is a compound or composition as described herein for use in a method of treatment of the human or animal body by therapy. In some embodiments, provided herein are compounds of Formula (I), or a compound of Table 1, or a pharmaceutically acceptable salt thereof, for use in a method of treatment of the human or animal body by therapy. In some embodiments, provided herein are compounds of Formula (I), or a compound of Table 1, or a pharmaceutically acceptable salt thereof, for use in treating a disease or condition mediated by NAMPT activity. In some embodiments, the disease or condition is selected from the group consisting of cancer, a hyperproliferative disease or condition, an inflammatory disease or condition, a metabolic disorder, a cardiac disease or condition, chemotherapy induced tissue damage, a renal disease, a metabolic disease, a neurological disease or injury, a neurodegenerative disorder or disease, diseases caused by impaired stem cell function, diseases caused by DNA damage, primary mitochondrial disorders, or a muscle disease or muscle wasting disorder.

Also provided herein are compositions (including pharmaceutical compositions) as described herein for the use in treating, preventing, and/or delaying the onset and/or development of a disease described herein and other methods described herein. In certain embodiments, the composition comprises a pharmaceutical formulation which is present in a unit dosage form.

In some embodiments, the subject is a mammal. In some embodiments, the subject is a mouse, rat, dog, cat, rabbit, pig, sheep, horse, cow, or human. In some embodiments, the subject is a human.

There are numerous conditions in which small molecule-mediated stimulation of NAMPT activity that boosts NAD+ levels would potentially be clinically beneficial (Strømland et al., Biochem Soc Trans. 2019, 47(1):119-130; Ralto et al., Nat Rev Nephrol. 2019; Fang et al., Trends Mol Med. 2017, 23(10):899-916; Yoshino et al., Cell Metab. 2011,14(4):528-36; Yang and Sauve, Biochim Biophys Acta. 2016, 1864:1787-1800; Verdin, Science. 2015, 350(6265):1208-13). These conditions include, but are not limited to, cardiac diseases, chemotherapy induced tissue damage, renal diseases, metabolic diseases, muscular diseases, neurological diseases and injuries, diseases caused by impaired stem cell function, and DNA damage and primary mitochondrial disorders. In some embodiments, the disease or condition mediated by NAMPT activity is a cardiac disease, chemotherapy induced tissue damage, a renal disease, a metabolic disease, a muscular disease, a neurological disease or injury, a disease caused by impaired stem cell function, or DNA damage and primary mitochondrial disorder.

Cardiac diseases. In various preclinical models of heart failure NAD as well as NAMPT levels are decreased. In these models, cardiac function can be rescued, either by restoring NAD via oral supplementation or overexpression of NAMPT (Diguet et al, Circulation. 2018, 137:2256-2273; Zheng et al., Clin Sci (Lond). 2019, 133(13):1505-1521; Smyrnias et al., J Am Coll Cardiol. 2019, 73(14):1795-1806). Thus, increasing the catalytic efficiency of NAMPT with a small molecule activator to compensate for the decreased protein levels is a promising strategy to treat various forms of heart failure.

Chemotherapy induced tissue damage. Use of chemotherapy regimens frequently is limited by toxicity to healthy tissues and severe oxidative stress is thought to play a major role. NAD boosting has been shown to trigger a strong antioxidant response. Therefore, NAMPT activators are considered broadly useful in various settings of chemotherapy to prevent reversible and irreversible secondary pathologies. Examples are anthracycline and trastuzumab cardiotoxicity, cisplatin induced kidney injury, peripheral neuropathies induced by cisplatin, paclitaxel, vincristine and other agents. Neuroprotection by NAMPT activation is also useful in treating/preventing chemotherapy associated cognitive (“chemo brain”), which is caused by destruction of healthy nerve tissue, both during active treatment and long after treatment has been halted. For instance, see Zheng et al., Clin Sci (Lond). 2019, 133(13):1505-1521.

Renal diseases. Renal diseases are highly prevalent and an area of urgent unmet medical need. In approximately 3% of hospitalized patients, acute kidney injury (AKI) is diagnosed. A subset of patients will progress to chronic kidney disease that may require long-term dialysis or kidney transplantation. A key feature of kidney dysfunction is a decrease in the activities of SIRT1 and SIRT3, characterized by a reduction of the sirtuin substrate NAD, primarily due to impairment of de novo NAD+ synthesis. NAMPT is robustly expressed during kidney injury, thus small molecule activation with NAMPT is considered an effective measure to prevent AKI. Similarly, kidney mesangial cell hypertrophy exhibits depletion of NAD+, and restoration of intracellular NAD+ levels is considered efficacious. For instance, see Poyan Mehr et al., Nat Med. 2018, September; 24(9): 1351-9.

Metabolic disease. NAD+ boosting improves insulin sensitivity, dyslipidemia, mitochondrial function in metabolic disease and protects from/improves non-alcoholic and alcoholic steatohepatitis in preclinical models. More than 3 million people per year in the U.S. alone are diagnosed with non-alcoholic steatohepatitis and it is one of the leading causes of liver transplantation. See Guarino and Dufour, Metabolites. 2019 Sep. 10; 9(9), pii: E180; Yoshino et al., Cell Metab. 2011, 14(4):528-36.

Muscular diseases. Preclinical data has suggested that NAD+ boosting strategies could alleviate skeletal muscle dysfunction in a number of conditions, including Duchenne's muscular dystrophy, and age-related sarcopenia. See Zhang et al., Clin Sci (Lond). 2019, 133(13):1505-1521; Mohamed et al., Aging (Albany NY). 2014, 6(10):820-34; Ryu et al., Sci Transl Med. 2016, 8(361):361ra139.

Neurological diseases and injuries. Repletion of NAD by means of NAMPT activation is neuroprotective and of therapeutic benefit in a wide range of preclinical models of neurological diseases and injuries, including age-related cognitive decline, glaucoma, ischemic stroke, and ALS. See Johnson et al., NPJ Aging Mech Dis. 2018, 4:10; Harlan et al., J Biol Chem. 2016, 291(20):10836-46; Zhao et al., Stroke. 2015, July; 46(7):1966-74; Williams et al., Front Neurosci. 2017 Apr. 25; 11:232; Blacher et al Nature, 2019, volume 572, 474-480; Harlan et al., 2020. Experimental Neurology 327:113219.

Diseases caused by impaired stem cell function. NAD boosting promotes stem cell activation and hematopoiesis and is useful in accelerating the expansion of stem cell populations following a stem cell transplant. See Pi et al., Aging (Albany NY). 2019, 11(11):3505-3522.

DNA damage disorders and primary mitochondrial disorders. NAMPT activators will also be useful in the treatment of DNA damage disorders which are associated with an accelerated aging phenotype, such as Xeroderma pigmentosum, Cockayne syndrome, and Ataxia telangiectasia. Similarly, there are several primary mitochondrial disorders with shared symptoms and manifestations for which NAD boosting via NAMPT activation may be a suitable therapeutic intervention. See Fang et al, Cell. 2014, 157(4):882-896; Khan et al, EMBO Mol Med. 2014, June; 6(6):721-31; Cerutti et al., Cell Metab. 2014, 19(6):1042-9.

Provided in some embodiments are methods of treating a disease or condition mediated by NAMPT activity in a subject in need thereof, comprising administering to the individual or subject in need thereof a compound of Formula (I), or a compound of Table 1, or a pharmaceutically acceptable salt thereof, wherein the disease or condition is selected from the group consisting of cardiac diseases, chemotherapy induced tissue damage, renal diseases, metabolic diseases, muscular diseases, neurological diseases and injuries, diseases caused by impaired stem cell function, and DNA damage and primary mitochondrial disorders.

Additional applications of small molecule NAMPT activators are provided in Table 2.

TABLE 2
Cancer and     Anthracycline and trastuzumab cardiotoxicity
Chemotherapy   Proteasome inhibitor cardiotoxicity
induced tissue Cisplatin induced kidney injury
damage         Prevention/treatment of cognitive dysfunction resulting
               from chemotherapy (“chemo brain”)
               Chemotherapy induced impairment of hematopoiesis
               and myelosuppression
               Cachexia of cancer
               Chemoprevention of non-melanoma skin cancer in high
               risk patients
               chemoprevention of hepatocellular carcinoma
Cardiovascular Heart failure with reduced ejection fraction
diseases       Heart failure with preserved ejection fraction
               Hypertrophic cardiomyopathy
               Cardiac arrhythmias
               Duchenne Muscular Dystrophy-related cardiac
               dysfunction
               Cardiac dysfunction associated with Scleroderma,
               Lupus, Mitochondrial Disorders, Kawasaki Disease
               Hypertension
               Myocardial Infarction
Renal diseases Acute kidney injury including nephropathy following
               major surgeries including cardiac and vascular surgeries
               Acute kidney injury following hypotension,
               hemorrhagic shock, or cardiac arrest
               Acute kidney injury following exposure to contrast
               imaging agents used for MRI, CT scans, or other
               imaging modalities, particularly in the context of
               diabetes
               Chronic kidney disease
               Glomerular nephritis
               Kidney mesangial cell hypertrophy
               Arterial venous fistula maturation
Chronic        Chronic obstructive pulmonary disease
inflammatory   Asthma
and fibrotic   Scleroderma
diseases       Dermatomyositis
               Lupus erythematosus
               Rheumatoid arthritis and spondyloarthropathy
               Juvenile idiopathic arthritis
               Crohn's disease
               Inflammatory Bowel Disease
               Eczema
               Psoriasis and psoriatic arthritis
               Idiopathic pulmonary fibrosis
Vascular       Arterial and venous thrombosis
diseases       Ischemic Stroke
               Arteriosclerosis
Metabolic      Obesity
dysfunction    Diabetes
               Metabolic Syndrome
               Alcoholic steatohepatitis
               Non-alcoholic steatohepatitis
               Dyslipidemia
               Diabetic neuropathy
               Diabetic gastroparesis
Muscular       Muscular dystrophies, including: Duchenne, Becker's,
diseases       Congenital, Distal, Emery-Dreifuss', Facioscapulo-
               humeral, Limb-girdle, myotonic, and oculopharyngeal
               Sarcopenia
               Frailty
               Polymyositis
               Muscle stem cell senescence developed in the
               context of nutritional deficiencies
               Non-mitochondrial myopathies such as inherited
               myopathies, myotonia, congenital myopathies selected
               from nemaline myopathy, multi/minicore myopathy,
               centronuclear myopathy and metabolic myopathies,
               inflammatory myopathies
Neurological   Depression
diseases       Frontotemporal dementia
and injuries   Multiple sclerosis
               Amyotrophic lateral sclerosis
               Peripheral neuropathy due to diabetes, chemotherapy
               Alzheimer's disease, including mild cognitive
               impairment
               Parkinson's disease
               Huntington's Disease
               Spinal muscular atrophy
               Spinocerebellar ataxias
               Spastic paraplegias
               Glaucoma
               Age-related macular degeneration
               Age-related cognitive decline
               Noise induced and age-related hearing loss
               Ischemic stroke
               Traumatic brain injury
               Neonatal nerve damage
               Optic nerve injury
               Spinal cord injuries
               Peripheral neuropathies or tissue inflammation induced
               by cisplatin, paclitaxel, vincristine, other
               chemotherapeutic agents, or radiation.
               Peripheral neuropathies (length and non-length
               dependent) affecting motor, sensory, or autonomic
               nerves, arising from: diabetes, impaired glucose
               tolerance, hypertension, infection, trauma, autoimmune
               disorders, vasculitis, arteriosclerosis, vitamin
               deficiencies (particularly B6 and B12), alcoholism, liver
               or kidney disease, or exposure to toxins
DNA damage     Xeroderma pigmentosum
disorders      Cockayne syndrome
and Primary    Ataxia telangiectasia
Mitochondrial  MEGDEL syndrome
Disorders      Charcot-Marie-Tooth type 2
               Primary Mitochondrial Diseases (Disorders) including
               NARP, MELAS, Chronic Progressive External
               Ophthalmoplegia, Leigh's disease, Leber's Hereditary
               Optic Neuropathy, MERRF, Barth Syndrome, Luft
               Disease, Kearns Sayre Syndrome, Autosomal dominant
               optic atrophy
               Friedreich's ataxia
               Werner syndrome
General        Tissue repair following physical trauma, hemorrhagic
               shock, tissue grafting, organ transplant including heart,
               lung, liver, and kidney
               Stem cell therapies, including hematopoietic stem cell
               transfer, allogenic mesenchymal stem therapy for acute
               graft-vs-host disease, limbal stem cell deficiency due to
               genetic or acquired conditions that compromise normal
               turnover of the corneal epithelium

In some embodiments, the disease or condition mediated by NAMPT activity is cancer and chemotherapy-induced tissue damage, a cardiovascular disease, a renal disease, chronic inflammatory and fibrotic disease, a vascular disease, metabolic dysfunction, a muscular disease, a neurological disease or injury, or a DNA damage disorder or primary mitochondrial disorder. Provided in some embodiments are methods of treating a disease or condition mediated by NAMPT activity in a subject in need thereof, comprising administering to the individual or subject in need thereof a compound of Formula (I), or a compound of Table 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the disease or condition is cancer or chemotherapy induced tissue damage, a cardiovascular disease, a renal disease, a chronic inflammatory or fibrotic disease, a vascular disease, metabolic dysfunction, a muscular disease, a neurological disease or injury, a DNA damage disorder or Primary Mitochondrial Disorder, including any of the diseases listed in Table 2.

Dosages

The compounds and compositions disclosed and/or described herein are administered at a therapeutically effective dosage, e.g., a dosage sufficient to provide treatment for the disease state. While human dosage levels have yet to be optimized for the chemical entities described herein, generally, a daily dose ranges from about 0.01 to 100 mg/kg of body weight; in some embodiments, from about 0.05 to 10.0 mg/kg of body weight, and in some embodiments, from about 0.10 to 1.4 mg/kg of body weight. Thus, for administration to a 70 kg person, in some embodiments, the dosage range would be about from 0.7 to 7000 mg per day; in some embodiments, about from 3.5 to 700.0 mg per day, and in some embodiments, about from 7 to 100.0 mg per day. The amount of the chemical entity administered will be dependent, for example, on the subject and disease state being treated, the severity of the affliction, the manner and schedule of administration and the judgment of the prescribing physician. For example, an exemplary dosage range for oral administration is from about 5 mg to about 500 mg per day, and an exemplary intravenous administration dosage is from about 5 mg to about 500 mg per day, each depending upon the compound pharmacokinetics.

A daily dose is the total amount administered in a day. A daily dose may be, but is not limited to be, administered each day, every other day, each week, every 2 weeks, every month, or at a varied interval. In some embodiments, the daily dose is administered for a period ranging from a single day to the life of the subject. In some embodiments, the daily dose is administered once a day. In some embodiments, the daily dose is administered in multiple divided doses, such as in 2, 3, or 4 divided doses. In some embodiments, the daily dose is administered in 2 divided doses.

Administration of the compounds and compositions disclosed and/or described herein can be via any accepted mode of administration for therapeutic agents including, but not limited to, oral, sublingual, subcutaneous, parenteral, intravenous, intranasal, topical, transdermal, intraperitoneal, intramuscular, intrapulmonary, vaginal, rectal, or intraocular administration. In some embodiments, the compound or composition is administered orally or intravenously. In some embodiments, the compound or composition disclosed and/or described herein is administered orally.

Pharmaceutically acceptable compositions include solid, semi-solid, liquid and aerosol dosage forms, such as tablet, capsule, powder, liquid, suspension, suppository, and aerosol forms. The compounds disclosed and/or described herein can also be administered in sustained or controlled release dosage forms (e.g., controlled/sustained release pill, depot injection, osmotic pump, or transdermal (including electrotransport) patch forms) for prolonged timed, and/or pulsed administration at a predetermined rate. In some embodiments, the compositions are provided in unit dosage forms suitable for single administration of a precise dose.

The compounds disclosed and/or described herein can be administered either alone or in combination with one or more conventional pharmaceutical carriers or excipients (e.g., mannitol, lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, sodium crosscarmellose, glucose, gelatin, sucrose, magnesium carbonate). If desired, the pharmaceutical composition can also contain minor amounts of nontoxic auxiliary substances such as wetting agents, emulsifying agents, solubilizing agents, pH buffering agents and the like (e.g., sodium acetate, sodium citrate, cyclodextrine derivatives, sorbitan monolaurate, triethanolamine acetate, triethanolamine oleate). Generally, depending on the intended mode of administration, the pharmaceutical composition will contain about 0.005% to 95%, or about 0.5% to 50%, by weight of a compound disclosed and/or described herein. Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in this art; for example, see Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pennsylvania.

In some embodiments, the compositions will take the form of a pill or tablet and thus the composition may contain, along with a compounds disclosed and/or described herein, one or more of a diluent (e.g., lactose, sucrose, dicalcium phosphate), a lubricant (e.g., magnesium stearate), and/or a binder (e.g., starch, gum acacia, polyvinylpyrrolidine, gelatin, cellulose, cellulose derivatives). Other solid dosage forms include a powder, marume, solution or suspension (e.g., in propylene carbonate, vegetable oils or triglycerides) encapsulated in a gelatin capsule.

Liquid pharmaceutically administrable compositions can, for example, be prepared by dissolving, dispersing or suspending etc. a compound disclosed and/or described herein and optional pharmaceutical additives in a carrier (e.g., water, saline, aqueous dextrose, glycerol, glycols, ethanol or the like) to form a solution or suspension. Injectables can be prepared in conventional forms, either as liquid solutions or suspensions, as emulsions, or in solid forms suitable for dissolution or suspension in liquid prior to injection. The percentage of the compound contained in such parenteral compositions depends, for example, on the physical nature of the compound, the activity of the compound and the needs of the subject. However, percentages of active ingredient of 0.01% to 10% in solution are employable, and may be higher if the composition is a solid which will be subsequently diluted to another concentration. In some embodiments, the composition will comprise from about 0.2 to 2% of a compound disclosed and/or described herein in solution.

Pharmaceutical compositions of the compounds disclosed and/or described herein may also be administered to the respiratory tract as an aerosol or solution for a nebulizer, or as a microfine powder for insufflation, alone or in combination with an inert carrier such as lactose. In such a case, the particles of the pharmaceutical composition may have diameters of less than 50 microns, or in some embodiments, less than 10 microns.

In addition, pharmaceutical compositions can include a compound disclosed and/or described herein and one or more additional medicinal agents, pharmaceutical agents, adjuvants, and the like. Suitable medicinal and pharmaceutical agents include those described herein.

Kits

Also provided are articles of manufacture and kits containing any of the compounds or pharmaceutical compositions provided herein. The article of manufacture may comprise a container with a label. Suitable containers include, for example, bottles, vials, and test tubes. The containers may be formed from a variety of materials such as glass or plastic. The container may hold a pharmaceutical composition provided herein. The label on the container may indicate that the pharmaceutical composition is used for preventing, treating or suppressing a condition described herein, and may also indicate directions for either in vivo or in vitro use.

In one aspect, provided herein are kits containing a compound or composition described herein and instructions for use. The kits may contain instructions for use in the treatment of a heart disease in an individual or subject in need thereof. A kit may additionally contain any materials or equipment that may be used in the administration of the compound or composition, such as vials, syringes, or IV bags. A kit may also contain sterile packaging.

Combinations

The compounds and compositions described and/or disclosed herein may be administered alone or in combination with other therapies and/or therapeutic agents useful in the treatment of the aforementioned disorders, diseases, or conditions.

ENUMERATED EMBODIMENTS

The following enumerated embodiments are representative of some aspects of the invention.

• • Enumerated Embodiment 1. A compound of Formula (I)

• • or a pharmaceutically acceptable salt thereof, wherein:
  • Ring A is: i) 5- to 6-membered heteroaryl optionally substituted with 1 to 4 R^A, or

• • each R^A is independently selected from the group consisting of:
  • halogen;
  • cyano;
  • C₁-C₆ alkyl optionally substituted with 1 to 3 independently selected halogens or —OH;
  • —O(C₁-C₆ alkyl) optionally substituted with 1 to 3 independently selected halogens; and
  • —C(O)NR^A1R^A2, wherein R^A1 and R^A2 are each independently hydrogen or C₁-C₆ alkyl;
  • R^D is selected from the group consisting of:
  • halogen;
  • cyano;
  • C₁-C₆ alkyl optionally substituted with 1 to 3 independently selected halogens or —OH;
  • —O(C₁-C₆ alkyl) optionally substituted with 1 to 3 independently selected halogens; and
  • —C(O)NR^A1R^A2, wherein R^A1 and R^A2 are each independently hydrogen or C₁-C₆ alkyl;
  • L is selected from the group consisting of a bond, C₁-C₆ alkylene,
  • #—O—(C₁-C₆ alkylene)-$, #—C(O)—(C₁-C₆ alkylene)-$,
  • #—(C₁-C₆ alkylene)-C(O)—$, #—N(R^L)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-N(R^L)—$,
  • #—(C₁-C₆ alkylene)-N(R^L)—(C₁-C₆ alkylene)-$,
  • #—C(O)—N(R^L)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-C(O)—N(R^L)—$,
  • #—N(R^L)—C(O)—CH₂-$, #—(C₁-C₆ alkylene)-N(R^L)—C(O)—$,
  • #—(C₁-C₆ alkylene)-C(O)—N(R^L)—(C₁-C₆ alkylene)-$,
  • #—(C₁-C₆ alkylene)-N(R^L)—C(O)—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-N(R^L)—S(O)₂-$,
  • #—N(R^L)—S(O)₂—(C₁-C₆ alkylene)-$, #—(C₁-C₆ alkylene)-S(O)₂—N(R^L)—$, #—S(O)₂—N(R^L)—(C₁-C₆ alkylene)-$, #—S(O)₂—N(R^L)—$, and #—N(C₁-C₆ alkyl)-S(O)₂-$, wherein #represents the attachment point to ring B, and $ represents the attachment point to the remainder of the molecule;
  • wherein each C₁-C₆ alkylene of L is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C₁-C₆ alkyl; and
  • wherein each R^L is independently hydrogen or C₁-C₆ alkyl;
  • Ring B is 4- to 10-membered heterocycloalkyl, 3- to 8-membered cycloalkyl, 5- to 6-membered heteroaryl, or phenyl;
  • each R^B is independently selected from the group consisting of:
  • halogen;
  • —OH;
  • oxo;
  • cyano;
  • —O(C₁-C₆ alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens;
  • —C(O)(C₁-C₆ alkyl);
  • —C(O)O(C₁-C₆ alkyl);
  • phenyl;
  • 5- to 6-membered heteroaryl;
  • 4- to 8-membered heterocycloalkyl;
  • 3- to 8-membered cycloalkyl;
  • —C(O)(3- to 8-membered cycloalkyl);
  • —C(O)(4-8-membered heterocycloalkyl);
  • —S(O)₂(C₁-C₆ alkyl);
  • —S(O)₂(3- to 8-membered cycloalkyl);
  • —C(O)NR^B1R^B2;
  • —S(O)₂NR^B1R^B2;
  • —NR^C1S(O)₂NR^B1R^B2;
  • —(C═N—R^C1)—NR^B1R^B2;
  • —NR^C1—(C═N—R^C1)—NR^B1R^B2;
  • —NR^C1—(C═N—CN)—NR^B1R^B2; and
  • C₁-C₆ alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of halogen, —OH, and —O(C₁-C₆ alkyl);
  • wherein R^C1, R^B1 and R^B2 are each independently hydrogen or C₁-C₆ alkyl;
  • m is 0, 1, 2, 3, or 4;
  • n is 0, 1, 2, 3, 4, or 5;
  • R^C is halogen, cyano, C₁-C₆ alkyl, OH, —O(C₁-C₆ alkyl), or 3- to 8-membered cycloalkyl; and
  • p is 0, 1, 2, 3, or 4;
  • wherein:
  • a) when L is a bond, ring B is selected from the group consisting of

• • b) when ring B is pyridin-4-yl and A is phenyl, R^D is selected from the group consisting of carbamoyl, chloro, hydroxymethyl, difluoromethyl, methoxy, and cyano; and
  • c) when L is —CH₂—CH₂—, n is 0, 1, or 2.
  • Enumerated Embodiment 2. The compound of Enumerated Embodiment 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is

• • Enumerated Embodiment 3. The compound of Enumerated Embodiment 1 or 2, or a pharmaceutically acceptable salt thereof, wherein R^D is halogen or —O(C₁-C₆ alkyl) optionally substituted with 1 to 3 independently selected halogens.
  • Enumerated Embodiment 4. The compound of any one of Enumerated Embodiments 1-3, or a pharmaceutically acceptable salt thereof, wherein R^D is halogen.
  • Enumerated Embodiment 5. The compound of any one of Enumerated Embodiments 1-4, or a pharmaceutically acceptable salt thereof, wherein R^D is fluorine.
  • Enumerated Embodiment 6. The compound of any one of Enumerated Embodiments 1-4, or a pharmaceutically acceptable salt thereof, wherein R^D is chlorine.
  • Enumerated Embodiment 7. The compound of Enumerated Embodiment 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is 5- to 6-membered heteroaryl optionally substituted with 1 to 4 R^A.
  • Enumerated Embodiment 8. The compound of any one of Enumerated Embodiment 1 or 7, or a pharmaceutically acceptable salt thereof, wherein Ring A is 5-membered heteroaryl optionally substituted with 1 to 4 R^A.
  • Enumerated Embodiment 9. The compound of any one of Enumerated Embodiments 1, 7, or 8, or a pharmaceutically acceptable salt thereof, wherein Ring A is oxazolyl, pyrazolyl, thiazolyl, isothiazolyl, or isoxazolyl, each of which is optionally substituted with 1 to 3 R^A.
  • Enumerated Embodiment 10. The compound of any one of Enumerated Embodiments 1, or 7-9, or a pharmaceutically acceptable salt thereof, wherein Ring A is oxazolyl optionally substituted with 1 to 2 R^A.
  • Enumerated Embodiment 11. The compound of any one of Enumerated Embodiments 1, or 7-10, or a pharmaceutically acceptable salt thereof, wherein Ring A is oxazol-5-yl optionally substituted with 1 to 2 R^A.
  • Enumerated Embodiment 12. The compound of Enumerated Embodiment 1 or 7, or a pharmaceutically acceptable salt thereof, wherein Ring A is 6-membered heteroaryl optionally substituted with 1 to 4 R^A.
  • Enumerated Embodiment 13. The compound of any one of Enumerated Embodiments 1, 7, or 12, or a pharmaceutically acceptable salt thereof, wherein Ring A is pyridinyl, pyridazinyl, or pyrimidinyl, each of which is optionally substituted with 1 to 4 R^A.
  • Enumerated Embodiment 14. The compound of any one of Enumerated Embodiments 1, 7, 12, or 13, or a pharmaceutically acceptable salt thereof, wherein Ring A is pyridinyl optionally substituted with 1 to 4 R^A.
  • Enumerated Embodiment 15. The compound of any one of Enumerated Embodiments 1, 7, or 12-14, or a pharmaceutically acceptable salt thereof, wherein Ring A is pyridin-4-yl optionally substituted with 1 to 4 R^A.
  • Enumerated Embodiment 16. The compound of any one of Enumerated Embodiments 1-15, wherein each R^A is independently selected from the group consisting of halogen and C₁-C₆ alkyl.
  • Enumerated Embodiment 17. The compound of any one of Enumerated Embodiments 1-16, or a pharmaceutically acceptable salt thereof, wherein Ring B is 4- to 8-membered heterocycloalkyl, 3- to 8-membered cycloalkyl, or 5- to 6-membered heteroaryl.
  • Enumerated Embodiment 18. The compound of any one of Enumerated Embodiments 1-17, or a pharmaceutically acceptable salt thereof, wherein Ring B is pyridinyl, piperazinyl, morpholinyl, piperidinyl, pyrrolidinyl, oxazolyl, or pyrazolyl.
  • Enumerated Embodiment 19. The compound of any one of Enumerated Embodiments 1-18, or a pharmaceutically acceptable salt thereof, wherein Ring B is pyridinyl, piperazinyl, morpholinyl, piperidinyl, or pyrrolidinyl.
  • Enumerated Embodiment 20. The compound of any one of Enumerated Embodiments 1-19, or a pharmaceutically acceptable salt thereof, wherein Ring B is

• • Enumerated Embodiment 21. The compound of any one of Enumerated Embodiments 1-20, or a pharmaceutically acceptable salt thereof, wherein each R^B is independently selected from the group consisting of:
  • halogen;
  • oxo;
  • —O(C₁-C₆ alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens;
  • C₁-C₆ alkyl optionally substituted with 1 to 5 substituents independently selected from halogen, —OH, and —O(C₁-C₆ alkyl);
  • —S(O)₂(C₁-C₆ alkyl);
  • —S(O)₂NR^B1R^B2;
  • —C(O)NR^B1R^B2;
  • —C(O)(C₁-C₆ alkyl);
  • 4- to 8-membered heterocycloalkyl; and
  • 5- to 6-membered heteroaryl.
  • Enumerated Embodiment 22. The compound of any one of Enumerated Embodiments 1-21, or a pharmaceutically acceptable salt thereof, wherein each R^B is independently selected from the group consisting of oxo, —C(O)(C₁-C₆ alkyl), —C(O)NR^B1R^B2, —S(O)₂(C₁-C₆ alkyl), —S(O)₂NR^B1R^B2, unsubstituted C₁-C₆ alkyl, 4- to 8-membered heterocycloalkyl, and 5- to 6-membered heteroaryl.
  • Enumerated Embodiment 23. The compound of any one of Enumerated Embodiments 1-22, or a pharmaceutically acceptable salt thereof, wherein each R^B is independently selected from the group consisting of oxo, —C(O)(C₁-C₃ alkyl), —C(O)N(Me)₂, —S(O)₂Me, —S(O)₂N(Me)₂, methyl, oxetanyl, and pyridinyl.
  • Enumerated Embodiment 24. The compound of any one of Enumerated Embodiments 1-23, or a pharmaceutically acceptable salt thereof, wherein L is a bond, C₁-C₆ alkylene, #—C(O)—N(R^L)—(C₁-C₆ alkylene)-$, #—C(O)—(C₁-C₆ alkylene)-$, or #—(C₁-C₆ alkylene)-C(O)—N(R^L)—(C₁-C₆ alkylene)-$, wherein #represents the attachment point to ring B, and $ represents the attachment point to the remainder of the molecule;
  • wherein each C₁-C₆ alkylene of L is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C₁-C₆ alkyl; and
  • wherein each R^L is independently hydrogen or C₁-C₆ alkyl.
  • Enumerated Embodiment 25. The compound of any one of Enumerated Embodiments 1-24, or a pharmaceutically acceptable salt thereof, wherein each C₁-C₆ alkylene of L is substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C₁-C₆ alkyl.
  • Enumerated Embodiment 26. The compound of any one of Enumerated Embodiments 1-25, or a pharmaceutically acceptable salt thereof, wherein each C₁-C₆ alkylene of L is substituted with 1 to 3 substituents independently selected from the group consisting of halogen and C₁-C₆ alkyl.
  • Enumerated Embodiment 27. The compound of any one of Enumerated Embodiments 1-26, or a pharmaceutically acceptable salt thereof, wherein each C₁-C₆ alkylene of L is substituted with 1 to 3 substituents independently selected from the group consisting of fluoro and methyl.
  • Enumerated Embodiment 28. The compound of any one of Enumerated Embodiments 1-24, or a pharmaceutically acceptable salt thereof, wherein each C₁-C₆ alkylene of L is unsubstituted.
  • Enumerated Embodiment 29. The compound of any one of Enumerated Embodiments 1-24, or a pharmaceutically acceptable salt thereof, wherein L is a bond, C₁-C₃ alkylene, or #—C(O)—N(R^L)—(C₁-C₃ alkylene)-$, wherein #represents the attachment point to ring B, and $ represents the attachment point to the remainder of the molecule; wherein each C₁-C₆ alkylene of L is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C₁-C₆ alkyl; and wherein each R^L is independently hydrogen or C₁-C₆ alkyl.
  • Enumerated Embodiment 30. The compound of any one of Enumerated Embodiments 1-24 or 29, or a pharmaceutically acceptable salt thereof, wherein L is a bond, —CH₂—, —CH₂CH₂—, or

• • Enumerated Embodiment 31. The compound of any one of Enumerated Embodiments 1-6 or 16-30, or a pharmaceutically acceptable salt thereof, wherein m is 1.
  • Enumerated Embodiment 32. The compound of any one of Enumerated Embodiments 1-6 or 17-30, or a pharmaceutically acceptable salt thereof, wherein m is 0.
  • Enumerated Embodiment 33. The compound of any one of Enumerated Embodiments 1-32, or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, or 2.
  • Enumerated Embodiment 34. The compound of any one of Enumerated Embodiments 1-33, or a pharmaceutically acceptable salt thereof, wherein R^C is fluoro.
  • Enumerated Embodiment 35. The compound of any one of Enumerated Embodiments 1-34, or a pharmaceutically acceptable salt thereof, wherein p is 0.
  • Enumerated Embodiment 36. A compound selected from the group consisting of compounds of Table 1, or a pharmaceutically acceptable salt thereof.
  • Enumerated Embodiment 37. A pharmaceutical composition comprising a compound according to any one of Enumerated Embodiments 1-36, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
  • Enumerated Embodiment 38. A method of treating a disease or condition mediated by NAMPT activity in a subject in need thereof, comprising administering to the subject a compound of any one of Enumerated Embodiments 1-36, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of Enumerated Embodiment 37.
  • Enumerated Embodiment 39. The method of Enumerated Embodiment 38, wherein the disease or condition is selected from the group consisting of cancer, a hyperproliferative disease or condition, an inflammatory disease or condition, a metabolic disorder, a cardiac disease or condition, chemotherapy induced tissue damage, a renal disease, a metabolic disease, a neurological disease or injury, a neurodegenerative disorder or disease, diseases caused by impaired stem cell function, diseases caused by DNA damage, primary mitochondrial disorders, and a muscle disease or muscle wasting disorder.
  • Enumerated Embodiment 40. The method of Enumerated Embodiment 38, wherein the disease or condition is selected from the group consisting of obesity, atherosclerosis, insulin resistance, type 2 diabetes, cardiovascular disease, Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, depression, Down syndrome, neonatal nerve injury, aging, axonal degeneration, carpal tunnel syndrome, Guillain-Barre syndrome, nerve damage, polio (poliomyelitis), and spinal cord injury.

General Synthetic Methods

Compounds of Formula (I), or any variation or embodiment thereof, or a salt of any of the foregoing, will now be described by reference to illustrative synthetic schemes for their general preparation below and the specific examples that follow. Artisans will recognize that, to obtain the various compounds herein, starting materials may be suitably selected so that the ultimately desired substituents will be carried through the reaction scheme with or without protection as appropriate to yield the desired product. Alternatively, it may be necessary or desirable to employ, in the place of the ultimately desired substituent, a suitable group that may be carried through the reaction scheme and replaced as appropriate with the desired substituent. In addition, one of skill in the art will recognize that protecting groups may be used to protect certain functional groups (amino, carboxy, or side chain groups) from reaction conditions, and that such groups are removed under standard conditions when appropriate. Unless otherwise specified, the variables are as defined above in reference to Formula (I).

Where it is desired to obtain a particular enantiomer of a compound, this may be accomplished from a corresponding mixture of enantiomers using any suitable conventional procedure for separating or resolving enantiomers. Thus, for example, diastereomeric derivatives may be produced by reaction of a mixture of enantiomers, e.g. a racemate, and an appropriate chiral compound. The diastereomers may then be separated by any convenient means, for example by crystallization and the desired enantiomer recovered. In another resolution process, a racemate may be separated using chiral High Performance Liquid Chromatography. Alternatively, if desired a particular enantiomer may be obtained by using an appropriate chiral intermediate in one of the processes described.

Chromatography, recrystallization and other conventional separation procedures may also be used with intermediates or final products where it is desired to obtain a particular isomer of a compound or to otherwise purify a product of a reaction.

General methods of preparing compounds described herein are depicted in exemplified methods below. Variable groups in the schemes provided herein are defined as for Formula (I), or any variation thereof. Other compounds described herein may be prepared by similar methods.

In some embodiments, compounds provided herein may be synthesized according to Schemes A1, A2, A3 or A4, wherein Ring A, Ring B, L, R^B, R^C, n, and p are as defined for formula (I) or any variation thereof detailed herein.

In certain embodiments compounds provided herein may be synthesized according to Scheme Ala, A2a, A3a or A4a, wherein Ring A, Ring B, L, R^B, R^C, n, and p are as defined for formula (I) or any variation thereof detailed herein.

Particular non-limiting examples are provided in the Example section below.

EXAMPLES

The following examples are offered to illustrate but not to limit the compositions, uses, and methods provided herein. The compounds are prepared using the general methods described above or below. Starting materials were either purchased from commercial source or prepared according to literature procedures.

The following abbreviations are used throughout the Examples: TEA (triethylamine), DCM (dichloromethane), (Boc)₂O (di-tert-butyl decarbonate), EA (Ethyl acetate), PE (Petroleum ether, DMF (N,N-dimethylformamide), DIEA (N-ethyl-N-isopropylpropan-2-amine), DMAP [4-(dimethylamino)pyridine], HATU (1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate), HOAt (1-Hydroxy-7-azabenzotriazole), HOBt (Hydroxybenzotriazole), EDCI (1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide), MeOH (methanol), EtOH (ethanol), iPrOH (propan-2-ol), ACN (acetonitrile), TFA (trifluoroacetic acid), DPPA (Diphenylphosphoryl azide), DBU (1,8-Diazabicyclo(5.4.0)undec-7-ene), THF (tetrahydrofuran), PPh₃ (triphenylphosphine), SM (starting material), Hex (hexane), NCS (N-chlorosuccinimide), r.t. or rt (room temperature around 21 to 24° C.), DCE (dichloroethane), FA (formic acid), CHCl₃ (chloroform), BnBr (benzyl bromide), HCl (hydrogen chloride), equiv (equivalent), and DSC (bis(2,5-dioxopyrrolidin-1-yl) carbonate), HBTU (O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate).

Aniline Syntheses

Example A

Synthesis of Aniline Intermediates 1.1, 1.2, and 1.3

Step 1: Synthesis of tert-butyl (S)-(4-(1-cyclobutyl-5-oxopiperazin-2-yl)phenyl)carbamate

Ketone (252 mg, 3.6 mmol) and acetic acid (108 mg, 1.8 mmol) were added to a stirring solution of tert-butyl (S)-(4-(5-oxopiperazin-2-yl)phenyl)carbamate (Ref. 1) (252 mg, 1.8 mmol) in CH₂Cl₂ (5 mL) at r.t. and the reaction stirred for 30 min. Sodium triacetoxyborohydride (763 mg, 3.6 mmol) was added and the reaction was stirred for 2 h before being confirmed complete by LCMS. The reaction was then quenched with saturated sodium bicarbonate (15 mL), extracted with CH₂Cl₂ (3×15 mL), organic solutions were combined, dried over sodium sulfate, filtered, and solvent removed by rotary evaporation. The crude material was carried forward without additional purification. LRMS (ES) m/z: 346.1 [M+H]⁺.

Step 2: Synthesis of (S)-5-(4-aminophenyl)-4-cyclobutylpiperazin-2-one

HCl (4M in dioxanes, 2.5 mL, 10 mmol) was added to a stirring solution of tert-butyl (S)-(4-(1-methyl-5-oxopiperazin-2-yl)phenyl)carbamate (1.8 mmol) at r.t. After 6 h, the reaction was concentrated by rotary evaporation, triturated with EtOAc, filtered, and the resultant solid dried under high vacuum to give the desired product as an off-white solid (400 mg, 70% over 2 steps). LCMS-APCI (POS.) m/z: 246.1 [M+H]⁺.

Compounds in the following table were prepared in a similar manner as intermediate 1.1, using the intermediates and reagents as listed.

Intermediate	Reagents	Structure, Name and Data
1.2	oxetan-3-one
		Intermediate 1.2: (S)-5-(4-aminophenyl)-4-
		(oxetan-3-yl)piperazin-2-one. LCMS-ESI
		(POS.) m/z: 248.1 [M + H]+.
1.3	acetone
		Intermediate 1.3: (S)-5-(4-aminophenyl)-4-
		isopropylpiperazin-2-one. LCMS-APCI
		(POS.) m/z: 234.1 [M + H]+.
1.4	fomaldehyde
		Intermediate 1.4: (S)-5-(4-aminophenyl)-4-
		methylpiperazin-2-one. LCMS-ESI (POS.)
		m/z: 206.1 [M + H]+.

Example B

Synthesis of Aniline Intermediate 2.1

Step 1: Synthesis of tert-butyl (E)-4-(4-nitrostyryl)piperidine-1-carboxylate

To a solution of tert-butyl 4-vinylpiperidine-1-carboxylate (5.71 g, 27 mmol, 1.80 equiv), 1-iodo-4-nitrobenzene (3.74 g, 15 mmol, 1.00 equiv), triethylamine (4.55 g, 45 mmol, 3.00 equiv) in DMF (50 mL) was added bis[tri(o-tolyl)phosphine]palladium(II) chloride (0.59 g, 0.75 mmol, 0.05 equiv). The reaction mixture was degassed for 10 min. Then it was heated at 130° C. for 24 h. The reaction mixture was extracted with ether/EtOAc (50 mL/50 mL) and H₂O (80 mL). The organic layer was concentrated and the residue was purified on silica gel with 35% EtOAc/Hex to give the desired product tert-butyl (E)-4-(4-nitrostyryl)piperidine-1-carboxylate as a yellow-reddish solid (1.70 g, 34%). LRMS (ES) m/z: 333 [M+H]⁺.

Step 2: Synthesis of tert-butyl 4-(4-aminophenethyl)piperidine-1-carboxylate

To a solution tert-butyl (E)-4-(4-nitrostyryl)piperidine-1-carboxylate (0.83 g, 2.50 mmol) in MeOH (30 mL) was added 10% Pd/C (0.27 g). The reaction mixture was stirred under H₂ at 60 psi for 30 min. The catalyst was filtered off and the filtrate was concentrated to give the desired product tert-butyl 4-(4-aminophenethyl)piperidine-1-carboxylate as a yellowish solid (0.70 g, 92%). LRMS (ES) m/z: 305 [M+H]⁺.

Example C

Synthesis of Aniline Intermediate 3.1

Step 1: Synthesis of tert-butyl (4-acetylphenyl)carbamate

To a solution of 1-(4-aminophenyl)ethanone (2.70 g, 20 mmol, 1.00 equiv) in dry dioxane (14 mL) was added Boc₂O (5.24 g, 24 mmol, 1.20 equiv). The resulting mixture was heated at 100° C. for 5 h. The solvent was evaporated, and the residue was taken up in EtOAc (100 mL). The organic layer was washed with 1 M HCl (30 mL) three times and then brine (50 mL), dried over Na₂SO₄, and evaporated to afford the desired product tert-butyl (4acetylphenyl)carbamate as a white solid (3.60 g, 77%). LRMS (ES) m/z: 236 [M+H]⁺.

Step 2: Synthesis of tert-butyl (4-(1-hydroxy-1-(pyridin-4-yl)ethyl)phenyl)carbamate

To a solution of tert-butyl (4acetylphenyl)carbamate (3.53 g, 15 mmol, 2.00 equiv) in MTBE (30 mL) was added 4-cyanopyridine (0.78 g, 7.50 mmol, 1.00 equiv) and bis-(pinacolato)diboron (4.57 g, 18 mmol, 2.40 equivalents). The resulting mixture was heated at 90° C. for 16 h. The reaction was cooled down to rt and quenched with Na₂CO₃ solution (2 M, 50 mL) and stirred under air for 15 minutes. Brine (30 mL) was added. Then the reaction mixture was extracted with EtOAc (3×50 mL). The organic layer was dried over Na₂SO₄, concentrated, and purified on silica gel to afford the desired product tert-butyl (4-(1-hydroxy-1-(pyridin-4-yl)ethyl)phenyl)carbamate as a white solid (0.70 g, 30%). LRMS (ES) m/z: 315 [[M+H]⁺.

Step 3: Synthesis of 1-(4-aminophenyl)-1-(pyridin-4-yl)ethan-1-ol

To a solution of tert-butyl (4-(1-hydroxy-1-(pyridin-4-yl)ethyl)phenyl)carbamate (0.69 g, 2.20 mmol, 1.00 equiv) in MeOH (1 mL) was added 4N HCl/dioxane (5.50 mL, 22 mmol, 10 equiv) at 0° C. The reaction mixture was stirred at rt for 16 h. The solvents were removed and the residue was used directly in the next step. LRMS (ES) m/z: 215 [M+H]⁺.

Example D

Synthesis of Aniline Intermediates 4.1, 4.2, 4.3 and 4.4

Step 1: Preparation of tert-butyl 4-[(4-nitrophenyl)methoxy]piperidine-1-carboxylate

To a solution of silver (I) oxide (4.61 g, 19.87 mmol, 2.0 eq) and TBAI (0.37 g, 0.99 mmol, 0.1 eq) in DCM (10 mL) was added tert-butyl 4-hydroxypiperidine-1-carboxylate (2.0 g, 9.94 mmol, 1.0 eq). Nitrobenzyl bromide (4.29 g, 19.87 mmol, 2.0 eq) was added and the reaction was stirred at 45° C. for 1 h while shielded from light. The crude mixture was filtered over Celite, washed with DCM, and concentrated under reduced pressure. The residue brown oil was used directly in the next step without purification. Assume quantitative yield (3.34 g, 9.94 mmol, quantitative yield). LCMS-APCI (POS.) m/z: 237.1 [M+H-Boc]⁺. 1H NMR (400 MHz, DMSO-d6) δ 8.25 (dd, J=8.9, 2.1 Hz, 2H), 7.68 (d, J=8.7 Hz, 2H), 4.77 (s, 2H), 3.65 (ddt, J=13.2, 8.6, 4.2 Hz, 4H), 2.95 (s, 2H), 1.68 (dt, J=13.1, 4.0 Hz, 2H), 1.58 (s, 1H), 1.39 (s, 9H).

Step 2: Preparation of 4-[(4-aminophenyl)methoxy]piperidin-1-yl 2,2-dimethylpropanoate

Tert-butyl 4-[(4-nitrophenyl)methoxy]piperidine-1-carboxylate (3.34 g, 9.94 mmol, 1.0 eq) and palladium on carbon (1.06 g, 0.99 mmol, 0.2 eq) were suspended in methanol (10 mL) and stirred under hydrogen (50 psi) at r.t. for 1 h. The reaction mixture was filtered through Celite, concentrated, and purified with flash chromatography over silica gel (0-20% MeOH:DCM w/0.1% triethylamine). The product was isolated as a brown oil (1.357 g, 4.429 mmol, 44.6% yield over two steps). LCMS-APCI (POS.) m/z: 207.1 (M+H-Boc)⁺. 1H NMR (400 MHz, Methanol-d4) δ 7.09-7.05 (m, 2H), 6.72-6.67 (m, 2H), 6.64 (d, J=8.1 Hz, 1H), 4.35 (s, 2H), 3.82 (dt, J=13.6, 4.8 Hz, 3H), 3.75 (dq, J=8.6, 4.3 Hz, 2H), 3.03 (s, 3H), 1.81 (dt, J=10.3, 3.0 Hz, 3H), 1.45 (s, 3H), 1.38 (ddd, J=13.2, 8.9, 3.9 Hz, 3H).

Compounds in the following table were prepared in a similar manner as intermediate 4.1, using the starting material as listed.

	Starting
Intermediate	Material	Structure, Name and Data
4.2	tert-butyl 3- hydroxyaz- etidine-1- carboxylate
		tert-butyl 3-((4-aminobenzyl)oxy)azetidine-1-carboxylate. ).
		LCMS-APCI (POS.) m/z: 179.1 [M + H − Boc]+. 1H NMR (400
		MHz, Methanol-d4) δ 7.08 (d, J = 7.9 Hz, 2H), 6.70 (d, J = 7.9
		Hz, 2H), 4.34 (s, 2H), 4.31 (s, 1H), 4.01 (t, J = 8.0 Hz, 2H), 3.70
		(dd, J = 9.6, 4.1 Hz, 2H), 1.42 (s, 9H).
4.3	1-(oxetan- 3- yl)piperidin- 4-ol
		4-({[1-(oxetan-3-yl)piperidin-4-yl]oxy}methyl)aniline.
		LCMS-APCI (POS.) m/z: 263.1 [M + H − Boc]+. 1H NMR (400
		MHz, Methanol-d4) δ 7.10 (d, J = 8.0 Hz, 2H), 6.71 (d, J = 7.9
		Hz, 2H), 4.78 (t, J = 7.5 Hz, 3H), 4.71 (d, J = 6.8 Hz, 2H), 4.42
		(s, 2H), 4.04 (d, J = 8.9 Hz, 1H), 3.66 (s, 1H), 2.98 (t, J = 10.5
		Hz, 2H), 2.73 (s, 2H), 1.97 (d, J = 10.4 Hz, 3H), 1.87 (s, 2H).
4.4	1-(4- hydroxy- piperidin-1- yl)ethan-1- one
		1-(4-((4-aminobenzyl)oxy)piperidin-1-yl)ethan-1-one.
		1H NMR (400 MHz, Methanol-d4) δ 7.09 (d, J = 7.8 Hz, 2H),
		6.70 (d, J = 7.9 Hz, 2H), 4.42 (s, 2H), 3.89 (dt, J = 12.2, 4.6 Hz,
		1H), 3.76-3.62 (m, 2H), 3.25 (t, J = 8.8 Hz, 1H), 2.08 (s, 3H),
		1.95-1.78 (m, 3H), 1.64-1.37 (m, 3H).

Example E

Synthesis of Intermediates 5.1 to 5.5

Step 1: Synthesis of (R)-1-(4-nitrobenzyl)-5-(pyridin-3-yl)pyrrolidin-2-one

To a suspension of (5R)-5-(pyridin-3-yl)pyrrolidin-2-one (80 mg, 0.493 mmol) in THF (1.5 mL) was added lithium bis(trimethylsilyl)amide (83 mg, 0.49 mmol) at 0° C., then stirred at room temperature for 1 h. The mixture was cooled to 0° C., and the solution of 4-nitrobenzyl bromide (109 mg, 0.503 mmol) in THF (1 mL) was added at 0° C. The mixture was allowed to warm to room temperature and stirred for 4.5 h. The mixture was filtered and purified by reverse phase HPLC (0-50% MeCN/H₂O, 0.1% HCOOH) to give (5R)-1-[(4-nitrophenyl)methyl]-5-(pyridin-3-yl)pyrrolidin-2-one (22 mg, 15% yield). LCMS-APCI (POS.) m/z: 298.1 [M+H]⁺.

Step 2: Synthesis of (R)-1-(4-aminobenzyl)-5-(pyridin-3-yl)pyrrolidin-2-one

The mixture of (5R)-1-[(4-nitrophenyl)methyl]-5-(pyridin-3-yl)pyrrolidin-2-one (22 mg, 0.078 mmol) and platinum oxide (5 mg) in THF/MeOH (2 mL:1 mL) was stirred at r.t. under hydrogen (50 psi) for 3 h. The mixture was concentrated to give (5R)-1-[(4-nitrophenyl)methyl]-5-(pyridin-3-yl)pyrrolidin-2-one (15 mg), which was used for the next step without further purification. LCMS-APCI (POS.) m/z: 268.1 [M+H]⁺.

Intermediates in the following table were prepared in a similar manner as intermediate 5.1, using the starting material and reagents as listed.

	Starting
Intermediate	Material	Structure, Name and Data
5.2	2- azabicyclo [3.1.0] hexan-3-one
		Intermediate 5.2: 2-(4-aminobenzyl)-2-
		azabicyclo[3.1.0]hexan-3-one. LCMS-ESI
		(POS.) m/z: 203.1 [M + H]+.
5.3	5- azaspiro[2.4] heptan- 4-one
		Intermediate 5.3: 5-(4-aminobenzyl)-5-
		azaspiro[2.4]heptan-4-one. LCMS-ESI
		(POS.) m/z: 217.1 [M + H]+.
5.4	3,3- dimethyl- pyrrolidin-2- one
		Intermediate 5.4: 1-(4-aminobenzyl)-3,3-
		dimethylpyrrolidin-2-one. LCMS-ESI
		(POS.) m/z: 219.1 [M + H]+.
5.5	3- azabicyclo [3.1.0] hexan-2-one
		Intermediate 5.5: 3-(4-aminobenzyl)-3-
		azabicyclo[3.1.0]hexan-2-one. LCMS-ES
		(Pos) m/z:203.1 [M + H]+.

Example R

Synthesis of Intermediates 27.1 to 27.3

Step 1: Synthesis of tert-butyl 6-(((trifluoromethyl)sulfonyl)oxy)-2-azaspiro[3.3]hept-5-ene-2-carboxylate

To a solution of tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate (5 g, 1 equiv) in THF (200 mL, 0.118 M) at −78° C. was added lithium bis(trimethylsilyl)amide (71 mL, 1 M, 3 equiv) dropwise, the mixture was stirred at −78° C. for 1 h, followed by addition of phenyl triflimide (16.9 g, 2 equiv) in THF (100 mL) dropwise. The mixture was stirred for 3 h and quenched with water. The organic portion was concentrated, diluted with water, and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (0-20% EtOAc/Hexane gradient) to afford tert-butyl 6-(((trifluoromethyl)sulfonyl)oxy)-2-azaspiro[3.3]hept-5-ene-2-carboxylate (4.7 g, 57.8% yield). LRMS (ES) 288.1 [M+H-Bu]⁺.

Step 2: Preparation of tert-butyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-azaspiro[3.3]hept-5-ene-2-carboxylate

To a solution of tert-butyl 6-(((trifluoromethyl)sulfonyl)oxy)-2-azaspiro[3.3]hept-5-ene-2-carboxylate (2.7 g, 1 equiv) and potassium acetate (2 equiv) in dioxane (22 mL) was added 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (1.3 equiv) and PdCl₂dppf (0.1 equiv), the mixture was stirred at 80° C. for 2 hour until reaction completed, the mixture was cooled, filtered through Celite, concentrated, and purified by silica gel chromatography (0-10% EtOAc/Hexanes gradient) to afford tert-butyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-azaspiro[3.3]hept-5-ene-2-carboxylate (1.8 g, 69.6% yield). LRMS (ES) 266.1 [M+H-Bu]⁺.

Step 3: Preparation of tert-butyl 6-(2-fluoro-4-nitrophenyl)-2-azaspiro[3.3]hept-5-ene-2-carboxylate

To a solution of tert-butyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-azaspiro[3.3]hept-5-ene-2-carboxylate (1.8 g, 1 equivequiv) and 1-bromo-2-fluoro-4-nitrobenzene (1.5 equivequiv) in DMF (30 mL), was added potassium carbonate (2 equiv) and PdCl₂dppf (0.1 equiv). The mixture was stirred at 80° for 2 hour until reaction completed, the mixture was cooled, filtered through Celite, concentrated and purified by silica gel chromatography (0-10% EtOAc/Hexanes gradient) to afford tert-butyl 6-(2-fluoro-4-nitrophenyl)-2-azaspiro[3.3]hept-5-ene-2-carboxylate (1.4 g, 74.8% yield) as a yellow solid. LRMS (ES) 279.1 [[M+H-Bu]⁺. ¹H NMR (400 MHz, DMSO-d₆) δ 8.14 (dd, J=10.5, 2.2 Hz, 1H), 8.10 (dd, J=8.5, 2.3 Hz, 1H), 7.59 (t, J=8.1 Hz, 1H), 6.79 (d, J=3.1 Hz, 1H), 4.12-4.03 (m, 4H), 3.07 (s, 2H), 1.39 (s, 9H).

Step 4: Preparation of tert-butyl 6-(4-amino-2-fluorophenyl)-2-azaspiro[3.3]heptane-2-carboxylate

A solution of tert-butyl 6-(2-fluoro-4-nitrophenyl)-2-azaspiro[3.3]hept-5-ene-2-carboxylate (1.4 g, 1 equiv) in methanol (8 mL) and dioxane (8 mL) was purged under nitrogen for 5 minutes, followed by addition of Pd/C (0.31 equiv) slowly and purged for an additional 5 minutes. The mixture was filled with a balloon full of hydrogen, stirred at 24° C. for 16 h, filtered through Celite and concentrated to afford tert-butyl 6-(4-amino-2-fluorophenyl)-2-azaspiro[3.3]heptane-2-carboxylate (1.3 g, 99.6% yield). LRMS (ES) 251.1 [[M+H-Bu]⁺. ¹H NMR (400 MHz, DMSO-d₆) δ 6.90 (t, J=8.6 Hz, 1H), 6.32 (dd, J=8.3, 2.1 Hz, 1H), 6.24 (dd, J=13.0, 2.2 Hz, 1H), 5.18 (s, 2H), 3.95 (s, 2H), 3.73 (s, 2H), 3.36-3.26 (m, 1H), 2.43 (td, J=8.6, 2.9 Hz, 2H), 2.16 (td, J=9.5, 3.0 Hz, 2H), 1.37 (s, 9H).

Intermediate anilines in the following table were prepared in a similar manner as Intermediate 27.1, using the starting material and reagents as listed.

Inter-	Starting Material
mediate	And Reagents	Structure, Name and Data
27.2	tert-butyl 6-oxo-2- azaspiro[3.3] heptane- 2-carboxylate 1-bromo-4- nitrobenzene
		Intermediate 27.2: Tert-butyl 6-(4-
		aminophenyl)-2-azaspiro[3.3]heptane-2-
		carboxylate
		LCMS-ES (POS.) m/z: 231.1 [M + H − Bu]+.
27.3	tert-butyl 2-oxo-6- azaspiro[3.4] octane-6- carboxylate 1-bromo-2- fluoro-4- nitrobenzene
		Intermediate 27.3: tert-butyl 2-(4-amino-2-
		fluorophenyl)-6-azaspiro[3.4]octane-6-
		carboxylate
		LCMS-ES (POS.) m/z: 265.1 [M + H − Bu]+.

Example S

Synthesis of Intermediates 28.1 to 27.8

Step 1: Synthesis of diethyl (2-fluoro-4-nitrobenzyl)phosphonate

1-(bromomethyl)-2-fluoro-4-nitrobenzene (3.01 g, 1 equiv) was mixed with triethyl phosphite (2 equiv) and the resulting solution was stirred at 120° C. for 40 minutes, cooled and purified by silica gel chromatography (10-100%% EtOAc/Hexanes gradient) to afford diethyl (2-fluoro-4-nitrobenzyl)phosphonate (3.37 g, 89.8% yield) as a yellow oil. LRMS (ES) 292.1 [M+H]. ¹H NMR (400 MHz, DMSO-d₆) δ 8.15-8.06 (m, 2H), 7.69-7.63 (m, 1H), 4.03-3.97 (m, 4H), 3.42 (dd, J=22.2, 1.2 Hz, 2H), 1.23-1.16 (m, 6H).

Step 2: Synthesis of tert-butyl 6-(2-fluoro-4-nitrobenzylidene)-2-azaspiro[3.3]heptane-2-carboxylate

To a solution of diethyl (2-fluoro-4-nitrobenzyl)phosphonate (2.2 g, 1 equiv) in THF (20 mL), was added tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate (2 equiv) at 24° C., and sodium hydride (4 equiv) slowly at 0° C., the mixture was stirred at 0° C. for 1 h, slowly quenched with ice and water, and extracted with DCM. The combined organic layers were dried over sodium sulfate, concentrated and purified by silica gel chromatography (0-20% EtOAc/Hexanes gradient) to afford tert-butyl 6-(2-fluoro-4-nitrobenzylidene)-2-azaspiro[3.3]heptane-2-carboxylate (0.31 g, 11.6% yield) as a yellow oil. LRMS (ES) 393.2 [M+H-Bu]⁺.

Step 3: Preparation of tert-butyl 6-(4-amino-2-fluorobenzyl)-2-azaspiro[3.3]heptane-2-carboxylate

A solution of tert-butyl 6-(2-fluoro-4-nitrobenzylidene)-2-azaspiro[3.3]heptane-2-carboxylate (0.85 g, 1 equiv) in methanol (6 mL) and dioxane (6 mL) was purged under nitrogen for 5 minutes, added Pd (0.42 equiv) slowly, purged for an additional 5 minutes. The mixture was filled with a balloon full of hydrogen and stirred at 24° C. for 4 h, filtered through Celite and concentrated to afford tert-butyl 6-(4-amino-2-fluorobenzyl)-2-azaspiro[3.3]heptane-2-carboxylate (0.72 g, 92.8% yield). LRMS (ES) 265.1 [M+H-Bu]⁺.

Intermediate anilines in the following table were prepared in a similar manner as described above, using the starting material and reagents as listed.

Intermediate	Starting Material	Structure, Name and Data
28.2	tert-butyl 2-oxo-6- azaspiro[3.4]octane-6- carboxylate 1-(bromomethyl)-2- fluoro-4-nitrobenzene
		Intermediate 28.2: tert-butyl 2-(4-amino-2-
		fluorobenzyl)-6-azaspiro[3.4]octane-6-
		carboxylate
		LCMS-ES (POS.) m/z: 279.1 [M + H − Bu]+.
		1H NMR (400 MHz, DMSO-d6) δ 6.83 (t, J =
		8.6 Hz, 1H), 6.31-6.22 (m, 2H), 5.13 (s, 2H),
		3.24-3.11 (m, 3H), 3.08 (d, J = 4.1 Hz, 1H),
		2.48 (s, 1H), 2.45-2.30 (m, 1H), 2.01-1.85
		(m, 2H), 1.84-1.57 (m, 4H), 1.37 (s, 9H), 1.22
		(s, 1H).
28.3	tert-butyl 8-oxo-3- azabicyclo[3.2.1]octane- 3-carboxylate 1-(bromomethyl)-4- nitrobenzene
		Intermediate 28.3: tert-butyl 8-(4-
		aminobenzyl)-3-azabicyclo[3.2.1]octane-3-
		carboxylate
28.4	tert-butyl 6-oxo-3- azabicyclo[3.1.1]heptane- 3-carboxylate 1-(bromomethyl)-4- nitrobenzene
		Intermediate 28.4: tert-butyl 6-(4-
		aminobenzyl)-3-azabicyclo[3.1.1]heptane-3-
		carboxylate
28.5	tert-butyl 7-oxo-4- azaspiro[2.5]octane-4- carboxylate 1-(bromomethyl)-4- nitrobenzene
		Intermediate 28.5: tert-butyl 7-(4-
		aminobenzyl)-4-azaspiro[2.5]octane-4-
		carboxylate
28.6	tert-butyl 5-oxo-2- azabicyclo[4.1.0]heptane- 2-carboxylate 1-(bromomethyl)-4- nitrobenzene
		Intermediate 28.6: tert-butyl 5-(4-
		aminobenzyl)-2-azabicyclo[4.1.0]heptane-2-
		carboxylate
28.7	tert-butyl 4-(2-fluoro-4- nitrobenzyl)piperidine-1- carboxylate 1-(bromomethyl)-2- fluoro-4-nitrobenzene
		Intermediate 28.7: tert-butyl 4-(4-amino-2-
		fluorobenzyl)piperidine-1-carboxylate
28.8	tert-butyl 3-oxo-8- azabicyclo[3.2.1]octane- 8-carboxylate 1-(bromomethyl)-4- nitrobenzene
		Intermediate 28.8: tert-butyl 3-(4-
		aminobenzyl)-8-azabicyclo[3.2.1]octane-8-
		carboxylate
		LCMS-ES (POS.) m/z: 261.1 [M + H − Boc]+.

Carbamate Synthesis

Method 1: Synthesis of Carbamate from Aniline and Chloroformate

Example F

Preparation of 4-chlorobenzyl (4-((4-methyl-2-oxopiperazin-1-yl)methyl)phenyl)carbamate (Compound 28)

To a mixture of aniline (88 mg, 0.40 mmol) in DCM (2 mL) was added DIEA (104 mg, 0.80 mmol), N,N-dimethylaniline (DMAP, 23 mg, 0.20 mmol) followed by 4-C₁-benzyl chloroformate (98 mg, 0.48 mmol). The reaction mix was stirred overnight and concentrated to dryness. The residue was purified on Agilent RP-HPLC on a Phenomenex, Gemini 5u C18 150×21.2 mm column eluting with a gradient of 10% ACN/Water to 100% ACN/Water over 40 min to give the desire product (40 mg, yield 65%) as an off-white solid. LRMS (ES) m/z: 388.1 [M+H]⁺. ¹H NMR (400 MHz, Methanol-d4) δ 7.47-7.24 (m, 6H), 7.22 (d, J=8.3 Hz, 2H), 5.17 (s, 2H), 4.57 (s, 2H), 3.34-3.26 (m, 2H), 3.17 (s, 2H), 2.68 (t, J=5.6 Hz, 2H), 2.35 (s, 3H).

Compounds in the following table were prepared in a similar manner as Compound 28, using the aniline as listed. Aniline intermediates were either purchased from commercial source or prepared according to above or to the procedures of published patent application WO 2021/159015.

Co#	Aniline	Structure, Name and Data
172	4-(pyridin-3- ylmethyl)aniline
		Compound 172: 4-chlorobenzyl (4-(pyridin-3-
		ylmethyl)phenyl)carbamate. LRMS (ES) m/z: 353.1 [[M + H]+.
		1H NMR (400 MHz, Methanol-d4) δ 8.44 (s, 1H), 7.67 (d, J = 7.9
		Hz, 1H), 7.38 (t, J = 7.7 Hz, 8H), 7.15 (d, J = 8.1 Hz, 2H), 5.16 (s,
		2H), 3.98 (s, 2H).
216	4-(pyridin-4- ylmethyl)aniline
		Compound 216: 4-chlorobenzyl (4-(pyridin-4-
		ylmethyl)phenyl)carbamate.
		LRMS (ES) m/z: 353.1 [M + H]+. 1H NMR (400 MHz, DMSO-d6)
		δ 9.75 (s, 1 H), 8.44 (d, J = 4.9 Hz, 2 H), 7.45 (s, 4 H), 7.39 (d, J =
		8.2 Hz, 2 H), 7.21 (d, J = 5.1 Hz, 2 H), 7.16 (d, J = 8.2 Hz, 2 H),
		5.13 (s, 2 H), 3.89 (s, 2 H).
233	4-(pyridin-2- ylmethyl)aniline
		Compound 233: 4-chlorobenzyl (4-(pyridin-2-
		ylmethyl)phenyl)carbamate. LRMS (ES) m/z: 353.1 [M + H]+.
		1H NMR (400 MHz, Methanol-d4) δ 8.49-8.42 (m, 1H), 7.76 (td,
		J = 7.7, 1.8 Hz, 1H), 7.40 (dd, J = 15.3, 9.2 Hz, 6H), 7.27 (dd, J =
		10.6, 6.8 Hz, 2H), 7.18 (d, J = 8.2 Hz, 2H), 5.16 (s, 2H), 4.10 (s,
		2H).
307	4-benzylaniline
		Compound 307: 4-chlorobenzyl (4-(pyridin-3-
		ylmethyl)phenyl)carbamate. LRMS (ES) m/z: 352.1 [M + H]. 1H
		NMR (400 MHz, Methanol-d4) δ 7.40 (d, J = 5.9 Hz, 1H), 7.41-
		7.19 (m, 6H), 7.22-7.08 (m, 6H), 5.16 (s, 2H), 3.92 (s, 2H).
236	1.1
		Compound 236: 4-chlorobenzyl (S)-(4-(1-cyclobutyl-5-
		oxopiperazin-2-yl)phenyl)carbamate. LRMS (ES) m/z: 414.1
		[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 7.48-7.25 (m, 8H),
		5.16 (s, 2H), 3.66-3.50 (m, 2H), 3.44-3.34 (m, 1H), 3.06-2.88
		(m, 2H), 2.00-1.88 (m, 2H), 1.75-1.40 (m, 4H), 1.29 (qd, J =
		7.0, 3.2 Hz, 1H).
346	1.2
		Compound 346: 4-chlorobenzyl (S)-(4-(1-(oxetan-3-yl)-5-
		oxopiperazin-2-yl)phenyl)carbamate. LRMS (ES) m/z: 416.1
		[M + H]+. 1H NMR (400 MHz, Chloroform-d) δ 7.39 (d, J = 17.3
		Hz, 1H), 7.35 (s, 4H), 7.35-7.20 (m, 2H), 6.92 (s, 1H), 5.17 (s,
		2H), 4.64 (t, J = 6.7 Hz, 1H), 4.46 (t, J = 6.6 Hz, 1H), 4.16 (t, J =
		6.5 Hz, 1H), 3.68 (t, J = 6.6 Hz, 1H), 3.60 (ddd, J = 20.6, 12.7, 7.7
		Hz, 2H), 3.46 (dd, J = 9.0, 3.7 Hz, 1H), 3.40-3.27 (m, 2H), 2.96
		(d, J = 16.7 Hz, 1H).
304	1.3
		Compound 304: 4-chlorobenzyl (S)-(4-(1-isopropyl-5-
		oxopiperazin-2-yl)phenyl)carbamate. LRMS (ES) m/z: 402.1
		[M + H]+. 1H NMR (400 MHz, Chloroform-d) δ 8.11 (s, 1H), 7.45-
		7.24 (m, 7H), 6.98 (s, 1H), 6.52 (s, 1H), 5.19 (s, 2H), 3.73 (dd,
		J = 10.3, 3.7 Hz, 1H), 3.56 (d, J = 17.2 Hz, 1H), 3.44 (t, J = 11.1
		Hz, 1H), 3.26 (t, J = 14.5 Hz, 2H), 2.93 (p, J = 6.7 Hz, 1H), 1.05
		(d, J = 6.8 Hz, 3H), 0.79 (d, J = 6.4 Hz, 3H).
249	5.1
		Compound 249: N-(4-{[(5R)-2-oxo-5-(pyridin-3-yl)pyrrolidin-
		1-yl]methyl}phenyl)carbamate. LCMS-APCI (POS.) m/z:
		436.1 [M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.50 (d, J =
		4.8 Hz, 1H), 8.33 (s, 1H), 7.69 (dd, J = 8.0, 2.0 Hz, 1H), 7.50-
		7.28 (m, 7H), 7.01-6.88 (m, 2H), 5.16 (s, 2H), 4.80 (d, J = 14.8
		Hz, 1H), 4.61 (t, J = 7.0 Hz, 1H), 3.71 (d, J = 14.8 Hz, 1H), 2.74-
		2.44 (m, 3H), 2.01-1.87 (m, 1H).
63	5.2
		Compound 63: (4-chlorophenyl)methyl N-[4-({3-oxo-2-
		azabicyclo[3.1.0]hexan-2-yl}methyl)phenyl]carbamate.
		LCMS-ESI (POS.) m/z: 371.1 [M + H]+. 1H NMR (400 MHz,
		Methanol-d4) δ 7.37-7.17 (m, 6H), 7.09 (d, J = 8.3 Hz, 2H),
		5.01 (s, 2H), 4.36-4.17 (m, 2H), 2.87 (ddt, J = 7.0, 5.1, 1.8 Hz,
		1H), 2.66 (dd, J = 18.1, 7.4 Hz, 1H), 2.22 (d, J = 18.1 Hz, 1H),
		1.41-1.27 (m, 1H), 0.65 (dt, J = 8.4, 5.5 Hz, 1H), −0.00 (td, J =
		5.4, 2.1 Hz, 1H).
84	5.3
		Compound 84: (4-chlorophenyl)methyl N-[4-({4-oxo-5-
		azaspiro[2.4]heptan-5-yl}methyl)phenyl]carbamate. LCMS-
		ESI (POS.) m/z: 385.1 [M + H]+. 1H NMR (400 MHz, Methanol-
		d4) δ 7.33 (d, J = 8.0 Hz, 2H), 7.30-7.21 (m, 4H), 7.08 (d, J =
		8.1 Hz, 2H), 5.06 (s, 2H), 4.33 (s, 2H), 3.28 (m, 2H), 2.00 (t, J =
		7.4 Hz, 2H), 1.01 (q, J = 4.3, 3.8 Hz, 2H), 0.70 (t, J = 3.5 Hz,
		2H).
123	5.4
		Compound 123: (4-chlorophenyl)methyl N-{4-[(3,3-
		dimethyl-2-oxopyrrolidin-1-yl)methyl]phenyl}carbamate.
		LCMS-ESI (POS.) m/z: 387.1 [M + H]+. 1H NMR (400 MHz,
		Methanol-d4) δ 7.37-7.19 (m, 6H), 7.10-7.01 (m, 2H), 5.06 (s,
		2H), 4.28 (s, 2H), 3.09 (t, J = 6.9 Hz, 2H), 1.76 (t, J = 6.9 Hz,
		2H), 1.06 (d, J = 1.6 Hz, 6H).
180	5.5
		Compound 180: (4-chlorophenyl)methyl N-[4-({2-oxo-3-
		azabicyclo[3.1.0]hexan-3-yl}methyl)phenyl]carbamate. LCMS-ES
		(Pos) m/z:371 [M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.79
		(s, 1H), 7.49-7.38 (m, 6H), 7.06 (d, J = 8.1 Hz, 2H), 5.13 (s,
		2H), 4.15 (s, 2H), 3.32-3.28 (m, 1H), 3.08 (d, J = 10.5 Hz, 1H),
		1.89-1.77 (m, 2H), 1.07-1.01 (m, 1H), 0.46-0.40 (m, 1H).

Method 2: Preparation Isocyanate from Aniline and Triphosgene

Example G

Preparation of 4-chlorobenzyl (S)-(4-(1-methyl-5-oxopiperazin-2-yl)phenyl)carbamate (Compound 54)

To a solution of triphosgene (60 mg, 0.20 mmol) in 2 mL of methylene chloride at 0° C. chilled with ice bath was added dropwise a solution of (S)-5-(4-aminophenyl)-4-methylpiperazin-2-one 2HCl salt (intermediate 1.0, 139 mg, 0.5 mmol) and diisopropylethylamine (0.35 mL, 2.0 mmol) in methylene chloride (4 mL) under nitrogen atmosphere while the internal temperature was kept under 5° C. After 0.5 h of stirring under ice bath, the resultant mixture was slowly added to a solution of 4-chlorobenzyl alcohol (109 mg, 0.75 mmol) and DMAP (6 mg, 0.05 mmol) in methylene chloride (2 mL). The mixture was warmed to room temperature and stirred at rt overnight and was concentrated to dryness. The residue was purified on Agilent RP-HPLC on a Phenomenex, Gemini 5u C18 150×21.2 mm column with a gradient of 10% ACN/Water to 100% ACN/Water over 40 min to give the desired product (115 mg, yield 62%) as an off-white solid. LRMS (ES) m/z: 374 [M+H]⁺. ¹H NMR (400 MHz, Methanol-d₄) δ 7.52-7.29 (m, 9H), 5.18 (s, 2H), 3.54 (d, J=17.1 Hz, 1H), 3.42 (s, 2H), 3.50-3.37 (m, 1H), 3.29 (d, J=8.2 Hz, 1H), 3.05 (d, J=17.0 Hz, 1H), 2.06 (s, 3H).

Compounds in the following table were prepared in a similar manner as Compound 54, using the aniline intermediates and alcohols as listed. Aniline intermediates were either purchased from commercial source or prepared according to the above procedures or to the procedures of published patent application WO 2021/159015.

Co #	Aniline	Alcohol	Structure, Name and Data
263	1.4	(4- methoxyphenyl) methanol
			Compound 263: 4-methoxybenzyl (S)-(4-(1-methyl-5-
			oxopiperazin-2-yl)phenyl)carbamate. LRMS (ES) m/z:
			370.1 [M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.16
			(s, 1H), 7.48 (d, J = 8.2 Hz, 2H), 7.40-7.24 (m, 4H), 6.97-
			6.87 (m, 2H), 5.12 (s, 2H), 3.81 (s, 3H), 3.54 (d, J = 17.1
			Hz, 1H), 3.43 (s, 1H), 3.50-3.37 (m, 1H), 3.29 (d, J = 7.8
			Hz, 1H), 3.06 (d, J = 17.1 Hz, 1H), 2.06 (s, 3H).
81	1.4	(4-chloro-2- fluorophenyl) methanol
			Compound 81: 4-chloro-2-fluorobenzyl (S)-(4-(1-
			methyl-5-oxopiperazin-2-yl)phenyl)carbamate. LRMS
			(ES) m/z: 392.1 [M + H]+. 1H NMR (400 MHz, Methanol-
			d4) δ 7.51 (dd, J = 10.6, 8.0 Hz, 3H), 7.33 (d, J = 8.2 Hz,
			2H), 7.29-7.21 (m, 2H), 5.23 (s, 2H), 3.57 (d, J = 17.0
			Hz, 1H), 3.46 (d, J = 8.2 Hz, 2H), 3.37-3.28 (m, 2H),
			3.10 (d, J = 17.1 Hz, 1H), 2.08 (s, 3H).
278	1.4	(4- fluorophenyl) methanol
			Compound 278: 4-fluorobenzyl (S)-(4-(1-methyl-5-
			oxopiperazin-2-yl)phenyl)carbamate. LRMS (ES) m/z:
			358.1 [M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 7.52-
			7.43 (m, 2H), 7.32 (dd, J = 8.5, 1.8 Hz, 1H), 7.16-
			7.07 (m, 1H), 5.18 (s, 2H), 3.58-3.41 (m, 1H), 3.41 (s,
			1H), 3.29 (d, J = 9.5 Hz, 1H), 3.04 (d, J = 17.2 Hz, 1H),
			2.05 (s, 3H).
204	1.4	(4- (difluoromethyl) phenyl) methanol
			Compound 204: 4-(difluoromethyl)benzyl (S)-(4-(1-
			methyl-5-oxopiperazin-2-yl)phenyl)carbamate. LRMS
			(ES) m/z: 390.1 [M + H]+. 1H NMR (400 MHz, Methanol-
			d4) δ 7.57 (s, 4H), 7.50 (d, J = 8.1 Hz, 2H), 7.37-7.29 (m,
			2H), 6.78 (t, J = 56 Hz, 1H), 5.26 (s, 2H), 4.62 (s, 1H),
			3.54 (d, J = 17.0 Hz, 1H), 3.45 (d, J = 10.2 Hz, 1H), 3.42
			(s, 2H), 3.29 (d, J = 8.8 Hz, 1H), 3.04 (d, J = 17.0 Hz, 1H),
			2.06 (s, 3H).
33	N-(4- amino phenyl)- 1-phenyl methane- sulfonamide	(4- chlorophenyl) methanol
			Compound 33: 4-chlorobenzyl (4-
			((phenylmethyl)sulfonamido)phenyl)carbamate.
			1HNMR (300 MHz, DMSO-d6) δ 9.75 (s, 1H), 7.51-7.31
			(m, 9H), 7.26 (dd, J = 6.8, 2.9 Hz, 2H), 7.11 (d, J = 8.9
			Hz, 2H), 5.14 (s, 2H), 4.38 (s, 2H).
61	N-(4- amino phenyl)-1- phenyl methane- sulfonamide	(4- chlorophenyl) methanol
			Compound 61: 4-methoxybenzyl (4-
			((phenylmethyl)sulfonamido)phenyl)carbamate.
			LRMS (ES) m/z: 427 [M + H]+. 1HNMR (300 MHz,
			DMSO-d6) δ 9.63 (d, J = 12.2 Hz, 2H), 7.47-7.28 (m,
			7H), 7.25 (dd, J = 6.8, 2.9 Hz, 2H), 7.09 (d, J = 8.9 Hz,
			2H), 6.98-6.87 (m, 2H), 5.05 (s, 2H), 4.36 (s, 2H), 3.74
			(s, 3H).
242	3-(4- amino benzyl) oxazolidin- 2-one	(4- chlorophenyl) methanol
			Compound 242: (4-chlorophenyl)methyl N-{4-[(2-oxo-
			1,3-oxazolidin-3-yl)methyl]phenyl}carbamate. LCMS-
			APCI (POS.) m/z: 343.1 [M + H]+. 1H NMR (400 MHz,
			Methanol-d4) δ 7.40-7.25 (m, 6H), 7.17-7.12 (m, 2H),
			5.08 (s, 2H), 4.27 (s, 2H), 4.26-4.20 (m, 2H), 3.42-3.34
			(m, 2H).
281	1-(2- (4-amino phenyl) morpholino) ethan-1-one	(4- chlorophenyl) methanol
			Compound 281: (4-chlorophenyl)methyl N-[4-(4-
			acetylmorpholin-2-yl)phenyl]carbamate. LCMS-APCI
			(POS.) m/z: 389.1 [M + H]+. 1H NMR (400 MHz,
			Methanol-d4) δ 7.54-7.21 (m, 8H), 5.16 (s, 2H), 4.52-
			4.30 (m, 2H), 4.04 (dt, J = 11.3, 3.7 Hz, 1H), 3.90-3.76
			(m, 1H), 3.66 (dtd, J = 28.2, 11.8, 2.8 Hz, 1H), 3.43-3.34
			(m, 0.5H), 3.16 (dd, J = 13.4, 10.7 Hz, 0.5H), 2.88 (td, J =
			12.8, 3.7 Hz, 0.5H), 2.69 (dd, J = 13.3, 10.7 Hz, 0.5H),
			2.14, 2.13 (s, 3H).
151	4-(4- amino phenyl) tetrahydro- 2H- thiopyran 1,1- dioxide	(4- chlorophenyl) methanol
			Compound 151: (4-chlorobenzyl (4-(1,1-
			dioxidotetrahydro-2H-thiopyran-4-
			yl)phenyl)carbamate. LCMS-APCI (POS.) m/z: 394.1
			[M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			7.43 (d, J = 27.0 Hz, 6H), 7.17 (d, J = 8.2 Hz, 2H), 5.14
			(s, 2H), 3.27 (s, 1H), 3.14-3.03 (m, 2H), 2.88 (q, J =
			7.2 Hz, 2H), 2.06 (td, J = 9.4, 8.3, 3.3 Hz, 4H).
262	4- (pyridin-4- ylmethyl) aniline	(4- chlorophenyl) methanol
			Compound 262: 4-methoxybenzyl (4-(pyridin-4-
			ylmethyl)phenyl)carbamate. LCMS-APCI (POS.) m/z:
			349.1 [M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.65 (s,
			1 H), 8.44 (d, J = 6.0 Hz, 2 H), 7.39 (d, J = 8.4 Hz, 2 H),
			7.36 (d, J = 8.6 Hz, 2 H), 7.21 (d, J = 6.0 Hz, 2 H), 7.15
			(d, J = 8.4 Hz, 2 H), 6.94 (d, J = 8.6 Hz, 2 H), 5.05 (s, 2H),
			3.89 (s, 2 H), 3.75 (s, 3 H).
306	4- (pyridin- 4-ylmethyl) aniline	(4- cyanophenyl) methanol
			Compound 306: 4-cyanobenzyl (4-(pyridin-4-
			ylmethyl)phenyl)carbamate. LCMS-APCI (POS.) m/z:
			344.1 ([M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.83
			(s, 1 H), 8.44 (d, J = 6.0 Hz, 2 H), 7.88 (d, J = 8.2 Hz, 2 H),
			7.61 (d, J = 8.0 Hz, 2 H), 7.40 (d, J = 8.1 Hz, 2 H), 7.21
			(d, J = 5.9 Hz, 2 H), 7.17 (d, J = 8.5 Hz, 2 H), 5.23 (s, 2
			H), 3.90 (s, 2 H).
86	4-(4- amino benzyl) morpholin- 3-one	(4- chlorophenyl) methanol
			Compound 86: (4-chlorophenyl)methyl N-{4-[(3-
			oxomorpholin-4-yl)methyl]phenyl}carbamate. LCMS-
			ESI (POS.) m/z: 375.0 [M + H]+. 1H NMR (400 MHz,
			DMSO-d6) δ 9.81 (s, 1H), 7.45 (d, J = 13.7 Hz, 6H), 7.27-
			7.07 (m, 2H), 5.14 (s, 2H), 4.47 (s, 2H), 4.10 (s, 2H),
			3.79 (dd, J = 5.9, 4.3 Hz, 2H), 3.22 (dd, J = 6.0, 4.3 Hz,
			2H).
174	4-(4- amino benzyl) morpholin- 3-one	(4- methoxyphenyl) methanol
			Compound 174: (4-methoxyphenyl)methyl N-{4-[(3-
			oxomorpholin-4-yl)methyl]phenyl}carbamate. LCMS-
			ESI (POS.) m/z: 371.0 [M + H]+. 1H NMR (300 MHz,
			DMSO-d6) δ 9.71 (s, 1H), 7.48-7.28 (m, 4H), 7.23-7.08
			(m, 2H), 7.06-6.80 (m, 2H), 5.07 (s, 2H), 4.47 (s, 2H),
			4.10 (s, 2H), 3.87-3.64 (m, 5H), 3.22 (dd, J = 6.0, 4.3
			Hz, 2H).
247	3.1	(4- chlorophenyl) methanol
			Compound 247: 4-chlorobenzyl (4-(1-hydroxy-1-
			(pyridin-4-yl)ethyl)phenyl)carbamate. LRMS (ES)
			m/z: 383 [M + H]+. 1H NMR (400 MHz, Methanol-d4) δ
			8.46 (d, J = 5.3 Hz, 2H), 7.53 (d, J = 5.2 Hz, 2H), 7.45-
			7.35 (m, 8H), 5.16 (s, 2H), 1.91 (s, 3H).
296	3.1	oxazol-5- ylmethanol
			Compound 296: oxazol-5-ylmethyl (4-(1-hydroxy-1-
			(pyridin-4-yl)ethyl)phenyl)carbamate. LRMS (ES)
			m/z: 340 [M + H]+. 1H NMR (400 MHz, Methanol-d4) δ
			8.46 (d, J = 5.3 Hz, 2H), 8.23 (s, 1H), 7.53 (d, J = 5.0
			Hz, 2H), 7.46-7.32 (m, 4H), 7.25 (s, 1H), 5.24 (s, 2H),
			1.92 (s, 3H).
329	3.1	thiazol-5- ylmethanol
			Compound 329: thiazol-5-ylmethyl (4-(1-hydroxy-1-
			(pyridin-4-yl)ethyl)phenyl)carbamate. LRMS (ES)
			m/z: 356 [M + H]+. 1H NMR (400 MHz, Methanol-d4) δ
			9.02 (s, 1H), 8.46 (d, J = 5.2 Hz, 2H), 7.96 (s, 1H), 7.53
			(d, J = 5.2 Hz, 2H), 7.46-7.329 (m, 4H), 5.43 (s, 2H),
			1.92 (s, 3H).
	tert-butyl 4-(4- amino benzyl) piperidine- 1-carboxylate	(4- chlorophenyl) methanol
			Intermediate 6.1: tert-butyl 4-(4-((((4-
			chlorobenzyl)oxy)carbonyl)amino)benzyl)piperidine-
			1-carboxylate. LRMS (ES) m/z: 403[M + H-tBu]+. 1H
			NMR (400 MHz, Methanol-d4) δ 7.58-7.23 (m, 6H), 7.23-
			6.88 (m, 2H), 5.16 (s, 2H), 4.04 (d, J = 13.4 Hz, 2H),
			2.69 (t, J = 12.8 Hz, 2H), 2.59-2.34 (m, 2H), 1.66 (dd, J =
			33.1, 11.7 Hz, 3H), 1.46 (d, J = 3.3 Hz, 9H), 1.09 (q, J =
			12.4 Hz, 2H).
67	4-((1- (oxetan-3- yl)piperidin- 4-yl)methyl) aniline	(4- methoxyphenyl) methanol
			Compound 67: 4-methoxybenzyl (4-((1-(oxetan-3-
			yl)piperidin-4-yl)methyl)phenyl)carbamate. LCMS-
			ESI (POS.) m/z: 411.0 [M + H]+. 1H NMR (300 MHz,
			DMSO-d6) δ 9.60 (d, J = 4.6 Hz, 1H), 7.35 (s, 4H), 7.05
			(s, 2H), 6.94 (s, 2H), 5.06 (s, 2H), 4.49 (d, J = 6.6 Hz, 2H),
			4.38 (s, 2H), 3.75 (t, J = 4.1 Hz, 3H), 2.61 (d, J = 8.2 Hz,
			2H), 2.42 (s, 3H), 1.64 (s, 2H), 1.52 (d, J = 12.6 Hz, 3H),
			1.16 (s, 2H).
	tert- butyl 4-(4- amino phenyl) piperidine-1- carboxylate	(4- chlorophenyl) methanol
			Intermediate 7.1: tert-butyl 4-[4-({[(4-
			chlorophenyl)methoxy]carbonyl}amino)phenyl]piperidine-
			1-carboxylate. LCMS-APCI (POS.) m/z: 445.1
			[M + H]+.
	tert-butyl 4-(4- amino benzyl) piperidine-1- carboxylate	oxazol-5- ylmethanol
			Intermediate 8.1: tert-butyl 4-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)piperidine-1-
			carboxylate. LRMS (ES) m/z: 360 [M + H-tBu]+. 1H NMR
			(400 MHz, Methanol-d4) δ 8.24 (s, 1H), 7.35 (d, J = 8.0
			Hz, 2H), 7.25 (s, 1H), 7.10 (d, J = 8.1 Hz, 2H), 5.25 (s,
			2H), 4.05 (d, J = 13.2 Hz, 2H), 2.70 (s, 2H), 2.51 (d, J =
			7.0 Hz, 2H), 1.63 (d, J = 13.8 Hz, 3H), 1.46 (d, J = 1.4 Hz,
			9H), 1.10 (qd, J = 12.5, 4.3 Hz, 2H).
	tert- butyl 4-(4- amino phenyl) piperidine-1- carboxylate	oxazol-5- ylmethanol
			Intermediate 9.1: tert-butyl 4-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)phenyl)piperidine-1-
			carboxylate. LRMS (ES) m/z: 402.1 M + H]+.
	tert- butyl 4-(4- amino benzyl) piperidine-1- carboxylate	pyridin-4- ylmethanol
			Intermediate 10.1: tert-butyl 4-(4-(((pyridin-4-
			ylmethoxy)carbonyl)amino)benzyl)piperidine-1-
			carboxylate. LCMS-APCI (POS.) m/z: 426.0 [M + H]+.
121	2.1	oxazol-5- ylmethanol
			Compound 121: tert-butyl 4-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)phenethyl)piperidine-1-
			carboxylate. LRMS (ES) m/z: 430 [M + H]+. 1H NMR
			(400 MHz, Methanol-d4) δ 8.24 (s, 1H), 7.34 (d, J = 8.1
			Hz, 2H), 7.25 (s, 1H), 7.12 (d, J = 8.5 Hz, 2H), 5.24 (s,
			2H), 4.06 (dt, J = 13.2, 2.8 Hz, 2H), 2.72 (m, 2H), 2.62
			(dd, J = 9.0, 6.7 Hz, 2H), 1.86-1.69 (m, 2H), 1.66-1.45
			(m, 3H), 1.47 (s, 9H), 1.10 (qd, J = 12.6, 4.3 Hz, 2H).
	4- bromo aniline	(4- chlorophenyl) methanol
			Intermediate 12.1: 4-chlorobenzyl (4-
			bromophenyl)carbamate. LRMS (ES) m/z: 341[M + H]+.
	4.1	(4- chlorophenyl) methanol
			Intermediate 13.1: tert-butyl 4-{[4-({[(4-
			chlorophenyl)methoxy|carbonyl}amino)phenyl]methoxy}
			piperidine-1-carboxylate.
			LCMS-APCI (POS.) m/z: 375.1 [M + H-Boc]+.
			1H NMR (400 MHz, Methanol-d4) δ 7.45-7.34 (m, 6H),
			7.26 (d, J = 8.2 Hz, 2H), 5.15 (s, 2H), 4.50 (s, 2H), 3.73
			(dt, J = 11.0, 4.5 Hz, 2H), 3.60 (tt, J = 8.0, 3.5 Hz, 1H),
			3.11 (m, 2H), 1.90-1.81 (m, 2H), 1.51 (m, 2H), 1.45 (s,
			9H).
288	4.2	(4- chlorophenyl) methanol
			Compound 288: tert-butyl 3-{[4-({[(4-
			chlorophenyl)methoxy]carbonyl}amino)phenyl]methoxy}
			azetidine-1-carboxylate. LCMS-APCI (POS.) m/z:
			347.1 [M + H-Boc]+.
			1H NMR (400 MHz, Methanol-d4) δ 7.48-7.23 (m, 8H),
			5.16 (s, 2H), 4.42 (s, 2H), 4.34 (s, 2H), 4.09-3.97 (m,
			2H), 3.79-3.68 (m, 2H), 1.42 (s, 9H).
291	4.3	(4- methoxyphenyl) methanol
			Compound 291: 4-methoxybenzyl (4-(((1-(oxetan-3-
			yl)piperidin-4-yl)oxy)methyl)phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 427.2 [M + H]+.
			1H NMR (400 MHz, Methanol-d4) δ 7.40 (d, J = 8.2 Hz,
			2H), 7.36-7.32 (m, 2H), 7.25 (d, J = 8.4 Hz, 2H), 6.94-
			6.89 (m, 2H), 5.10 (s, 2H), 4.67 (t, J = 6.7 Hz, 2H), 4.58
			(t, J = 6.3 Hz, 2H), 4.48 (s, 2H), 3.79 (s, 3H), 3.51 (p, J =
			6.4 Hz, 2H), 2.66-2.57 (m, 2H), 2.11 (t, J = 9.9 Hz,
			2H), 1.98-1.88 (m, 2H), 1.73-1.60 (m, 2H).
217	4.4	(4- methoxyphenyl) methanol
			Compound 217: 4-methoxybenzyl (4-(((1-
			acetylpiperidin-4-yl)oxy)methyl)phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 413.1 [M + H]+. 1H NMR (400
			MHz, Methanol-d4) δ 7.41 (d, J = 8.2 Hz, 2H), 7.34 (d, J =
			8.3 Hz, 2H), 7.26 (d, J = 8.2 Hz, 2H), 6.91 (d, J = 8.0
			Hz, 2H), 5.09 (s, 2H), 4.50 (s, 2H), 3.92-3.83 (m, 1H),
			3.78 (s, 3H), 3.76-3.62 (m, 2H), 3.31-3.23 (m, 2H),
			2.08 (s, 3H), 1.94-1.79 (m, 2H), 1.65-1.48 (m, 2H).
	tert- butyl (4- amino benzyl) carbamate	4- chlorobenzyl alcohol
			Intermediate 15.1: (4-chlorophenyl)methyl N-(4-
			{[(tert-
			butoxycarbonyl)amino]methyl}phenyl)carbamate.
			LCMS-ESI (NEG.) m/z: 389.0 [M − H]−.
	tert- butyl (S)-(1-(4- amino phenyl) ethyl) carbamate	4- chlorobenzyl alcohol
			Intermediate 16.1: (4-chlorophenyl)methyl N-(4-[(1S)-
			1-[(tert-
			butoxycarbonyl)amino]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 405.1 [M + H]+.
	tert- butyl (4-amino benzyl) (methyl) carbamate	4- chlorobenzyl alcohol
			Intermediate 17.1: (4-chlorophenyl)methyl N-(4-
			{[(tert-
			butoxycarbonyl)(methyl)amino methyl}phenyl)carbamate.
			LCMS-ES (POS.) m/z: 427.0 [M + Na]+.
	tert- butyl (4- amino benzyl) (methyl) carbamate	4- chlorobenzyl alcohol
			Intermediate 18.1: tert-butyl (S)-(1-(4-((((4-
			chlorobenzyl)oxy)carbonyl)amino)phenyl)ethyl)(methyl)
			carbamate. LCMS-ES (POS.) m/z: 419.0 [M + H]+.
	tert- butyl (4-amino benzyl) carbamate	1,3-oxazol- 5- ylmethanol
			Intermediate 19.1: 1,3-oxazol-5-ylmethyl N-(4-{[(tert-
			butoxycarbonyl)amino methyl}phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 348.1 [M + H]+.
	tert- butyl (S)-(1- (4-amino phenyl) ethyl) carbamate	1,3-oxazol- 5- ylmethanol
			Intermediate 20.1: 1,3-oxazol-5-ylmethyl N-{4-[(1S)-1-
			[(tert-
			butoxycarbonyl)amino]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 362.2 [M + H]+.
322	4-[(5- methyl- 1,3,4- oxadiazol-2- yl)methyl] aniline	4- chlorobenzyl alcohol
			Compound 322: (4-chlorophenyl)methyl N-{4-[(5-
			methyl-1,3,4-oxadiazol-2-
			yl)methyl]phenyl}carbamate. LCMS-APCI (POS.) m/z:
			358.3 [M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.80 (s,
			1H), 7.49-7.44 (m, 4H), 7.42 (d, J = 7.9 Hz, 2H), 7.21
			(d, J = 8.1 Hz, 2H), 5.13 (s, 2H), 4.13 (s, 2H), 2.43 (s, 3H).
	ethyl 2-(4- amino phenyl) acetate	(4- chlorophenyl) methanol
			Intermediate 21.1: ethyl 2-(4-((((4-
			chlorobenzyl)oxy)carbonyl)amino)phenyl)acetate.
			LRMS (ES) m/z: 348.1 [M + H]+.
	4- amino benzenesulfonyl chloride	(4- chlorophenyl) methanol
			Intermediate 22.1: (4-chlorophenyl)methyl N-[4-
			(chlorosulfonyl)phenyl]carbamate. 1H NMR (400
			MHz, DMSO-d6) δ 9.87 (s, 1H), 7.50 (d, J = 8.6 Hz, 2H),
			7.40-7.30 (m, 6H), 5.14 (s, 2H).
	27.2	1,3-oxazol- 5-ylmethanol
			Intermediate 29.1: tert-butyl 6-(4-((2-(oxazol-5-
			ylmethoxy)-2-oxoethyl)amino)phenyl)-2-
			azaspiro[3.3]heptane-2-carboxylate
			LCMS-ESI (POS.) m/z: 358.1 [M + H-Bu]+
	27.3	1,3-oxazol- 5-ylmethanol
			Intermediate 29.2: tert-butyl 2-(2-fluoro-4-(((oxazol-
			5-ylmethoxy)carbonyl)amino)phenyl)-6-
			azaspiro[3.4]octane-6-carboxylate
			LCMS-ESI (POS.) m/z: 390.1 [M + H-Bu]+
	tert- butyl (R)-3-(4- amino phenyl) piperidine-1- carboxylate	1,3-oxazol- 5-ylmethanol
			Intermediate 29.3: tert-butyl (R)-3-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)phenyl)piperidine-1-
			carboxylate
			LCMS-ESI (POS.) m/z: 346.1 [M + H-Bu]+
	28.2	1,3-oxazol- 5-ylmethanol
			Intermediate 29.4: tert-butyl 2-(2-fluoro-4-(((oxazol-
			5-ylmethoxy)carbonyl)amino)benzyl)-6-
			azaspiro[3.4]octane-6-carboxylate
			LCMS-ESI (POS.) m/z: 460.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.94 (s, 1H), 8.42 (s,
			1H), 7.36-7.23 (m, 2H), 7.22-7.05 (m, 2H), 5.22 (s,
			2H), 3.23-3.12 (m, 3H), 3.09 (s, 1H), 2.68-2.57 (m,
			2H), 2.05-1.83 (m, 2H), 1.84-1.75 (m, 1H), 1.74-
			1.62 (m, 4H), 1.37 (s, 9H).
	tert- butyl (S)-3-(4- amino phenyl) piperidine-1- carboxylate	1,3-oxazol- 5-ylmethanol
			Intermediate 29.5: tert-butyl (S)-3-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)phenyl)piperidine-1-
			carboxylate
			LCMS-ESI (POS.) m/z: 346.1 [M + H-Bu]+
	28.1	1,3-oxazol- 5-ylmethanol
			Intermediate 29.6: tert-butyl 6-(2-fluoro-4-(((oxazol-
			5-ylmethoxy)carbonyl)amino)benzyl)-2-
			azaspiro[3.3]heptane-2-carboxylate
			LCMS-ESI (POS.) m/z: 446.1 [M + H]+
	27.1	1,3-oxazol- 5-ylmethanol
			Intermediate 29.7: tert-butyl 6-(2-fluoro-4-(((oxazol-
			5-ylmethoxy)carbonyl)amino)phenyl)-2-
			azaspiro[3.3]heptane-2-carboxylate
			LCMS-ESI (POS.) m/z: 376.1 [M + H-Bu]+
	28.8	1,3-oxazol- 5-ylmethanol
			Intermediate 29.8: tert-butyl 3-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)-8-
			azabicyclo[3.2.1]octane-8-carboxylate
			LCMS-ESI (POS.) m/z: 386.1 [M + H-Bu]+
	tert- butyl 4-(4- amino- 2-fluoro phenyl) piperidine-1- carboxylate	1,3-oxazol- 5- ylmethanol
			Intermediate 29.9: tert-butyl 4-(2-fluoro-4-(((oxazol-
			5-ylmethoxy)carbonyl)amino)phenyl)piperidine-1-
			carboxylate
			LCMS-ESI (POS.) m/z: 420.1 [M + H]+
	28.5	1,3-oxazol- 5-ylmethanol
			Intermediate 29.10: tert-butyl 7-[(4-{[(1,3-oxazol-5-
			ylmethoxy)carbonyl]amino}phenyl)methyl]-4-
			azaspiro[2.5]octane-4-carboxylate
			LCMS-ESI (POS.) m/z: 420.1 [M + H]+
	28.3	1,3-oxazol- 5-ylmethanol
			Intermediate 29.11: tert-butyl 8-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)-3-
			azabicyclo[3.2.1]octane-3-carboxylate
			LCMS-ESI (POS.) m/z: 442.2 [M + H]+
	28.4	1,3-oxazol- 5-ylmethanol
			Intermediate 29.12: tert-butyl 6-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)-3-
			azabicyclo[3.1.1]heptane-3-carboxylate
			LCMS-ESI (POS.) m/z: 428.2 [M + H]+
	28.7	1,3-oxazol- 5- ylmethanol
			Intermediate 29.15: tert-butyl 4-(2-fluoro-4-(((oxazol-
			5-ylmethoxy)carbonyl)amino)benzyl)piperidine-1-
			carboxylate.
			LCMS-ESI (POS.) m/z: 378.1 [M + H-Boc]+
	28.6	1,3-oxazol- 5-ylmethanol
			Intermediate 29.16: tert-butyl 5-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)-2-
			azabicyclo[4.1.0]heptane-2-carboxylate
			LCMS-ESI (POS.) m/z: 372.1 [M + H-Bu]+
377	28.2	1,3-oxazol- 5-ylmethanol
			Compound 377: tert-butyl 2-(2-fluoro-4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)-6-
			azaspiro[3.4]octane-6-carboxylate
			LCMS-ES (POS.) m/z: 460.2 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.94 (s, 1H), 8.42 (s,
			1H), 7.36-7.23 (m, 2H), 7.22-7.05 (m, 2H), 5.22 (s,
			2H), 3.23-3.12 (m, 3H), 3.09 (s, 1H), 2.68-2.57 (m,
			2H), 2.05-1.83 (m, 2H), 1.84-1.75 (m, 1H), 1.74-
			1.62 (m, 4H), 1.37 (s, 9H).
	tert- butyl 4-(4- amino benzyl) piperidine-1- carboxylate	thiazol-5- ylmethanol
			Intermediate 29.17: tert-butyl 4-(4-(((thiazol-5-
			ylmethoxy)carbonyl)amino)benzyl)piperidine-1-
			carboxylate
			LCMS-ESI (POS.) m/z: 376.1 [M + H-Bu]+

Method 3: In Situ Preparation Isocyanate Via Curtius Rearrangement

Example H

Preparation of oxazol-5-ylmethyl (4-(pyridin-4-ylmethyl)phenyl)carbamate (Compound 201)

Step 1A: Synthesis of methyl 4-(pyridin-4-ylmethyl)benzoate

To a solution of 4-(chloromethyl)pyridine hydrochloride (4.92 g, 30 mmol, 1.00 equiv) and 4-(methoxycarbonyl)phenylboronic acid (7.02 g, 39 mmol, 1.30 equiv) in dioxane (70 mL) and H₂O (30 mL) was added cesium carbonate (14.66 g, 45 mmol, 1.50 equiv) and PdCl₂(dppf) (2.20 g, 3 mmol, 0.10 equiv). The reaction mixture was heated at 110° C. in the oil bath for 3 h. The mixture was cooled down to rt and then extracted with EtOAc (100 mL) and H₂O (50 mL). The organic layer was dried, concentrated and purified on silica gel with 50% EtOAc/Hex to afford the desired product methyl 4-(pyridin-4-ylmethyl)benzoate as a white solid (1.70 g, 25%). LRMS (ES) m/z: 228[M+H]⁺.

Step 1B: Synthesis of methyl 4-((6-methylpyridin-3-yl)methyl)benzoate

To a solution of 5-(chloromethyl)-2-methylpyridine (3.00 g, 21 mmol, 1.00 equiv) and (4-(methoxycarbonyl)phenyl)boronic acid (5.67 g, 31.50 mmol, 1.50 equiv) in dioxane (80 mL) and H₂O (40 mL) was added cesium carbonate (13.68 g, 42 mmol, 2.00 equiv) and PdCl₂(dppf) (1.54 g, 2.10 mmol, 0.10 equiv). The reaction mixture was heated at 110° C. in the oil bath for 3 h. The mixture was cooled down to rt and then extracted with EtOAc (100 mL) and H₂O (50 mL). The organic layer was dried, concentrated and purified on silica gel with 50% EtOAc/Hex to afford the desired product methyl 4-((6-methylpyridin-3-yl)methyl)benzoate as a white solid (3.87 g, 76%). LRMS (ES) m/z: 242[M+H]⁺. ¹H NMR (400 MHz, Methanol-d₄) δ 8.30 (s, 1H), 7.92 (d, J=7.9 Hz, 2H), 7.54 (d, J=7.8 Hz, 1H), 7.30 (d, J=7.9 Hz, 2H), 7.20 (d, J=8.0 Hz, 1H), 4.00 (s, 2H), 3.86 (s, 3H), 2.48 (s, 3H).

Step 1C: Synthesis of ethyl 4-((6-methylnicotinamido)methyl)benzoate

To a solution of 6-methylnicotinic acid (3.43 g, 25 mmol, 1.00 equiv) in DMF (100 mL) was added HBTU (12.32 g, 32.50 mmol, 1.30 equiv), DIEA (6.77 g, 52.50 mmol, 2.10 equiv). The mixture was stirred for 10 min. ethyl 4-(aminomethyl)benzoate (5.38 g, 30 mmol, 1.20 equiv) was added. The reaction mixture was stirred for 1 h. Then the reaction mixture was added EtOAc (120 mL) and brine (150 mL). The organic layer was further washed with s. NaHCO₃(150 mL), dried over MgSO₄, concentrated and purified on silica gel with 100% EtOAc to afford the desired product ethyl 4-((6-methylnicotinamido)methyl)benzoate as a brownish solid (2.98 g, 40%). LRMS (ES) m/z: 299 [M+H]⁺. ¹H NMR (400 MHz, Methanol-d₄) δ 8.91 (d, J=2.6 Hz, 1H), 8.18 (dd, J=8.2, 2.3 Hz, 1H), 8.00 (dd, J=8.3, 2.3 Hz, 2H), 7.53-7.23 (m, 3H), 4.66 (d, J=2.2 Hz, 2H), 4.36 (dd, J=7.2, 2.2 Hz, 2H), 2.61 (d, J=2.1 Hz, 3H), 1.39 (t, J=7.1 Hz, 3H).

Step 2: Synthesis of 4-(pyridin-4-ylmethyl)benzoic acid

To a solution of methyl 4-(pyridin-4-ylmethyl)benzoate (1.70 g, 7.50 mmol, 1.00 equiv) in MeOH (10 mL) and THF (10 mL) was added NaOH (10 mL, 1.50 M, 2.00 equiv). The reaction mixture was stirred at rt for 16 h. THF and MeOH were removed. The residue was adjusted PH=3-4 by using 2N HCl (7.50 mL). The precipitate was filtered and washed with H₂O, dried over high vacuum to afford the desired product 4-(pyridin-4-ylmethyl)benzoic acid (1.35 g, 84%) as a white solid. LRMS (ES) m/z: 214 [M+H]⁺.

Step 3: Synthesis of 4-(pyridin-4-ylmethyl)benzoyl azide

To a mixture of 4-(pyridin-4-ylmethyl)benzoic acid (1.75 g, 8.21 mmol, 1.00 equiv) in toluene/THF (20 mL/20 mL) was added Et₃N (0.83 g, 8.21 mmol, 1.00 equiv), followed by diphenylphosphoryl azide (2.26 g, 8.21 mmol, 1.00 equiv) The reaction mixture was stirred at r.t. for 16 h. The reaction mixture was concentrated and purified by silica gel chromatography (0-100% ethyl acetate/hexanes) to afford 4-(pyridin-4-ylmethyl)benzoyl azide as a white solid (1.72 g, 88%). LRMS (ES) m/z: 239 [M+H]⁺.

Step 4: Synthesis of thiazol-5-ylmethyl (4-(pyridin-4-ylmethyl)phenyl)carbamate

To a mixture of 4-(pyridin-4-ylmethyl)benzoyl azide (29 mg, 0.12 mmol, 1.0 equiv) in toluene (1 mL) was added 1,3-thiazol-5-ylmethanol (28 mg, 0.24 mmol, 2.00 equiv). The reaction mixture was heated at 110° C. for 1 h. The solvent was removed and the residue was purified by Prep-HPLC with the following conditions (Column: XBridge Prep OBD C18 Column 30×150 mm 5 um; Mobile Phase A:Water (0.1% formic acid), Mobile Phase B: MeCN (0.1% formic acid; Flow rate: 20 mL/min) to afford the desired product thiazol-5-ylmethyl (4-(pyridin-4-ylmethyl)phenyl)carbamate as a white solid (35 mg, 90%). LRMS (ES) m/z: 326 [M+H]⁺. ¹H NMR (400 MHz, Methanol-d₄) δ 9.02 (s, 1H), 8.42 (d, J=5.2 Hz, 2H), 7.96 (s, 1H), 7.41 (d, J=8.1 Hz, 2H), 7.29 (d, J=5.3 Hz, 2H), 7.17 (d, J=8.1 Hz, 2H), 5.43 (s, 2H), 4.00 (s, 2H).

Compounds in the following table were prepared in a similar manner as compound 201, using the starting materials and alcohols as listed.

Co	Starting
#	Material	Alcohol	Structure, Name and Data
153	4- (chloromethyl) pyridine	oxazol-5- ylmethanol
			Compound 153: oxazol-5-ylmethyl (4-(pyridin-4-
			ylmethyl)phenyl)carbamate. LRMS (ES) m/z: 310
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.42 (s,
			2H), 8.23 (s, 1H), 7.40 (d, J = 8.1 Hz, 2H), 7.34-7.21
			(m, 3H), 7.16 (d, J = 8.1 Hz, 2H), 5.24 (s, 2H), 3.99 (s,
			2H).
355	4- (chloromethyl) pyridine	(1-methyl- 1H-pyrazol- 4- yl)methanol
			Compound 355: (1-methyl-1H-pyrazol-4-yl)methyl (4-
			(pyridin-4-ylmethyl)phenyl)carbamate. LRMS (ES)
			m/z: 323 [M + H]+. 1H NMR (400 MHz, Methanol-d4) δ
			8.41 (d, J = 5.1 Hz, 2H), 7.67 (s, 1H), 7.54 (s, 1H), 7.39
			(d, J = 8.1 Hz, 2H), 7.27 (d, J = 5.1 Hz, 2H), 7.14 (d, J =
			8.1 Hz, 2H), 5.06 (s, 2H), 3.97 (s, 2H), 3.87 (s, 3H).
333	4- (chloromethyl) pyridine	isoxazol-4- ylmethanol
			Compound 333: isoxazol-4-ylmethyl (4-(pyridin-4-
			ylmethyl)phenyl)carbamate. LRMS (ES) m/z: 310
			[M + H]+.
			1H NMR (400 MHz, Methanol-d4) δ 8.79 (s, 1H), 8.53 (s,
			1H), 8.41 (d, J = 5.1 Hz, 2H), 7.40 (d, J = 8.1 Hz, 2H),
			7.28 (d, J = 5.1 Hz, 2H), 7.17 (d, J = 8.1 Hz, 2H), 5.12 (s,
			2H), 3.99 (s, 2H).
219	4- (chloromethyl) pyridine	isothiazol-5- ylmethanol
			Compound 219: isothiazol-5-ylmethyl (4-(pyridin-4-
			ylmethyl)phenyl)carbamate LRMS (ES) m/z: 326
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.48-
			8.32 (m, 3H), 7.43 (d, J = 8.1 Hz, 2H), 7.36 (s, 1H), 7.27
			(d, J = 5.1 Hz, 2H), 7.17 (d, J = 8.2 Hz, 2H), 5.50 (s,
			2H), 3.99 (s, 2H).
299	4- (chloromethyl) pyridine	isothiazol-4- ylmethanol
			Compound 299: isothiazol-4-ylmethyl (4-(pyridin-4-
			ylmethyl)phenyl)carbamate. LRMS (ES) m/z: 326
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.89 (s,
			1H), 8.59 (s, 1H), 8.52-8.25 (m, 2H), 7.41 (d, J = 8.1
			Hz, 2H), 7.25 (d, J = 5.1 Hz, 2H), 7.15 (d, J = 8.2 Hz,
			2H), 5.29 (s, 2H), 3.97 (s, 2H).
169	4- (chloromethyl) pyridine	pyridin-4- ylmethanol
			Compound 169: pyridin-4-ylmethyl (4-(pyridin-4-
			ylmethyl)phenyl)carbamate. LRMS (ES) m/z: 320
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.54 (d, J =
			5.0 Hz, 2H), 8.42 (d, J = 5.1 Hz, 2H), 7.52-7.38(m,
			4H), 7.29 (d, J = 5.0 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H),
			5.27 (s, 2H), 4.00 (s, 2H).
349	4- (chloromethyl) pyridine	pyrimidin- 4- ylmethanol
			Compound 349: pyrimidin-4-ylmethyl (4-(pyridin-4-
			ylmethyl)phenyl)carbamate. LRMS (ES) m/z: 321
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 9.13 (s,
			1H), 8.79 (d, J = 5.2 Hz, 1H), 8.42 (d, J = 5.2 Hz, 2H),
			7.59 (d, J = 5.2 Hz, 1H), 7.44 (d, J = 8.1 Hz, 2H), 7.29 (d,
			J = 5.1 Hz, 2H), 7.18 (d, J = 8.1 Hz, 2H), 5.28 (s, 2H), 4.00
			(s, 2H).
326	4- (chloromethyl) pyridine	pyridazin-4- ylmethanol
			Compound 326: pyridazin-4-ylmethyl (4-(pyridin-4-
			ylmethyl)phenyl)carbamate. LRMS (ES) m/z: 321
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 9.28 (s, 1H),
			9.20 (d, J = 5.3 Hz, 1H), 8.42 (d, J = 5.1 Hz, 2H), 7.84-
			7.71 (m, 1H), 7.43 (d, J = 8.1 Hz, 2H), 7.29 (d, J = 5.1 Hz,
			2H), 7.19 (d, J = 8.1 Hz, 2H), 5.32 (s, 2H), 4.00 (s, 2H).
106	4- (chloromethyl) pyridine	1,4- phenylenedi- methanol
			Compound 106: 4-(hydroxymethyl)benzyl (4-
			(pyridin-4-ylmethyl)phenyl)carbamate. LRMS (ES)
			m/z: 349 [M + H]+. 1H NMR (400 MHz, Methanol-d4) δ
			8.40 (d, J = 5.0 Hz, 2H), 7.47-7.31 (m, 6H), 7.27 (d, J =
			5.0 Hz, 2H), 7.14 (d, J = 8.2 Hz, 2H), 5.17 (s, 2H), 4.61
			(s, 2H), 3.96 (s, 2H).
196	4- (chloromethyl) pyridine	(4- (difluoromethyl) phenyl) methanol
			Compound 196: 4-(difluoromethyl)benzyl (4-(pyridin-
			4-ylmethyl)phenyl)carbamate. LRMS (ES) m/z: 369
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.47-8.24
			(m, 2H), 7.68-7.45 (m, 4H), 7.42 (d, J = 8.2 Hz, 2H),
			7.35-7.25 (m, 2H), 7.25-7.09 (m, 2H), 6.76 (t, J = 56
			Hz, 1H), 5.23 (s, 2H), 3.98 (s, 2H).
14	4- (chloromethyl) pyridine	4- (hydroxymethyl) benzamide
			Compound 14: 4-carbamoylbenzyl (4-(pyridin-4-
			ylmethyl)phenyl)carbamate. LRMS (ES) m/z: 362
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.42 (d, J =
			5.1 Hz, 2H), 7.90 (d, J = 8.1 Hz, 2H), 7.53 (d, J = 8.1 Hz,
			2H), 7.42 (d, J = 8.1 Hz, 2H), 7.30 (d, J = 5.2 Hz, 2H),
			7.17 (d, J = 8.3 Hz, 2H), 5.25 (s, 2H), 4.00 (s, 2H).
99	4- (chloromethyl) pyridine	(1H- pyrazol-4- yl)methanol
			Compound 99: (1H-pyrazol-4-yl)methyl (4-(pyridin-4-
			ylmethyl)phenyl)carbamate LRMS (ES) m/z: 309
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.51-
			8.29 (m, 2H), 7.70 (s, 2H), 7.40 (d, J = 8.1 Hz, 2H), 7.34-
			7.23 (m, 2H), 7.16 (d, J = 8.3 Hz, 2H), 5.12 (s, 2H),
			3.99 (s, 2H).
51	5- (chloromethyl)- 2-methylpyridine	oxazol-5- ylmethanol
			Compound 51: oxazol-5-ylmethyl (4-((6-
			methylpyridin-3-yl)methyl)phenyl)carbamate. LRMS
			(ES) m/z: 324 [M + H]+. 1H NMR (400 MHz, Methanol-
			d4) δ 8.29 (s, 1H), 8.23 (s, 1H), 7.60 (dd, J = 8.1, 2.0 Hz,
			1H), 7.38 (d, J = 8.1 Hz, 2H), 7.26 (d, J = 11.2 Hz, 2H),
			7.14 (d, J = 8.1 Hz, 2H), 5.23 (s, 2H), 3.93 (s, 2H), 2.51
			(s, 3H).
114	5- (chloromethyl)- 2-methylpyridine	thiazol-5- ylmethanol
			Compound 114: thiazol-5-ylmethyl (4-((6-
			methylpyridin-3-yl)methyl)phenyl)carbamate. LRMS
			(ES) m/z: 340 [M + H] 1H NMR (400 MHz, Methanol-d4)
			δ 9.01 (s, 1H), 8.29 (s, 1H), 7.95 (s, 1H), 7.61 (d, J = 8.1
			Hz, 1H), 7.39 (d, J = 8.1 Hz, 2H), 7.26 (d, J = 8.0 Hz,
			1H), 7.14 (d, J = 8.1 Hz, 2H), 5.41 (s, 2H), 3.93 (s, 2H),
			2.51 (s, 3H).
186	5- (chloromethyl)- 2-methylpyridine	pyridin-4- ylmethanol
			Compound 186: pyridin-4-ylmethyl (4-((6-
			methylpyridin-3-yl)methyl)phenyl)carbamate. LRMS
			(ES) m/z: 334 [M + H]+. 1H NMR (400 MHz, Methanol-
			d4) δ 8.53 (d, J = 5.0 Hz, 2H), 8.30 (s, 1H), 7.62 (dd, J =
			8.1, 2.0 Hz, 1H), 7.47 (d, J = 5.1 Hz, 2H), 7.42 (d, J = 8.2
			Hz, 2H), 7.27 (d, J = 8.0 Hz, 1H), 7.15 (d, J = 8.1 Hz,
			2H), 5.26 (s, 2H), 3.94 (s, 2H), 2.52 (s, 3H).
331	5- (chloromethyl)- 2-methylpyridine	(4- fluorophenyl) methanol
			Compound 331: 4-fluorobenzyl (4-((6-methylpyridin-
			3-yl)methyl)phenyl)carbamate. LRMS (ES) m/z: 351
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.26 (s,
			1H), 7.54 (dd, J = 8.1, 2.0 Hz, 1H), 7.45 (dd, J = 8.1, 5.6
			Hz, 2H), 7.38 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 8.0 Hz,
			1H), 7.18-6.99 (m, 4H), 5.15 (s, 2H), 3.92 (s, 2H), 2.49
			(s, 3H).
328	5- (chloromethyl)- 2-methylpyridine	(4- (difluoromethyl) phenyl) methanol
			Compound 328: (4-(difluoro-13-methyl)phenyl)methyl
			(4-((6-methylpyridin-3-yl)methyl)phenyl)carbamate
			LRMS (ES) m/z: 383 [M + H]+. 1H NMR (400 MHz,
			Methanol-d4) δ 8.27 (s, 1H), 7.60-7.50 (m, 5H), 7.39 (d,
			J = 8.1 Hz, 2H), 7.23 (d, J = 8.0 Hz, 1H), 7.17-7.06 (m,
			2H), 6.77 (d, J = 56 Hz, 1H), 5.23 (s, 2H), 3.93 (s, 2H),
			2.50 (s, 3H).
65	5- (chloromethyl)- 2-methylpyridine	(1H- pyrazol-4- yl)methanol
			Compound 65: (1H-pyrazol-4-yl)methyl (4-((6-
			methylpyridin-3-yl)methyl)phenyl)carbamate. LRMS
			(ES) m/z: 323 [M + H]+. 1H NMR (400 MHz, Methanol-
			d4) δ 8.31 (s, 1H), 7.70 (s, 2H), 7.66 (dd, J = 8.1, 2.0 Hz,
			1H), 7.38 (d, J = 8.1 Hz, 2H), 7.30 (d, J = 8.1 Hz, 1H),
			7.13 (d, J = 8.1 Hz, 2H), 5.11 (s, 2H), 3.94 (s, 2H), 2.53
			(s, 3H).
292	5- (chloromethyl)- 2-methylpyridine	(4- chlorophenyl) methanol
			Compound 292: 4-chlorobenzyl (4-((6-methylpyridin-
			3-yl)methyl)phenyl)carbamate. LRMS (ES) m/z: 367
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.27 (s, 1H),
			7.55 (d, J = 8.2 Hz, 1H), 7.46-7.30 (m, 6H), 7.23 (d, J =
			8.1 Hz, 1H), 7.14 (d, J = 8.1 Hz, 2H), 5.16 (s, 2H), 3.93 (s,
			2H), 2.50 (s, 3H).
25	6- methylnicotinic acid	oxazol-5- ylmethanol
			Compound 25: oxazol-5-ylmethyl (4-((6-
			methylnicotinamido)methyl)phenyl)carbamate. LRMS
			(ES) m/z: 367 [M + H]+. 1H NMR (400 MHz, Methanol-
			d4) δ 8.88 (s, 1H), 8.23 (s, 1H), 8.15 (dd, J = 8.2, 2.2 Hz,
			1H), 7.42 (t, J = 7.1 Hz, 3H), 7.38-7.28 (m, 2H), 7.25 (s,
			1H), 5.25 (s, 2H), 4.54 (s, 2H), 2.60 (s, 3H).
66	6- methylnicotinic acid	thiazol-5- ylmethanol
			Compound 66: thiazol-5-ylmethyl (4-((6-
			methylnicotinamido)methyl)phenyl)carbamate.
			LRMS (ES) m/z: 383 [M + H]+. 1H NMR (400 MHz,
			Methanol-d4) δ (s 8 9.03 (s, 1H), 8.89 (s, 1H), 8.16 (d, J =
			8.3 Hz, 1H), 7.96 (s, 1H), 7.42 (q, J = 6.7 Hz, 3H), 7.31
			(d, J = 8.1 Hz, 2H), 5.43 (s, 2H), 4.54 (s, 2H), 2.61 (s, 3H).
227	6- methylnicotinic acid	(4- fluorophenyl) methanol
			Compound 227: 4-fluorobenzyl (4-((6-
			methylnicotinamido)methyl)phenyl)carbamate.
			LRMS (ES) m/z: [M + H]+. 1H NMR (400 MHz,
			Methanol-d4) δ 8.88 (s, 1H), 8.16 (d, J = 8.2 Hz, 1H),
			8.12 (s, 1H), 7.55-7.37 (m, 5H), 7.30 (d, J = 8.3 Hz,
			2H), 7.11 (t, J = 8.6 Hz, 2H), 5.16 (s, 2H), 4.54 (s, 2H),
			2.60 (s, 3H).
53	6- methylnicotinic acid	(4- methoxyphenyl) methanol
			Compound 53: (4-methoxyphenyl)methyl N-(4-{[(6-
			methylpyridin-3-
			yl)formamido]methyl}phenyl)carbamate. LCMS-ESI
			(POS.) m/z: 406.0 [M + H]+. 1H NMR (300 MHz, DMSO-
			d6) δ 9.65 (s, 1H), 9.06 (s, 1H), 8.92 (d, J = 2.8 Hz, 1H),
			8.16-8.07 (m, 1H), 7.46-7.31 (m, 5H), 7.28-7.19 (m,
			2H), 7.00-6.90 (m, 2H), 5.06 (d, J = 2.0 Hz, 2H), 4.42 (d,
			J = 6.0 Hz, 2H), 3.76 (d, J = 1.9 Hz, 3H), 2.50 (s, 3H).
133	6- methylnicotinic acid	(4- (difluoromethyl) phenyl) methanol
			Compound 133: (4-(difluoro-13-methyl)phenyl)methyl
			(4-((6-methylnicotinamido)methyl)phenyl)carbamate
			LRMS (ES) m/z: 426 [M + H]+. 1H NMR (400 MHz,
			Methanol-d4) δ 8.89 (s, 1H), 8.21-8.08 (m, 1H), 7.56 (m,
			4H), 7.43 (t, J = 9.0 Hz, 3H), 7.31 (d, J = 8.1 Hz, 2H), 6.77
			(t, J = 56 Hz, 1H), 5.25 (s, 2H), 4.54 (s, 2H), 2.61 (s, 3H).
275	6- methylnicotinic acid	(4- (difluoromethoxy) phenyl) methanol
			Compound 275: (4-(difluoro-13-methyl)phenyl)methyl
			(4-((6-methylnicotinamido)methyl)phenyl)carbamate
			LRMS (ES) m/z: 442 [M + H]+. 1H NMR (400 MHz,
			Methanol-d4) δ 8.89 (s, 1H), 8.21-8.08 (m, 1H), 7.56 (m,
			5H), 7.43 (t, J = 9.0 Hz, 2H), 7.31 (d, J = 8.1 Hz, 2H), 6.77
			(t, J = 56 Hz, 1H), 5.25 (s, 2H), 4.54 (s, 2H), 2.61 (s, 3H).
9	6- methylnicotinic acid	(1H- pyrazol-4- yl)methanol
			Compound 9: (1H-pyrazol-4-yl)methyl (4-((6-
			methylnicotinamido)methyl)phenyl)carbamate.
			LRMS (ES) m/z: 366 [M + H]+. 1H NMR (400 MHz,
			Methanol-d4) δ 8.88 (s, 1H), 8.15 (dd, J = 8.1, 2.3 Hz,
			1H), 7.70 (s, 2H), 7.41 (t, J = 6.3 Hz, 3H), 7.29 (d, J =
			8.1 Hz, 2H), 5.12 (s, 2H), 4.54 (d, J = 5.0 Hz, 2H), 2.60
			(d, J = 2.1 Hz, 3H).
37	6- methylnicotinic acid	pyridin-4- ylmethanol
			Compound 37: pyridin-4-ylmethyl (4-((6-
			methylnicotinamido)methyl)phenyl)carbamate.
			LRMS (ES) m/z: 377 [M + H]+. 1H NMR (400 MHz,
			Methanol-d4) δ 8.9 (s, 1H), 8.54 (d, J = 5.0 Hz, 2H), 8.16
			(dd, J = 8.1, 2.0 Hz, 1H), 7.58-7.37 (m, 5H), 7.31 (d, J =
			8.2 Hz, 2H), 5.26 (s, 2H), 4.54 (s, 2H), 2.60 (s, 3H).

Method 4: Synthesis of Carbamates by Phenol Replacement

Example I

Preparation of oxazol-5-ylmethyl (R)-(4-((2-(pyridin-3-yl)pyrrolidin-1-yl)methyl)phenyl)carbamate (Compound 6)

Step 1: Synthesis of phenyl N-(4-formylphenyl)carbamate

To a solution of 4aminobenzaldehyde (5 g, 4.8 mmol, 1.00 eq.) in THF (100 mL and H₂O (10 mL) at −5° C. was added K₂CO₃ (11.4 g, 82.4 mmol, 2.00 eq.) and phenyl chloroformate (9.7 g, 61.96 mmol, 1.50 eq.) dropwise over 15 min. The resulting mixture was stirred at 40° C. for 1 h. The resulting mixture was cooled to r.t., added water (50 mL), extracted twice with EtOAc (40 mL). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na₂SO₄, concentrated under reduced pressure, purified by silica gel column chromatography, and eluted with hexane/EtOAc (10:1) to afford phenyl N-(4-formylphenyl)carbamate (10.9 g, 93.1%) as a yellow solid. LRMS (ES) m/z: 242 [M+H]⁺.

Step 2: Synthesis of phenyl N-(4-{[(2R)-2-(pyridin-3-yl)pyrrolidin-1-yl]methyl}phenyl)carbamate

To a stirred solution of phenyl N-(4-formylphenyl)carbamate (720 mg, 2.99 mmol, 1.1 eq.) and (R)-3-(pyrrolidin-2-yl)pyridine (402 mg, 2.71 mmol, 1 eq.) in DCE (8 mL) was added STAB (1150 mg, 5.43 mmol, 2 eq.). The resulting mixture was stirred at r.t. for 2 h. The resulting mixture was added water (10 mL), extracted twice with CH₂Cl₂ (20 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na₂SO₄, concentrated under reduced pressure, purified by silica gel column chromatography, eluted with hexane/EtOAc (5:1) to afford phenyl N-(4-{[(2R)-2-(pyridin-3-yl)pyrrolidin-1-yl]methyl}phenyl)carbamate (700 mg, 67.0%) as a yellow solid. LRMS (ES) m/z: 374 [M+H]⁺.

Step 3: Synthesis of oxazol-5-ylmethyl (R)-(4-((2-(pyridin-3-yl)pyrrolidin-1-yl)methyl)phenyl)carbamate

To a stirred solution of phenyl N-(4-{[(2R)-2-(pyridin-3-yl)pyrrolidin-1-yl]methyl}phenyl)carbamate (70 mg, 0.19 mmol, 1 equiv) in THF (1 mL) was added 1,3-oxazol-5-ylmethanol (22 mg, 0.22 mmol, 1.18 equiv) and TEA (56 mg, 0.55 mmol, 2.95 equiv) at room temperature. The resulting mixture was stirred at 60° C. overnight. The mixture was allowed to cool down to room temperature. The crude product was purified by Prep-HPLC with the following conditions (2 #SHIMADZU (HPLC-01)): Column, XBridge Prep OBD C18 Column, 30*150 mm, 5 μm; mobile phase, Water (10 mmol/L NH4HCO₃+0.1% NH3·H₂O) and ACN (33% ACN up to 47% in 8 min); Detector, uv 254 nm to afford 5.1 mg of 1,3-oxazol-5-ylmethyl N-(4-{[(2R)-2-(pyridin-3-yl)pyrrolidin-1-yl]methyl}phenyl)carbamate as a white solid. LRMS (ES) m/z: 379 [M+H]⁺. 1H NMR (300 MHz, DMSO-d6) δ 9.75 (s, 1H), 8.59 (d, J=2.2 Hz, 1H), 8.50-8.39 (m, 2H), 7.84 (dt, J=7.9, 2.0 Hz, 1H), 7.43-7.33 (m, 3H), 7.30 (s, 1H), 7.14 (d, J=8.3 Hz, 2H), 5.20 (s, 2H), 3.58 (d, J=13.1 Hz, 1H), 3.43 (t, J=8.1 Hz, 1H), 3.05 (d, J=13.1 Hz, 1H), 2.96 (td, J=9.2, 8.3, 3.0 Hz, 1H), 2.20 (q, J=8.7 Hz, 2H), 1.77 (d, J=9.9 Hz, 2H), 1.60 (dq, J=18.0, 10.1, 8.1 Hz, 1H).

Compounds in the following table were prepared in a similar manner as Compound 6, using the amine and alcohol as listed.

Co#	Amine	Alcohol	Structure, Name and Data
1	(R)-3- (pyrrolidin- 2-yl) pyridine	(4- methoxyphenyl) methanol
			Compound 1: (4-methoxyphenyl)methyl N-(4-
			{[(2R)-2-(pyridin-3-yl)pyrrolidin-1-
			yl]methyl}phenyl)carbamate. LCMS-ESI (POS.)
			m/z: 418.0 [M + H]+. 1H NMR (300 MHz, DMSO-d6)
			δ 9.64 (s, 1H), 8.59 (dd, J = 2.3, 0.8 Hz, 1H), 8.46 (dd,
			J = 4.7, 1.7 Hz, 1H), 7.84 (dt, J = 7.8, 2.0 Hz, 1H), 7.43-
			7.30 (m, 5H), 7.12 (d, J = 8.4 Hz, 2H), 7.00-6.90
			(m, 2H), 5.05 (s, 2H), 3.75 (s, 3H), 3.58 (d, J = 13.0
			Hz, 1H), 3.43 (t, J = 8.1 Hz, 1H), 3.04 (d, J = 13.1 Hz,
			1H), 3.00-2.89 (m, 1H), 2.18 (t, J = 8.8 Hz, 2H), 1.76
			(d, J = 9.1 Hz, 2H), 1.58 (d, J = 9.0 Hz, 1H).
3	(R)-3- (pyrrolidin- 2-yl) pyridine	pyridin-4- ylmethanol
			Compound 3: pyridin-4-ylmethylN-(4-{[(2R)-2-
			(pyridin-3-yl)pyrrolidin-1-
			yl]methyl}phenyl)carbamate.LCMS-ESI (POS.)
			m/z: 389.0 [M + H]+. 1H NMR (300 MHz, DMSO-d6) δ
			9.85 (s, 1H), 8.63-8.54 (m, 3H), 8.46 (dd, J = 4.7, 1.7
			Hz, 1H), 7.84 (dt, J = 7.8, 2.0 Hz, 1H), 7.43-7.33 (m,
			5H), 7.15 (d, J = 8.4 Hz, 2H), 5.19 (s, 2H), 3.59 (d, J =
			13.1 Hz, 1H), 3.43 (t, J = 8.1 Hz, 1H), 3.05 (d, J = 13.1
			Hz, 1H), 2.96 (t, J = 6.9 Hz, 1H), 2.20 (q, J = 8.9 Hz,
			2H), 1.78 (s, 2H), 1.69-1.53 (m, 1H).
2	(R)-3- (pyrrolidin- 2-yl) pyridine	4- (hydroxymethyl) benzamide
			Compound 2: (4-carbamoylphenyl)methyl N-(4-
			{[(2R)-2-(pyridin-3-yl)pyrrolidin-1-
			yl]methyl}phenyl)carbamate. LCMS-ESI (POS.)
			m/z: 431.0 [M + H]+. 1H NMR (300 MHz, DMSO-d6) δ
			9.75 (s, 1H), 8.63-8.56 (m, 1H), 8.46 (dd, J = 4.7, 1.7
			Hz, 1H), 8.01-7.94 (m, 1H), 7.93-7.79 (m, 3H), 7.52-
			7.43 (m, 2H), 7.43-7.32 (m, 4H), 7.14 (d, J = 8.4
			Hz, 2H), 5.19 (s, 2H), 3.58 (d, J = 13.1 Hz, 1H), 3.43
			(t, J = 8.1 Hz, 1H), 3.05 (d, J = 13.1 Hz, 1H), 3.01-
			2.89 (m, 1H), 2.20 (q, J = 8.8 Hz,2H), 1.78 (s, 2H),
			1.69-1.50 (m, 1H).
5	(R)-3- (pyrrolidin- 2-yl) pyridine	1,4- phenylene- dimethanol
			Compound 5: [4-(hydroxymethyl)phenyl]methyl N-
			(4-{[(2R)-2-(pyridin-3-yl)pyrrolidin-1-
			yl]methyl}phenyl)carbamate. LCMS-ESI (POS.)
			m/z: 418.0 [M + H]+. 1H NMR (300 MHz, DMSO-d6) δ
			9.68 (s, 1H), 8.59 (d, J = 2.2 Hz, 1H), 8.46 (dd, J = 4.7,
			1.7 Hz, 1H), 7.84 (dt, J = 7.9, 2.0 Hz, 1H), 7.43-7.28
			(m, 7H), 7.13 (d, J = 8.5 Hz, 2H), 5.19 (t, J = 5.7 Hz,
			1H), 5.11 (s, 2H), 4.49 (d, J = 5.7 Hz, 2H), 3.58 (d, J =
			13.1 Hz, 1H), 3.43 (t, J = 8.1 Hz, 1H), 3.04 (d, J = 13.1
			Hz, 1H), 2.95 (t, J = 7.2 Hz, 1H), 2.20 (q, J = 8.8 Hz,
			2H), 1.78 (m, 2H), 1.59 (m, 1H).
168	1-(4- amino- benzyl)-4- methyl- piperazin- 2-one	(4- methoxyphenyl) methanol
			Compound 168: (4-methoxyphenyl)methyl N-{4-
			[(4-methyl-2-oxopiperazin-1-
			yl)methyl]phenyl}carbamate. LCMS-ESI (POS.)
			m/z: 384.0 [M + H]+. 1H NMR (300 MHz, DMSO-d6)
			δ 9.69 (s, 1H), 7.39 (dd, J = 15.0, 8.1 Hz, 4H), 7.13 (d,
			J = 8.1 Hz, 2H), 6.95 (d, J = 8.2 Hz, 2H), 5.07 (s, 2H),
			4.43 (s, 2H), 3.76 (s, 3H), 3.15 (t, J = 5.6 Hz, 2H), 2.99
			(s, 2H), 2.55 (d, J = 5.5 Hz, 2H), 2.20 (s, 3H).
222	3- (methyl- sulfonyl) azetidine	(4- chlorophenyl) methanol
			Compound 222: (4-chlorophenyl)methyl N-{4-[(3-
			methanesulfonylazetidin-1-
			yl)methyl]phenyl}carbamate. LCMS-ESI (POS.)
			m/z: 410.0 [M + H]+. 1H NMR (300 MHz, DMSO-d6) δ
			9.76 (s, 1H), 7.42 (d, J = 21.8 Hz, 6H), 7.17 (d, J = 8.5
			Hz, 2H), 5.13 (s, 2H), 4.13 (p, J = 7.2 Hz, 1H), 3.44 (d,
			J = 8.0 Hz, 2H), 3.38-3.28 (m, 4H), 2.94 (s, 3H).
324	3- (methyl- sulfonyl) azetidine	(4- methoxyphenyl) methanol
			Compound 324: (4-methoxyphenyl)methyl N-{4-
			[(3-methanesulfonylazetidin-1-
			yl)methyl]phenyl}carbamate. LCMS-ESI (POS.)
			m/z: 405.1 [M + H]+. 1H NMR (300 MHz, DMSO-d6) δ
			9.67 (s, 1H), 7.36 (m, 4H) 7.15 (d, J = 8.5 Hz, 2H), 6.93
			(d, J = 8.5 Hz, 2H), 5.06 (s, 2H), 4.13 (p, J = 7.2 Hz,
			1H), 3.75 (s, 3H), 3.54-3.40 (m, 4H), 3.35 (m, 2H),
			2.94 (s, 3H).
228	(S)-3- amino-1- methyl- pyrrolidin- 2-one	(4- chlorophenyl) methanol
			Compound 228: 4-chlorobenzyl (S)-(4-(((1-methyl-
			2-oxopyrrolidin-3-
			yl)amino)methyl)phenyl)carbamate. LRMS (ES)
			m/z: 388 [M + H]+. 1HNMR (300 MHz, DMSO-d6) δ
			9.72 (s, 1H), 7.42 (m, 6H), 7.23 (d, J = 8.4 Hz, 2H),
			5.13 (s, 2H), 3.71 (d, J = 6.0 Hz, 2H), 3.29-3.11 (m,
			3H), 2.71 (s, 3H), 2.27 (s, 1H), 2.20-2.05 (m, 1H),
			1.63 (dq, J = 12.1, 8.7 Hz, 1H).
284	1- methyl- piperazin- 2-one	(4- chlorophenyl) methanol
			Compound 284: (4-chlorophenyl)methyl N-{4-[(4-
			methyl-3-oxopiperazin-1-
			yl)methyl]phenyl}carbamate. LCMS-ESI (POS.)
			m/z: 388.0 [M + H]+. 1H NMR (400 MHz, DMSO-d6) δ
			9.80 (s, 1H), 7.45 (d, J = 10.6 Hz, 5H), 7.30 (s, 1H),
			7.21 (d, J = 8.1 Hz, 2H), 5.14 (s, 2H), 3.44 (s, 2H), 3.23
			(t, J = 5.4 Hz, 2H), 2.91 (s, 2H), 2.80 (s, 3H), 2.59 (t,
			J = 5.5 Hz, 2H).
325	1- methyl- piperazin- 2-one	(4- methoxyphenyl) methanol
			Compound 325: (4-methoxyphenyl)methyl N-{4-
			[(4-methyl-3-oxopiperazin-1-
			yl)methyl]phenyl}carbamate. LCMS-ESI (POS.)
			m/z: 384.0 [M + H]+. 1H NMR (300 MHz, DMSO-d6) δ
			9.69 (s, 1H), 7.39 (dd, J = 15.4, 8.4 Hz, 4H), 7.20 (d,
			J = 8.3 Hz, 2H), 6.99-6.90 (m, 2H), 5.06 (s, 2H), 3.75
			(s, 3H), 3.44 (s, 2H), 3.33-3.18 (m, 2H), 2.90 (s, 2H),
			2.80 (s, 3H), 2.59 (t, J = 5.6 Hz, 2H).
	tert- butyl piperazine- 1- carboxylate	(4- chlorophenyl) methanol
			Intermediate 25.1: tert-butyl 4-(4-((((4-
			chlorobenzyl)oxy)carbonyl)amino)benzyl)piperazine-
			1-carboxylate. LRMS (ES) m/z: 404 [M + H-tBu]+.
	tert- butyl piperazine- 1- carboxylate	(4- methoxyphenyl) methanol
			Intermediate 26.1: tert-butyl 4-(4-((((4-
			methoxybenzyl)oxy)carbonyl)amino)benzyl)
			piperazine-1-carboxylate. LRMS (ES) m/z: 400 [M + H-
			tBu]+.
341	(S)- pyrrolidin- 2- ylmethanol	(4- methoxyphenyl) methanol
			Compound 341: (4-methoxyphenyl)methyl N-{4-
			[(2S)-1-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-1-
			oxopropan-2-yl]phenyl}carbamate LCMS-ESI
			(POS.) m/z: 413.0 [M + H]+. 1H NMR (400 MHz,
			DMSO-d6) δ 9.64 (s, 1H), 7.36 (dd, J = 8.7, 3.3 Hz,
			4H), 7.21-7.09 (m, 2H), 6.99-6.90 (m, 2H), 5.06 (s,
			2H), 4.70 (dd, J = 6.3, 4.7 Hz, 1H), 3.98 (d, J = 6.8 Hz,
			1H), 3.90-3.78 (m, 1H), 3.75 (s, 3H), 3.53-3.34 (m,
			2H), 3.05 (dd, J = 9.9, 6.0 Hz, 2H), 1.76 (d, J = 3.9 Hz,
			3H), 1.24 (dd, J = 15.6, 6.9 Hz, 3H).
47	(S)- pyrrolidin- 2- ylmethanol	(4- methoxyphenyl) methanol
			Compound 47: {[4-(1,1-dioxothietan-3-
			yl)phenyl]amino}-N-[(4-
			methoxyphenyl)methyl]carboxamide. LCMS-ESI
			(POS.) m/z: 413.0 [M + H]+. 1HNMR (400 MHz,
			DMSO-d6) δ 9.64 (s, 1H), 7.41-7.31 (m, 4H), 7.15 (d,
			J = 8.6 Hz, 2H), 6.99-6.90 (m, 2H), 5.05 (s, 2H), 4.77
			(dt, J = 20.2, 5.7 Hz, 1H), 3.89 (s, 1H), 3.80 (t, J = 6.8
			Hz, 1H), 3.75 (s, 3H), 3.51 (dd, J = 9.9, 5.4 Hz,
			2H),3.29(d, J = 8.2 Hz, 1H), 3.06 (q, J = 8.2 Hz, 1H),
			1.88-1.76 (m, 2H), 1.63 (d, J = 8.2 Hz, 3H), 1.25 (d,
			J = 6.8 Hz, 3H).

Suzuki Coupling

Example J

Preparation of 4-chlorobenzyl (4-(thiazol-2-ylmethyl)phenyl)carbamate (Compound 336)

Step 1: Synthesis of 4-chlorobenzyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate

To a mixture of 4-chlorobenzyl (4-bromophenyl)carbamate (2.04 g, 6.00 mmol, 1.00 equiv), bis(pinacolato)diboron (2.29 g, 9.00 mmol, 1.50 equiv) in dioxane (20 mL) was added KOAc (0.88 g, 9.00 mmol, 1.50 equiv), PdCl₂(dppf) (0.44 g, 0.60 mmol, 0.10 equiv). The resulting mixture was degassed for 10 min. Then it was heated at MW at 130° C. for 60 min. The reaction mixture was extracted with EtOAc (100 mL) and brine (50 mL). The organic layer was concentrated and purified on silica gel with 25% EtOAc/Hex to afford the desired product 4-chlorobenzyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate as a yellowish solid (1.25 g, 54%). LRMS (ES) m/z: 388 [M+H]⁺.

Step 2: Synthesis of 4-chlorobenzyl (4-(thiazol-2-ylmethyl)phenyl)carbamate

To a mixture of 4-chlorobenzyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate (78 mg, 0.20 mmol, 1.00 equiv), 2-(chloromethyl)thiazole (40 mg, 0.30 mmol, 1.50 equiv), Cs₂CO₃ (77 mg, 0.24 mmol, 1.20 equiv) in dioxane (2 mL) and H₂O (1 mL) was added PdCl₂(dppf) (15 mg, 0.02 mmol, 0.10 equiv). The resulting mixture was degassed for 2 min. Then it was heated at 130° C. at MW for 30 min. The mixture was extracted with EtOAc (0 mL) and brine (3 mL). The organic layer was concentrated and purified by Prep-HPLC with the following conditions (Column: XBridge Prep OBD C18 Column 30×150 mm 5 um; Mobile Phase A:Water (0.1% formic acid), Mobile Phase B: MeCN (0.1% formic acid; Flow rate: 20 mL/min) to afford 4-chlorobenzyl (4-(thiazol-2-ylmethyl)phenyl)carbamate (21 mg, 29%) as a white solid. LRMS (ES) m/z: 359 [M+H]3. ¹H NMR (400 MHz, Methanol-d₄) δ 7.70 (d, J=3.4 Hz, 1H), 7.52-7.33 (m, 6H), 7.33-7.16 (m, 2H), 5.17 (s, 2H), 4.31 (s, 2H).

Compounds in the following table were prepared in a similar manner as Compound 336, using the intermediates and chlorides as listed.

Co#	Intermediate	Chloride	Structure, Name and Data
314	27.1	5-(chloromethyl)- 1-methyl- 1H-pyrazole
			Compound 314: 4-chlorobenzyl (4-
			((1-methyl-1H-pyrazol-5-
			yl)methyl)phenyl)carbamate LRMS
			(ES) m/z: 356[M + H]+. 1H NMR (400
			MHz, Methanol-d4) δ 7.48-7.34 (m,
			7H), 7.21-6.93 (m, 2H), 6.05 (d, J =
			1.9 Hz, 1H), 5.17 (s, 2H), 4.01 (s, 2H),
			3.71 (s, 3H).
351	27.1	5-(chloromethyl)thiazole
			Compound 351: 4-chlorobenzyl (4-
			(thiazol-5-
			ylmethyl)phenyl)carbamate LRMS
			(ES) m/z: 359 [M + H]+. 1H NMR (400
			MHz, Methanol-d4) δ 8.85 (s, 1H), 7.75-
			7.65 (m, 1H), 7.48-7.32 (m, 6H),
			7.30-7.07 (m, 2H), 5.17 (s, 2H), 4.18
			(s, 2H).
303	27.1	2-(chloromethyl)pyrazine
			Compound 303: 4-chlorobenzyl (4-
			(pyrazin-2-
			ylmethyl)phenyl)carbamate LRMS
			(ES) m/z: 354 [M + H]+. 1H NMR (400
			MHz, Methanol-d4) δ 8.53 (d, J = 1.6
			Hz, 2H), 8.45 (d, J = 2.2 Hz, 1H), 7.50-
			7.33 (m, 6H), 7.33-6.99 (m, 2H),
			5.16 (s, 2H), 4.14 (s, 2H).
350	27.1	5-(chloromethyl) isothiazole
			Compound 350: 4-chlorobenzyl (4-
			(isothiazol-5-
			ylmethyl)phenyl)carbamate LRMS
			(ES) m/z: 359 [M + H]+. 1H NMR (400
			MHz, Methanol-d4) δ 8.37 (d, J = 1.6
			Hz, 1H), 7.41 (m, 6H), 7.24 (d, J = 8.3
			Hz, 2H), 7.13 (d, J = 1.6 Hz, 1H), 5.18
			(s, 2H), 4.28 (s, 2H).
353	27.1	4-(chloromethyl)oxazole
			Compound 353: 4-chlorobenzyl (4-
			(oxazol-4-ylmethyl)phenyl) LRMS
			(ES) m/z: 343 [M + H]+. 1H NMR (400
			MHz, Methanol-d4) δ 8.14 (s, 1H), 7.62
			(d, J = 1.2 Hz, 1H), 7.38 (dd, J = 9.6,
			5.2 Hz, 6H), 7.19 (d, J = 8.3 Hz, 2H),
			5.16 (s, 2H), 3.84 (s, 2H).
279	27.1	2-(chloromethyl) pyrimidine
			Compound 279: 4-chlorobenzyl (4-
			(pyrimidin-2-
			ylmethyl)phenyl)carbamate. LRMS
			(ES) m/z: 354.1 [M + H]+. 1H NMR (400
			MHz, Methanol-d4) δ 8.73 (d, J = 5.0 Hz,
			2H), 7.45-7.31 (m, 7H), 7.24 (d, J = 8.3
			Hz, 2H), 5.15 (s, 2H), 4.21 (s, 2H).

Amine Deprotection

Example K

Preparation of 4-chlorobenzyl (4-(piperidin-4-ylmethyl)phenyl)carbamate hydrochloride (Compound 231/Intermediate 6.2)

To a solution of tert-butyl 4-(4-((((4-chlorobenzyl)oxy)carbonyl)amino)benzyl)piperidine-1-carboxylate (1.30 g, 2.84 mmol, 1.00 equiv) in MeOH (2 mL) at 0° C. was added 4M HCl/Dioxane (8.52 mL, 34.08 mmol, 12 equiv) slowly. The resulting mixture was warmed up to rt and stirred for 1 h. The solvents were removed and the residue 4-chlorobenzyl (4-(piperidin-4-ylmethyl)phenyl)carbamate hydrochloride was used directly in the next steps without further purification. LRMS (ES) m/z: 359 [M+H]⁺.

Compounds in the following table were prepared in a similar manner as Compound 231/intermediate 6.2, using the intermediates as listed.

Co	Inter-
#	mediate	Structure, Name and Data
	7.1
		Intermediate 7.2: 4-chlorobenzyl (4-(piperidin-4-
		yl)phenyl)carbamate. LCMS-APCI (POS.) m/z: 345.1 [M + H]+.
320	8.1
		Compound 320/Intermediate 8.2: oxazol-5-ylmethyl (4-(piperidin-
		4-ylmethyl)phenyl)carbamate. LRMS (ES) m/z: 316.1 [M + H]+. 1H
		NMR (400 MHz, Methanol-d4) δ 8.46 (s, 1H), 8.24 (s, 1H), 7.38 (d, J =
		8.0 Hz, 2H), 7.25 (s, 1H), 7.13 (d, J = 8.1 Hz, 2H), 5.25 (s, 2H), 3.37 (d,
		J = 12.5 Hz, 2H), 2.93 (td, J = 13.0, 2.7 Hz, 2H), 2.58 (d, J = 6.6 Hz, 2H),
		2.00-1.79 (m, 2H), 1.43 (qd, J = 11.9, 6.0 Hz, 2H).
	9.1
		Intermediate 9.2: oxazol-5-ylmethyl (4-(piperidin-4-
		yl)phenyl)carbamate. LRMS (ES) m/z: 302.1 [M + H]+.
	10.1
		Intermediate 10.2: pyridin-4-ylmethyl (4-(piperidin-4-
		ylmethyl)phenyl)carbamate. LCMS-APCI (POS.) m/z: 326.1
		[M + H]+.
252	11.1
		Compound 252/Intermediate 11.2: oxazol-5-ylmethyl (4-(2-
		(piperidin-4-yl)ethyl)phenyl)carbamate hydrochloride. LRMS (ES)
		m/z: 330.1 [M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
		8.89 (s, 1H), 8.66 (s, 1H), 8.43 (s, 1H), 7.35 (d, J = 8.1 Hz, 2H), 7.30 (s,
		1H), 7.18-7.02 (m, 2H), 5.21 (s, 2H), 3.21 (d, J = 12.6 Hz, 2H), 2.79
		(q, J = 12.0 Hz, 2H), 2.53 (m, 2H), 1.82 (d, J = 13.6 Hz, 2H), 1.49 (t,
		J = 6.5 Hz, 3H), 1.41-1.24 (m, 2H).
	13.1
		Intermediate 13.2: 4-chlorobenzyl (4-((piperidin-4-
		yloxy)methyl)phenyl)carbamate.
		LCMS-APCI (POS.) m/z: 375. [M + H]+.
	14.1
		Intermediate 14.2: 4-chlorobenzyl (4-((azetidin-3-
		yloxy)methyl)phenyl)carbamate. LCMS-APCI (POS.) m/z: 347.1
		[M + H]+.
	15.1
		Intermediate 15.2: (4-chlorophenyl)methyl N-[4-
		(aminomethyl)phenyl]carbamate. LCMS-ESI (NEG.) m/z: 289.0
		[M − H]−.
	16.1
		Intermediate 16.2: (1S)-1-[4-({[(4-
		chlorophenyl)methoxy]carbonyl}amino)phenyl]ethanaminium
		chloride. LCMS-APCI (POS.) m/z: 288.0 [M + H—NH3]+.
	17.1
		Intermediate 17.2: (4-chlorophenyl)methyl N-{4-
		[(methylamino)methyl]phenyl}carbamate. LCMS-ES (POS.) m/z:
		305.0 [M + H]+.
	18.1
		Intermediate 18.2: 4-chlorobenzyl (S)-(4-(1-
		(methylamino)ethyl)phenyl)carbamate. LCMS-ES (POS.) m/z: 319.0
		[M + H]+.
	19.1
		Intermediate 19.2: 1,3-oxazol-5-ylmethyl N-[4-
		(aminomethyl)phenyl]carbamate. LCMS-ESI (POS.) m/z: 231.0
		[M + H—NH3]+.
	20.1
		Intermediate 20.2: 1,3-oxazol-5-ylmethyl N-{4-[(1S)-1-
		aminoethyl]phenyl}carbamate. LCMS-APCI (POS.) m/z: 245.1
		[M + H—NH3]+. 1H NMR (400 MHz, DMSO-d6) δ 9.93 (s, 1H), 8.43 (s,
		1H), 8.35 (s, 3H), 7.48 (d, J = 8.2 Hz, 2H), 7.41 (d, J = 8.1 Hz, 2H), 7.31
		(s, 1H), 5.22 (s, 2H), 4.32 (p, J = 6.5 Hz, 1H), 1.48 (d, J = 6.7 Hz, 3H).
	25.1
		Intermediate 25.2: 4-chlorobenzyl (4-(piperazin-1-
		ylmethyl)phenyl)carbamate. LRMS (ES) m/z: 360.1[M + H]
	26.1
		Intermediate 26.2: 4-methoxybenzyl (4-(piperazin-1-
		ylmethyl)phenyl)carbamate. LRMS (ES) m/z: 356.1[M + H]+.
	29.1
		Intermediate 31.1: oxazol-5-ylmethyl (4-(2-azaspiro[3.3]heptan-6-
		yl)phenyl)carbamate
		LRMS (ES) m/z: 314.1 [M + H]+
	29.2
		Intermediate 30.1: oxazol-5-ylmethyl (3-fluoro-4-(6-
		azaspiro[3.4]octan-2-yl)phenyl)carbamate
		LRMS (ES) m/z: 346.1[M + H]+.
	29.3
		Intermediate 30.2: oxazol-5-ylmethyl (R)-(4-(piperidin-3-
		yl)phenyl)carbamate
		LRMS (ES) m/z: 301.1[M + H]+.
378	29.4
		Compound 378: oxazol-5-ylmethyl (4-((6-azaspiro[3.4]octan-2-
		yl)methyl)-3-fluorophenyl)carbamate
		LRMS (ES) m/z: 360.1[M + H]+.
		1H NMR (400 MHz, DMSO-d6) δ 9.98 (s, 1H), 8.45 (s, 1H), 8.36 (s,
		1H), 7.35-7.29 (m, 2H), 7.21-7.13 (m, 2H), 5.25 (s, 2H), 3.20 (s,
		2H), 3.09-3.05 (m, 2H), 2.97 (s, 1H), 2.03-1.87 (m, 4H), 1.85-1.69
		(m, 4H).
	29.5
		Intermediate 30.3: oxazol-5-ylmethyl (S)-(4-(piperidin-3-
		yl)phenyl)carbamate
		LRMS (ES) m/z: 302.1[M + H]+.
	29.6
		Intermediate 30.4: oxazol-5-ylmethyl (4-((2-azaspiro[3.3]heptan-6-
		yl)methyl)-3-fluorophenyl)carbamate
		LRMS (ES) m/z: 346.1[M + H]+.
	29.7
		Intermediate 30.4-a: oxazol-5-ylmethyl (3-fluoro-4-(2-
		azaspiro[3.3]heptan-6-yl)phenyl)carbamate
		LRMS (ES) m/z: 332.1[M + H]+.
	29.8
		Intermediate 30.5: oxazol-5-ylmethyl (3-fluoro-4-(2-
		azaspiro[3.3]heptan-6-yl)phenyl)carbamate
		LRMS (ES) m/z: 342.1[M + H]+.
	29.9
		Intermediate 30.6: oxazol-5-ylmethyl (3-fluoro-4-(piperidin-4-
		yl)phenyl)carbamate
		LRMS (ES) m/z: 320.1[M + H]+.
	29.10
		Intermediate 30.7: oxazol-5-ylmethyl (4-((4-azaspiro[2.5]octan-7-
		yl)methyl)phenyl)carbamate hydrochloride
		LRMS (ES) m/z: 342.1[M + H]+.
		1H NMR (400 MHz, DMSO-d6) δ 8.22 (s, 1H), 7.35 (d, J = 8.2 Hz, 2H),
		7.23 (s, 1H), 7.11 (d, J = 8.3 Hz, 2H), 5.23 (s, 2H), 4.58 (s, 2H), 3.04
		(td, J = 12.7, 2.90 Hz, 1H), 2.59 (d, J = 7.2 Hz, 2H), 2.12-1.77 (m,
		3H), 1.41 (qd, J = 12.5, 4.0 Hz, 1H), 1.32-1.22 (m, 1H), 1.00-0.87
		(m, 2H), 0.85-0.77 (m, 1H), 0.75-0.65 (m, 1H).
426	29.11
		Compound 426: oxazol-5-ylmethyl (4-((3-azabicyclo[3.2.1]octan-8-
		yl)methyl)phenyl)carbamate
		LRMS (ES) m/z: 342.1[M + H]+.
	29.12
		Intermediate 30.8: oxazol-5-ylmethyl (4-((3-
		azabicyclo[3.1.1]heptan-6-yl)methyl)phenyl)carbamate
		LRMS (ES) m/z: 328.1[M + H]+.
	9.1
		Intermediate 30.9: oxazol-5-ylmethyl (4-(piperidin-4-
		yl)phenyl)carbamate
		LRMS (ES) m/z: 302.1[M + H]+.
	8.1
		Intermediate 30.10: oxazol-5-ylmethyl (4-(piperidin-4-
		ylmethyl)phenyl)carbamate hydrochloride
		LRMS (ES) m/z: 316.1[M + H]+.
	29.15
		Intermediate 30.10: oxazol-5-ylmethyl (3-fluoro-4-(piperidin-4-
		ylmethyl)phenyl)carbamate hydrochloride
		LRMS (ES) m/z: 334.1[M + H]+.
	29.16
		Intermediate 30.11: oxazol-5-ylmethyl (4-((2-
		azabicyclo[4.1.0]heptan-5-yl)methyl)phenyl)carbamate
		hydrochloride
		LRMS (ES) m/z: 328.1[M + H]+.
	29.17
		Intermediate 30.12: thiazol-5-ylmethyl (4-(piperidin-4-
		ylmethyl)phenyl)carbamate.
		LRMS (ES) m/z: 332.1[M + H]+.

Amine Derivatization

Example L

Method A: Synthesis of 4-chlorobenzyl (4-((1-(oxetan-3-yl)piperidin-4-yl)methyl)phenyl)carbamate (Compound 43)

To a mixture of 4-chlorobenzyl (4-(piperidin-4-ylmethyl)phenyl)carbamate hydrochloride (79 mg, 0.20 mmol, 1.00 equiv), 3-oxetanone (29 mg, 0.40 mmol, 1.00 equiv) in DCM (1 mL) was added Na(OAc)₃BH (93 mg, 0.44 mmol, 2.20 equiv). The reaction mixture was stirred for 30 min, then concentrated under reduced pressure, purified by Prep-HPLC with the following conditions (Column: XBridge Prep OBD C18 Column 30×150 mm 5 um; Mobile Phase A:Water (0.1% formic acid), Mobile Phase B: MeCN (0.1% formic acid; Flow rate: 20 mL/min) to afford 4-chlorobenzyl (4-((1-(oxetan-3-yl)piperidin-4-yl)methyl)phenyl)carbamate (80 mg, 96%) as a white solid. LRMS (ES) m/z: 415 [M+H]⁺. ¹H NMR (400 MHz, Methanol-d₄) δ 7.39 (dd, J=15.4, 7.0 Hz, 6H), 7.11 (d, J=8.2 Hz, 2H), 5.17 (s, 2H), 4.77 (t, J=7.2 Hz, 2H), 4.69 (t, J=6.6 Hz, 2H), 3.92 (p, J=6.5 Hz, 1H), 3.12 (d, J=12.0 Hz, 2H), 2.57 (d, J=6.9 Hz, 2H), 2.44-2.25 (m, 2H), 1.81 (d, J=14.9 Hz, 3H), 1.41 (qd, J=12.8, 11.8, 3.7 Hz, 2H).

Method B: Synthesis of 4-chlorobenzyl (4-((1-acetylpiperidin-4-yl)methyl)phenyl)carbamate (Compound 40)

To a mixture of 4-chlorobenzyl (4-(piperidin-4-ylmethyl)phenyl)carbamate hydrochloride (0.20 g, 0.50 mmol, 1.00 equiv) in DCM (2 mL) was added DIEA (0.19 g, 1.50 mmol, 3.00 equiv), followed by acetic anhydride (0.10 g, 1.00 mmol, 2.00 equiv). The reaction mixture was stirred for 30 min, then concentrated under reduced pressure, purified by Prep-HPLC with the following conditions (Column: XBridge Prep OBD C18 Column 30×150 mm 5 um; Mobile Phase A:Water (0.1% formic acid), Mobile Phase B: MeCN (0.1% formic acid; Flow rate: 20 mL/min) to afford 4-chlorobenzyl (4-((1-acetylpiperidin-4-yl)methyl)phenyl)carbamate (138 mg, 69%) as a white solid. LRMS (ES) m/z: 401[M+H]⁺. ¹H NMR (400 MHz, Methanol-d₄) δ 7.48-7.28 (m, 6H), 7.10 (d, J=8.5 Hz, 2H), 5.17 (s, 2H), 4.49 (ddt, J=13.4, 4.6, 2.4 Hz, 1H), 3.89 (dp, J=13.6, 2.3 Hz, 1H), 3.04 (td, J=13.0, 2.7 Hz, 1H), 2.66-2.46 (m, 3H), 2.08 (s, 3H), 1.94-1.63 (m, 3H), 1.14 (dqd, J=37.1, 12.6, 4.3 Hz, 2H).

Method C. Synthesis of 4-chlorobenzyl (4-((1-isobutyrylpiperidin-4-yl)methyl)phenyl)carbamate (Compound 87)

Followed the same procedure as above. Obtained the desired product 4-chlorobenzyl (4-((1-isobutyrylpiperidin-4-yl)methyl)phenyl)carbamate as a white solid (30 mg, 70%). LRMS (ES) m/z: 429 [M+H]⁺. ¹H NMR (400 MHz, Methanol-d₄) δ 7.53-7.20 (m, 6H), 7.10 (d, J=8.2 Hz, 2H), 5.17 (s, 2H), 4.52 (d, J=13.4 Hz, 1H), 4.03 (d, J=13.9 Hz, 1H), 3.13-2.79 (m, 2H), 2.68-2.42 (m, 3H), 1.96-1.57 (m, 3H), 1.23-0.96 (m, 8H).

Method D. Synthesis of methyl 4-(4-((((4-chlorobenzyl)oxy)carbonyl)amino)benzyl)piperidine-1-carboxylate (Compound 98)

To a mixture of 4-chlorobenzyl (4-(piperidin-4-ylmethyl)phenyl)carbamate hydrochloride (79 mg, 0.20 mmol, 1.00 equiv) in DCM (2 mL) was added DIEA (52 mg, 0.40 mmol, 2.00 equiv), followed by methyl chloroformate (19 mg, 0.20 mmol, 1.00 equiv). The reaction mixture was stirred for 30 min, then concentrated under reduced pressure, purified by Prep-HPLC with the following conditions (Column: XBridge Prep OBD C18 Column 30×150 mm 5 um; Mobile Phase A:Water (0.1% formic acid), Mobile Phase B: MeCN (0.1% formic acid; Flow rate: 20 mL/min) to afford methyl 4-(4-((((4-chlorobenzyl)oxy)carbonyl)amino)benzyl)piperidine-1-carboxylate (76 mg, 91%) as a white solid. LRMS (ES) m/z: 417 [M+H]⁺. ¹H NMR (400 MHz, Methanol-d₄) δ 7.53-7.23 (m, 6H), 7.21-6.97 (m, 2H), 5.17 (s, 2H), 4.08 (d, J=13.1 Hz, 2H), 3.67 (s, 3H), 2.76 (s, 2H), 2.51 (d, J=7.1 Hz, 2H), 1.64 (d, J=13.7 Hz, 3H), 1.12 (qd, J=12.6, 4.4 Hz, 2H).

Method E. Synthesis of 4-chlorobenzyl (4-((1-(methylsulfonyl)piperidin-4-yl)methyl)phenyl)carbamate (Compound 38)

Followed the same procedure as above. Obtained the desired product 4-chlorobenzyl (4-((1-(methylsulfonyl) piperidin-4-yl)methyl)phenyl)carbamate (60 mg, 69%) as a white solid. LRMS (ES) m/z: 437 [M+H]⁺. ¹H NMR (400 MHz, Methanol-d₄) δ 7.39 (dq, J=11.5, 8.3, 7.9 Hz, 6H), 7.22-6.98 (m, 2H), 5.17 (s, 2H), 3.70 (d, J=11.5 Hz, 2H), 2.80 (s, 3H), 2.68 (td, J=12.0, 2.5 Hz, 2H), 2.55 (d, J=7.1 Hz, 2H), 1.75 (d, J=14.0 Hz, 3H), 1.38-1.16 (m, 2H).

Method F. Synthesis of 4-chlorobenzyl (4-((1-(N,N-dimethylsulfamoyl)piperidin-4-yl)methyl)phenyl)carbamate (Compound 34

Followed the same procedure as above. Obtained the desired product 4-chlorobenzyl (4-((1-(N,N-dimethylsulfamoyl)piperidin-4-yl)methyl)phenyl)carbamate (77 mg, 83%) as a white solid. LRMS (ES) m/z: 466 [M+H]⁺. ¹H NMR (400 MHz, Methanol-d₄) δ 7.49-7.24 (m, 6H), 7.20-7.04 (m, 2H), 5.17 (s, 2H), 3.65 (dp, J=12.4, 1.9 Hz, 2H), 2.79 (s, 8H), 2.53 (d, J=6.7 Hz, 2H), 1.76-1.51 (m, 3H), 1.34-1.12 (m, 2H).

Method G. Synthesis of 4-chlorobenzyl (4-((1-(dimethylcarbamoyl)piperidin-4-yl)methyl)phenyl)carbamate (Compound 58)

Followed the same procedure as above. Obtained the desired product 4-chlorobenzyl (4-((1-(dimethylcarbamoyl)piperidin-4-yl)methyl)phenyl)carbamate as a white solid (30 mg, 70%). LRMS (ES) m/z: 430 [M+H]⁺. ¹H NMR (400 MHz, Methanol-d₄) δ 7.52-7.26 (m, 6H), 7.10 (d, J=8.2 Hz, 2H), 5.17 (s, 2H), 3.65 (d, J=13.1 Hz, 2H), 2.83 (d, J=1.2 Hz, 6H), 2.73 (td, J=12.7, 2.3 Hz, 2H), 2.53 (d, J=6.9 Hz, 2H), 1.81-1.53 (m, 3H), 1.21 (qd, J=12.3, 4.0 Hz, 2H).

Method H. Synthesis of oxazol-5-ylmethyl (4-((1-(2,2-difluoroethyl)piperidin-4-yl)methyl)phenyl)carbamate (Compound 59)

To a solution of oxazol-5-ylmethyl (4-(piperidin-4-ylmethyl)phenyl)carbamate hydrochloride (70 mg, 0.20 mmol, 1.00 equiv), DIEA (77 mg, 0.60 mmol, 3.00 equiv) in DMF (2 mL), was added 2,2-difluoroethyl trifluoromethanesulfonate (86 mg, 0.40 mmol, 2.00 equiv). The reaction mixture was stirred at rt for 4 h. The mixture was purified by Prep-HPLC with the following conditions (Column: XBridge Prep OBD C18 Column 30×150 mm 5 um; Mobile Phase A:Water (0.1% formic acid), Mobile Phase B: MeCN (0.1% formic acid; Flow rate: 20 mL/min) to afford the desired product oxazol-5-ylmethyl (4-((1-(2,2-difluoro-213-ethyl)piperidin-4-yl)methyl)phenyl)carbamate as a white solid (35 mg, 46%). LRMS (ES) m/z: 380 [M+H]⁺. ¹H NMR (400 MHz, Methanol-d₄) δ 8.23 (d, J=2.1 Hz, 1H), 7.35 (d, J=7.9 Hz, 2H), 7.25 (d, J=2.0 Hz, 1H), 7.15-6.98 (m, 2H), 6.09 (t, J=56 Hz, 1H), 5.24 (d, J=2.2 Hz, 2H), 3.12 (d, J=11.7 Hz, 2H), 2.96 (tt, J=15.4, 2.9 Hz, 2H), 2.52 (d, J=6.9 Hz, 2H), 2.40 (t, J=12.0 Hz, 2H), 1.81-1.49 (m, 3H), 1.37 (q, J=12.0 Hz, 2H).

Method I. Preparation of (4-chlorophenyl)methyl N-(4-{[4-(pyrazin-2-yl)piperazin-1-yl]methyl}phenyl)carbamate (Compound 24)

A mixture of (4-chlorophenyl)methyl N-[4-(piperazin-1-ylmethyl)phenyl]carbamate; trifluoroacetic acid (0.17 g, 0.348 mmol), 2-chloropyrazine (0.08 g, 0.70 mmol) and potassium carbonate (0.24 g, 1.74 mmol) in 1 ml DMF was stirred at 80 deg. After 18 h the mixture was diluted with EtOAc, washed with H₂O, dried (Na₂SO₄), concentrated and purified by prep HPLC (5-70% ACN/H₂O) afforded a clear foam (44 mg, 0.10 mmol, 29%). LCMS-ES (Pos) m/z: 438 [M+H]⁺. ¹H NMR (400 MHz, DMSO-d₆) δ 9.78 (s, 1H), 8.30 (d, J=1.4 Hz, 1H), 8.18-7.91 (m, 2H), 7.83 (d, J=2.6 Hz, 1H), 7.44 (m, 5H), 7.24 (d, J=8.3 Hz, 2H), 5.15 (s, 2H), 3.68-3.01 (m, 9H), 2.45 (m, 3H).

Method J. Synthesis of 4-chlorobenzyl (4-((1-carbamoylpiperidin-4-yl)methyl)phenyl)carbamate (Compound 62)

To a mixture of 4-chlorobenzyl (4-(piperidin-4-ylmethyl)phenyl)carbamate hydrochloride (79 mg, 0.20 mmol, 1.00 equiv), in DMF (1 mL) and H₂O (1 mL) was added potassium cyanate (49 mg, 0.60 mmol, 3.00 equiv). The reaction mixture was stirred at 60° C. for 16 h. H₂O (10 mL) was added to the mixture. The precipitate was filtered and washed with H₂O (5 mL), then dried over high vacuum to afford the desired product 4-chlorobenzyl (4-((1-carbamoylpiperidin-4-yl)methyl)phenyl)carbamate (55 mg, 68%) as a white solid. LRMS (ES) m/z: 402 [M+H]⁺. ¹H NMR (400 MHz, DMSO-d₆) δ 9.69 (s, 1H), 7.46 (s, 4H), 7.36 (d, J=8.0 Hz, 2H), 7.07 (d, J=8.1 Hz, 2H), 5.82 (s, 2H), 5.14 (s, 2H), 3.88 (d, J=13.1 Hz, 2H), 2.57 (d, J=12.5 Hz, 1H), 2.43 (d, J=7.0 Hz, 3H), 1.76-1.39 (m, 3H), 1.15-0.76 (m, 2H).

Method K. Synthesis of oxazol-5-ylmethyl (4-(2-(1-(oxetane-3-carbonyl)piperidin-4-yl)ethyl)phenyl)carbamate (Compound 13)

To a solution of oxetane-3-carboxylic acid (20 mg, 0.20 mmol, 2.00 equiv) in DMF (1 mL) was added HBTU (57 mg, 0.15 mmol, 1.50 equiv), DIEA (30 mg, 0.23 mmol, 2.30 equiv). The mixture was stirred for 10 min. oxazol-5-ylmethyl (4-(2-(piperidin-4-yl)ethyl)phenyl)carbamate hydrochloride (37 mg, 0.12 mmol, 1.0 equiv) was added. The reaction mixture was stirred for 30 min. The mixture was purified by Prep-HPLC with the following conditions (Column: XBridge Prep OBD C18 Column 30×150 mm 5 um; Mobile Phase A:Water (0.1% formic acid), Mobile Phase B: MeCN (0.1% formic acid; Flow rate: 20 mL/min) to afford the desired product oxazol-5-ylmethyl (4-(2-(1-(oxetane-3-carbonyl)piperidin-4-yl)ethyl)phenyl)carbamate as a white solid (20 mg, 48%). LRMS (ES) m/z: 414 [M+H]⁺. ¹H NMR (400 MHz, Methanol-d₄) δ 8.23 (s, 1H), 7.34 (d, J=8.1 Hz, 2H), 7.25 (s, 1H), 7.20-7.07 (m, 2H), 5.24 (s, 2H), 4.85-4.70 (m, 4H), 4.51 (ddt, J=13.2, 4.6, 2.5 Hz, 1H), 4.16 (h, J=7.7 Hz, 1H), 3.44 (ddt, J=13.6, 4.5, 2.4 Hz, 1H), 2.96 (ddd, J=13.6, 12.5, 2.8 Hz, 1H), 2.72-2.54 (m, 3H), 1.80 (ddt, J=13.2, 8.1, 2.2 Hz, 2H), 1.68-1.45 (m, 3H), 1.18-1.01 (m, 2H).

Compounds in the following table were prepared in a similar manner as above example compounds, using the intermediates with alkylation/acylation reagents and methods as listed.

		Alkylation/
		acylation
	Inter-	Reagent
Co#	mediate	Method	Structure, Name and Data
17	6.2	MeNHSO2Cl F
			Compound 17: 4-chlorobenzyl (4-((1-(N-
			methylsulfamoyl)piperidin-4-
			yl)methyl)phenyl)carbamate LRMS (ES) m/z: 452
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 7.46-7.32
			(m, 6H), 7.14-7.05 (m, 2H), 5.16 (s, 2H), 3.62 (dt, J = 12.1,
			2.6 Hz, 2H), 2.69 (td, J = 12.2, 2.4 Hz, 2H), 2.62 (s, 3H),
			2.52 (d, J = 6.9 Hz, 2H), 1.76-1.54 (m, 3H), 1.36-1.14
			(m, 2H).
102	6.2	c-BuCOCl C
			Compound 102: 4-chlorobenzyl (4-((1-
			(cyclobutanecarbonyl)piperidin-4-
			yl)methyl)phenyl)carbamate. LRMS (ES) m/z: 441
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 7.56-7.26
			(m, 6H), 7.10 (d, J = 8.1 Hz, 2H), 5.17 (s, 2H), 4.47 (d, J =
			13.3 Hz, 1H), 3.85-3.67 (m, 1H), 3.46-3.35 (m, 1H), 2.94
			(t, J = 12.4 Hz, 1H), 2.68-2.48 (m, 3H), 2.41-2.10 (m,
			4H), 2.10-1.91 (m, 1H), 1.91-1.56 (m, 4H), 1.16-1.03
			(m, 2H).
313	7.2	oxetan-3-one A
			Compound 313. 1,3-oxazol-5-ylmethyl N-{4-[1-(oxetan-
			3-yl)piperidin-4-yl]phenyl}carbamate. LCMS-ES (Pos)
			m/z: 358 [M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.73
			(s, 1H), 8.43 (s, 1H), 7.40-7.28 (m, 3H), 7.16 (d, J = 8.1
			Hz, 2H), 5.21 (s, 2H), 4.54 (t, J = 6.5 Hz, 2H), 4.44 (t, J =
			6.1 Hz, 2H), 3.39 (t, J = 6.4 Hz, 1H), 2.78 (d, J = 10.9 Hz,
			2H), 2.43 (t, J = 12.0 Hz, 1H), 1.83 (t, J = 11.3 Hz, 2H),
			1.76-1.67 (m, 1H), 1.70 (s, 1H), 1.63 (td, J = 11.9, 11.4,
			3.3 Hz, 2H).
15	7.2	Ac2O B
			Compound 15: (4-chlorophenyl)methyl N-[4-(1-
			acetylpiperidin-4-yl)phenyl]carbamate LCMS-APCI
			(POS.) m/z: 387.1 [M + H]+. 1H NMR (400 MHz, Methanol-
			d4) δ 7.44-7.25 (m, 6H), 7.14 (d, J = 8.3 Hz, 2H), 5.14 (s,
			2H), 4.68-4.60 (m, 1H), 3.98 (m, 1H), 3.21 (td, J = 13.2,
			2.6 Hz, 1H), 2.72 (m, 2H), 1.98-1.78 (m, 2H), 1.60 (m,
			2H).
198	7.2	oxetan-3-one A
			Compound 198: (4-chlorophenyl)methyl N-{4-[1-
			(oxetan-3-yl)piperidin-4-yl]phenyl}carbamate. LCMS-
			APCI (POS.) m/z: 447.1 [M + H]+. 1H NMR (400 MHz,
			DMSO-d6) δ 9.70 (s, 1H), 8.19 (s, 1H), 7.46 (s, 4H), 7.38
			(d, J = 8.2 Hz, 2H), 7.24-7.05 (m, 2H), 5.13 (s, 2H), 4.54
			(t, J = 6.5 Hz, 2H), 4.44 (t, J = 6.1 Hz, 2H), 3.39 (p, J = 6.4
			Hz, 1H), 2.78 (d, J = 10.9 Hz, 2H), 2.43 (ddt, J = 11.9, 7.7,
			3.9 Hz, 1H), 1.83 (td, J = 11.6, 2.4 Hz, 2H), 1.77-1.51 (m,
			4H).
31	8.2	MeCOCl C
			Compound 31: oxazol-5-ylmethyl (4-((1-
			acetylpiperidin-4-yl)methyl)phenyl)carbamate LRMS
			(ES) m/z: 359 [M + H]+. 1H NMR (400 MHz, Methanol-d4)
			δ 8.24 (s, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.25 (s, 1H), 7.11
			(d, J = 8.2 Hz, 2H), 5.25 (s, 2H), 4.49 (dq, J = 14.2, 2.6 Hz,
			1H), 3.94-3.78 (m, 1H), 3.10-2.94 (m, 1H), 2.66-2.42
			(m, 3H), 2.09 (s, 3H), 1.88-1.62 (m, 3H), 1.26-1.02 (m,
			2H)
35	8.2	i-PrCOCl C
			Compound 35: oxazol-5-ylmethyl (4-((1-
			isobutyrylpiperidin-4-yl)methyl)phenyl)carbamate
			LRMS (ES) m/z: 386 [M + H]+. 1H NMR (400 MHz,
			Methanol-d4) δ 8.23 (s, 1H), 7.36 (d, J = 8.1 Hz, 2H), 7.25
			(s, 1H), 7.10 (d, J = 8.2 Hz, 2H), 5.24 (s, 2H), 4.58-4.42
			(m, 1H), 4.10-3.90 (m, 1H), 3.10-2.99 (m, 1H), 2.93 (h,
			J = 6.8 Hz, 1H), 2.67-2.36 (m, 3H), 1.91-1.59 (m, 3H),
			1.29-0.92 (m, 9H).
30	8.2	Me2NCOCl G
			Compound 30: oxazol-5-ylmethyl (4-((1-
			(dimethylcarbamoyl)piperidin-4-
			yl)methyl)phenyl)carbamate LRMS (ES) m/z:
			387[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.24 (s,
			1H), 7.35 (d, J = 8.0 Hz, 2H), 7.25 (s, 1H), 7.18-6.98 (m,
			2H), 5.24 (s, 2H), 3.64 (d, J = 13.0 Hz, 2H), 2.82 (d, J = 1.4
			Hz, 6H), 2.72 (td, J = 12.8, 2.3 Hz, 2H), 2.52 (d, J = 6.9 Hz,
			2H), 1.76-1.56 (m, 3H), 1.28-1.12 (m, 2H).
11	8.2	MeOCOCl D
			Compound 11: methyl 4-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)piperidine-1-
			carboxylate LRMS (ES) m/z: 374 [M + H]+. 1H NMR
			(400 MHz, Methanol-d4) δ 8.24 (s, 1H), 7.35 (d, J = 8.0
			Hz, 2H), 7.25 (s, 1H), 7.10 (d, J = 8.2 Hz, 2H), 5.25 (s,
			2H), 4.08 (d, J = 13.1 Hz, 2H), 3.68 (s, 3H), 2.86-1.67
			(m, 2H), 2.52 (d, J = 7.0 Hz, 2H), 1.81-1.51 (m, 3H),
			1.22-1.05 (m, 2H).
18	8.2	MeSO2Cl E
			Compound 18: oxazol-5-ylmethyl (4-((1-
			(methylsulfonyl)piperidin-4-
			yl)methyl)phenyl)carbamate LRMS (ES) m/z: 394
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.24 (s, 1H),
			7.36 (d, J = 8.0 Hz, 2H), 7.25 (s, 1H), 7.11 (d, J = 8.1 Hz,
			2H), 5.24 (s, 2H), 3.69 (d, J = 11.2 Hz, 2H), 2.80 (s, 3H),
			2.66 (td, J = 12.1, 2.5 Hz, 2H), 2.54 (d, J = 7.1 Hz, 2H),
			1.84-1.52 (m, 3H), 1.38-1.20 (m, 2H).
10	8.2	MeNHSO2Cl F
			Compound 10: oxazol-5-ylmethyl (4-((1-(N-
			methylsulfamoyl)piperidin-4-
			yl)methyl)phenyl)carbamate. LRMS (ES) m/z: 409
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.23 (s, 1H),
			7.35 (d, J = 8.0 Hz, 2H), 7.25 (s, 1H), 7.10 (d, J = 8.2 Hz,
			2H), 5.24 (s, 2H), 3.62 (d, J = 12.3 Hz, 2H), 2.69 (td, J =
			12.2, 2.3 Hz, 2H), 2.62 (s, 3H), 2.52 (d, J = 6.9 Hz, 2H),
			1.74-1.50 (m, 3H), 1.35-1.19 (m, 2H).
27	8.2	Me2NSO2Cl F
			Compound 27: oxazol-5-ylmethyl (4-((1-(N,N-
			dimethylsulfamoyl)piperidin-4-
			yl)methyl)phenyl)carbamate LRMS (ES) m/z: 409
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.23 (s, 1H),
			7.35 (d, J = 8.0 Hz, 2H), 7.25 (s, 1H), 7.14-6.96 (m, 2H),
			5.24 (s, 2H), 3.64 (dq, J = 12.5, 2.4 Hz, 2H), 2.79 (s,
			6H),2.80-2.69 (m, 2H), 2.52 (d, J = 6.7 Hz, 2H), 1.77-
			1.47 (m, 3H), 1.42-1.04 (m, 2H).
80	8.2	oxetan-3-one A
			Compound 80: oxazol-5-ylmethyl (4-((1-(oxetan-3-
			yl)piperidin-4-yl)methyl)phenyl)carbamate LRMS (ES)
			m/z: 372 [M + H]+. 1H NMR (400 MHz, Methanol-d4) δ
			8.36 (s, 1H), 8.24 (s, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.25 (s,
			1H), 7.16-7.02 (m, 2H), 5.25 (s 2H), 4.75 (t, J = 7.1 Hz,
			2H), 4.69 (t, J = 6.7 Hz, 2H), 3.86 (p, J = 6.7 Hz, 1H),
			3.07 (d, J = 11.8 Hz, 2H), 2.56 (d, J = 6.9 Hz, 2H), 2.26 (t,
			J = 12.0 Hz, 2H), 1.86-1.60 (m, 2H), 1.50-1.26 (m, 2H).
48	8.2	oxetane-3- carbonyl chloride C
			Compound 48: oxazol-5-ylmethyl (4-((1-(oxetane-3-
			carbonyl)piperidin-4-yl)methyl)phenyl)carbamate
			LRMS (ES) m/z: 400 [M + H]+. 1H NMR (400 MHz,
			Methanol-d4) δ 8.24 (s, 1H), 7.35 (d, J = 7.9 Hz, 2H), 7.25
			(s, 1H), 7.17-7.00 (m, 2H), 5.24 (s, 2H), 4.86-4.73 (m,
			4H), 4.49 (dq, J = 13.0, 2.2 Hz, 1H), 4.15 (p, J = 7.8 Hz,
			1H), 3.47-3.36 (m, 1H), 2.93 (td, J = 13.1, 2.5 Hz, 1H),
			2.61 (td, J = 12.9, 2.7 Hz, 1H), 2.55-2.34 (m, 2H), 1.90-
			1.55 (m, 3H), 1.20-0.99 (m, 2H).
293	8.2	MeOCH2CH2Br H
			Compound 293: oxazol-5-ylmethyl (4-((1-(2-
			methoxyethyl)piperidin-4-yl)methyl)phenyl)carbamate
			LRMS (ES) m/z: 374 [M + H]+. 1H NMR (400 MHz,
			Methanol-d4) δ 8.24 (d, J = 2.2 Hz, 1H), 7.37 (d, J = 8.0 Hz,
			2H), 7.25 (s, 1H), 7.12 (d, J = 8.0 Hz, 2H), 5.25 (s, 2H),
			3.67 (s, 2H), 3.51-3.38 (m, 2H), 3.40 (s, 3H), 3.15 (t, J =
			5.2 Hz, 2H), 2.78 (t, J = 12.5 Hz, 2H), 2.57 (d, J = 6.4 Hz,
			2H), 1.88-1.73 (m, 3H), 1.58-1.41 (m, 2H).
70	8.2	F2CHCH2OTf H
			Compound 70: oxazol-5-ylmethyl (4-((1-(2,2,2-
			trifluoroethyl)piperidin-4-yl)methyl)phenyl)carbamate
			LRMS (ES) m/z: 398 [M + H]+. 1H NMR (400 MHz,
			Methanol-d4) δ 8.24(s, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.25
			(d, J = 2.2 Hz, 1H), 7.18-6.98 (m, 2H), 5.24 (s, 2H), 3.10-
			2.90 (m, 4H), 2.50 (dd, J = 7.0, 2.2 Hz, 2H), 2.29 (t, J =
			11.7 Hz, 2H), 1.68-1.40 (m, 3H), 1.38-1.22 (m, 2H).
115	10.2	MeOCOCl D
			Compound 115: pyridin-4-ylmethyl (4-((1-
			acetylpiperidin-4-yl)methyl)phenyl)carbamate. LCMS-
			ES (Pos) m/z: 368.1 [M + H]+. 1H NMR (400 MHz, DMSO-
			d6) δ 9.80 (s, 1H), 8.58 (d, J = 4.9 Hz, 2H), 7.41-7.34 (m,
			4H), 7.08 (d, J = 7.9 Hz, 2H), 5.19 (s, 2H), 4.32 (d, J = 13.2
			Hz, 1H), 3.75 (d, J = 13.6 Hz, 1H), 3.22-3.12 (m, 1H),
			2.92 (t, J = 12.9 Hz, 1H), 2.44 (d, J = 8.0 Hz, 2H), 1.95 (s,
			3H), 1.75-1.63 (m, 1H), 1.55 (t, J = 13.0 Hz, 2H), 1.14-
			1.00 (m, 1H), 1.00-0.88 (m, 1H).
23	10.2	MeOCOCl D
			Compound 23: methyl 4-(4-(((pyridin-4-
			ylmethoxy)carbonyl)amino)benzyl)piperidine-1-
			carboxylate. LCMS-ES (Pos) m/z: 384.1 [M + H]+. 1H
			NMR (400 MHz, Methanol-d4) δ 8.53 (d, J = 3.4 Hz 2H),
			7.47 (d, J = 5.0 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 7.09 (d,
			J = 8.5, Hz, 2H), 5.25 (s, 2H), 4.06 (d, J = 13.2 Hz, 2H),
			3.66 (s, 3H), 2.83-2.65 (m, 2H), 2.50 (d, J = 7.1 Hz, 2H),
			1.79-1.55 (m, 3H), 1.11 (qd, J = 12.3, 6.7 Hz, 2H).
316	10.2	3-oxetanone A
			Compound 316: 1,3-oxazol-5-ylmethyl N-[4-(piperidin-
			4-yl)phenyl]carbamate.
			LCMS-ES (Pos) m/z: 382 [M + H]+. 1H NMR (400 MHz,
			DMSO-d6) δ 9.80 (s, 1H), 8.58 (d, J = 4.9 Hz, 2H), 8.15
			(s, 1H), 7.42-7.33 (m, 4H), 7.07 (d, J = 8.4 Hz, 2H), 5.20
			(s, 2H), 4.49 (t, J = 6.7 Hz, 2H), 4.38 (t, J = 5.9 Hz, 2H),
			3.70 (d, J = 9.5 Hz, 1H), 3.49 (d, J = 12.2 Hz, 1H), 2.64
			(d, J = 11.1 Hz, 2H), 2.44 (d, J = 6.7 Hz, 1H), 1.65 (t, J =
			11.4 Hz, 2H), 1.53 (d, J = 12.9 Hz, 2H), 1.18 (t, J = 11.4
			Hz, 2H).
52	10.2	F2CHCH2OTf H
			Compound 52: 1,3-oxazol-5-ylmethyl N-[4-(piperidin-
			4-yl)phenyl]carbamate. LCMS-ES (Pos) m/z: 390
			[M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 12.68 (s, 1H),
			9.72 (s, 1H), 8.42 (d, J = 2.0 Hz, 1H), 8.14 (d, J = 2.0 Hz,
			1H), 7.33 (dd, J = 22.8, 5.0 Hz, 3H), 7.22-7.03 (m, 2H),
			6.16 (s, 1H), 5.21 (s, 2H), 4.10 (s, 1H), 3.18 (s, 1H), 3.00
			(d, J = 11.1 Hz, 2H), 2.91-2.63 (m, 2H), 2.42 (t, J = 12.1
			Hz, 1H), 2.26 (t, J = 11.5 Hz, 2H), 1.96-1.52 (m, 4H).
7	9.2	i-PrCOCl C
			Compound 7: 1,3-oxazol-5-ylmethyl N-{4-[1-(2-
			methylpropanoyl)piperidin-4-yl]phenyl}carbamate.
			LCMS-ES (Pos) m/z: 372.1 [M + H]+. 1H NMR (400 MHz,
			DMSO-d6) δ 9.73 (s, 1H), 8.42 (d, J = 2.0 Hz, 1H), 7.49-
			7.26 (m, 2H), 7.16 (d, J = 8.1 Hz, 2H), 5.21 (s, 2H), 4.55 (d,
			J = 12.8 Hz, 1H), 4.16-3.91 (m, 1H), 3.09 (t, J = 13.0 Hz,
			1H), 2.90 (p, J = 6.8 Hz, 1H), 2.71 (t, J = 12.3 Hz, 1H), 2.58
			(d, J = 12.0 Hz, 2H), 1.78 (s, 2H), 1.60-1.25 (m, 2H), 1.25-
			0.89 (m, 6H).
8	9.2	Ac2O B
			Compound 8: 1,3-oxazol-5-ylmethyl N-[4-(1-
			acetylpiperidin-4-yl)phenyl]carbamate
			LCMS-ES (Pos) m/z: 344 [M + H]+. 1H NMR (400 MHz,
			DMSO-d6) δ 9.74 (s, 1H), 7.49-7.22 (m, 3H), 7.16 (d, J =
			8.1 Hz, 2H), 5.21 (s, 2H), 4.64-4.39 (m, 1H), 3.90 (d, J =
			13.6 Hz, 1H), 3.10 (t, J = 12.9 Hz, 1H), 2.69 (t, J = 12.2 Hz,
			1H), 2.57 (d, J = 13.0 Hz, 2H), 2.02 (s, 3H), 1.74 (t, J = 13.8
			Hz, 2H), 1.47 (dtt, J = 57.2, 12.5, 6.3 Hz, 2H).
88	9.2	F3CCH2OTf H
			Compound 88: 1,3-oxazol-5-ylmethyl N-{4-[1-(2,2,2-
			trifluoroethyl)piperidin-4-yl]phenyl}. LCMS-ES (Pos)
			m/z: 384 [M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.73
			(s, 1H), 8.42 (d, J = 2.0 Hz, 1H), 7.33 (dd, J = 23.5, 5.0 Hz,
			3H), 7.21-6.90 (m, 2H), 5.21 (s, 2H), 3.11 (d, J = 74.1 Hz,
			2H), 3.38 (m, 2H), 2.44 (s, 2H), 1.67 (d, J = 15.8 Hz, 4H).
113	9.2	F2CHCH2OTf H
			Compound 113: 1,3-oxazol-5-ylmethyl N-{4-[1-(2,2-
			difluoroethyl)piperidin-4-yl]phenyl}carbamate. LCMS-
			ES (Pos) m/z: 366 [M + H]+. 1H NMR (400 MHz, DMSO-
			d6) δ 9.72 (s, 1H), 8.42 (d, J = 2.0 Hz, 1H), 8.14 (d, J = 2.0
			Hz, 1H), 7.33 (dd, J = 22.8, 5.0 Hz, 3H), 7.22-7.03 (m,
			2H), 6.16 (s, 1H), 5.21 (s, 2H), 4.10 (s, 1H), 3.18 (s, 1H),
			3.00 (d, J = 11.1 Hz, 2H), 2.91-2.63 (m, 1H), 2.42 (t, J =
			12.1 Hz, 1H), 2.26 (t, J = 11.5 Hz, 2H), 1.96-1.52 (m, 2H).
148	9.2	MeOCOCl D
			Compound 148. methyl 4-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)phenyl)piperidine-1-
			carboxylate LCMS-ES (Pos) m/z: 360 (M + H). 1H NMR
			(400 MHz, DMSO-d6) δ 9.74 (s, 1H), 8.43 (s, 1H), 7.43-
			7.26 (m, 2H), 7.16 (d, J = 8.1 Hz, 2H), 5.21 (s, 2H), 4.09 (s,
			2H), 3.61 (s, 3H), 2.86 (m, 3H), 2.64 (t, J = 12.3 Hz, 1H),
			1.72 (d, J = 12.9 Hz, 2H), 1.47 (qd, J = 12.7, 4.2 Hz, 2H).
4	9.2	Me2NCOCl G
			Compound 4: oxazol-5-ylmethyl (4-(1-
			(dimethylcarbamoyl)piperidin-4-yl)phenyl)carbamate.
			LCMS-ES (Pos) m/z: 373 [M + H]+. 1H NMR (400 MHz,
			DMSO-d6) δ 9.73 (s, 1H), 8.42 (s, 1H), 7.36 (d, J = 8.1 Hz,
			2H), 7.30 (s, 1H), 7.15 (d, J = 8.1 Hz, 2H), 5.20 (s, 2H),
			3.63 (d, J = 12.7 Hz, 2H), 2.80-2.70 (m, 2H), 2.74 (s, 6H),
			2.59 (t, J = 12.1 Hz, 1H), 1.75-1.67 (m, 2H), 1.54 (qd, J =
			12.5, 3.5 Hz, 2H).
348	9.2	MeOCH2CH2Br H
			Compound 348: 1,3-oxazol-5-ylmethyl N-{4-[1-(2-
			methoxyethyl)piperidin-4-yl]phenyl}carbamate.
			LCMS-ES (Pos) m/z: 360 [M + H]+. 1H NMR (400 MHz,
			DMSO-d6) δ 9.74 (s, 1H), 8.43 (s, 1H), 7.37 (d, J = 8.1 Hz,
			2H), 7.31 (s, 1H), 7.16 (d, J = 8.1 Hz, 2H), 5.21 (s, 2H),
			3.64 (d, J = 12.7 Hz, 2H), 2.75 (s, 8H), 2.60 (t, J = 12.1 Hz,
			1H), 1.72 (d, J = 12.2 Hz, 2H), 1.55 (m, 2H).
26	11.2	Ac2O B
			Compound 26: oxazol-5-ylmethyl (4-(2-(1-
			acetylpiperidin-4-yl)ethyl)phenyl)carbamate LRMS
			(ES) m/z: 372 [M + H]+. 1H NMR (400 MHz, Methanol-d4)
			δ 8.24 (s, 1H), 7.34 (d, J = 8.2 Hz, 2H), 7.25 (s, 1H), 7.20-
			7.01 (m, 2H), 5.24 (s, 2H), 4.50 (ddt, J = 13.1, 4.5, 2.5
			Hz, 1H), 3.91 (ddt, J = 13.5, 4.5, 2.4 Hz, 1H), 3.17-3.00
			(m, 1H), 2.67-2.53 (m, 3H), 2.10 (s, 3H), 1.91-1.75 (m,
			2H), 1.66-1.47 (m, 3H), 1.30-0.99 (m, 2H).
32	11.2	Me2NCOCl G
			Compound 32: oxazol-5-ylmethyl (4-(2-(1-
			(dimethylcarbamoyl)piperidin-4-
			yl)ethyl)phenyl)carbamate LRMS (ES) m/z: 372
			[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.24 (s,
			1H), 7.34 (d, J = 8.1 Hz, 2H), 7.25 (s, 1H), 7.18-7.02 (m,
			2H), 5.34-5.12 (m, 2H), 3.66 (dt, J = 13.0, 2.5 Hz, 2H),
			2.83 (s, 6H), 2.75 (td, J = 12.8, 2.5 Hz, 2H), 2.67-2.51
			(m, 2H), 1.83-1.69 (m, 2H), 1.69-1.52 (m, 2H), 1.52-
			1.40 (m, 1H), 1.31-1.09 (m, 2H).
120	11.2	MeOCOCl D
			Compound 120: methyl 4-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)phenethyl)piperidine-1-
			carboxylate LRMS (ES) m/z: 388 [M + H]+. 1H NMR (400
			MHz, Methanol-d4) δ 8.24 (s, 1H), 7.34 (d, J = 8.1 Hz, 2H),
			7.25 (s, 1H), 7.20-6.98 (m, 2H), 5.23 (s, 2H), 4.10 (d, J =
			13.3 Hz, 2H), 3.68 (s, 3H), 2.86-2.68 (m, 2H), 2.62 (dd,
			J = 9.0, 6.6 Hz, 2H), 1.84-1.70 (m, 2H), 1.64-1.38 (m,
			3H), 1.20-1.05 (m, 2H).
132	11.2	oxetan-3-one A
			Compound 132: oxazol-5-ylmethyl (4-(2-(1-(oxetan-3-
			yl)piperidin-4-yl)ethyl)phenyl)carbamate: LRMS (ES)
			m/z: 386 [M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 8.24
			(s, 1H), 7.34 (d, J = 8.2 Hz, 2H), 7.25 (s, 1H), 7.20-7.03
			(m, 2H), 5.25 (s, 2H), 4.73 (t, J = 7.0 Hz, 2H), 4.66 (t, J =
			6.5 Hz, 2H), 3.80-3.63 (m, 1H), 2.97 (d, J = 11.7 Hz, 2H),
			2.67-2.54 (m, 2H), 2.19-2.04 (m, 2H), 1.92-1.78 (m,
			2H), 1.66-1.52 (m, 2H), 1.46-1.30 (m, 3H).
223	25.2	oxetan-3-one A
			Compound 223: (4-chlorophenyl)methyl N-(4-{[4-
			(oxetan-3-yl)piperazin-1-yl]methyl}phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 416.0 [M + H]+. 1H NMR (400
			MHz, DMSO-d6) δ 9.76 (s, 1H), 7.42 (d, J = 28.2 Hz, 6H),
			7.18 (d, J = 8.4 Hz, 2H), 5.13 (s, 2H), 4.45 (dt, J = 43.6, 6.3
			Hz, 4H), 3.36 (d, J = 14.6 Hz, 4H), 2.24 (s, 7H).
318	26.2	oxetan-3-one A
			Compound 318: (4-methoxyphenyl)methyl N-(4-{[4-
			(oxetan-3-yl)piperazin-1-yl]methyl}phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 412.0 [M + H]+. 1H NMR (300
			MHz, DMSO-d6) δ 9.66 (s, 1H), 7.37 (t, J = 8.4 Hz, 4H),
			7.17 (d, J = 8.4 Hz, 2H), 6.94 (d, J = 8.6 Hz, 2H), 5.06 (s,
			2H), 4.45 (dt, J = 32.7, 6.3 Hz, 4H), 3.75 (s, 3H), 2.33 (d,
			J = 10.8 Hz, 9H).
29	25.2	2- chloropyridine I
			Compound 29: (4-chlorophenyl)methyl N-(4-{[4-
			(pyridin-2-yl)piperazin-1-yl]methyl}phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 437.0 [M + H]+. 1H NMR (300
			MHz, DMSO-d6) δ 9.77 (s, 1H), 8.09 (dd, J = 5.0, 1.9 Hz,
			1H), 7.54-7.38 (m, 7H), 7.23 (d, J = 8.3 Hz, 2H), 6.79 (d,
			J = 8.6 Hz, 1H), 6.62 (dd, J = 7.0, 4.9 Hz, 1H), 5.14 (s, 2H),
			3.44 (d, J = 5.2 Hz, 6H), 2.42 (t, J = 5.1 Hz, 4H).
83	26.2	2- chloropyridine
			Compound 83: (4-methoxyphenyl)methyl N-(4-{[4-
			(pyridin-2-yl)piperazin-1-yl]methyl}phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 433.0 [M + H]+. 1H NMR (400
			MHz, DMSO-d6) δ 9.69 (s, 1H), 8.09 (dd, J = 5.1, 1.9 Hz,
			1H), 7.55-7.46 (m, 1H), 7.41 (d, J = 8.0 Hz, 2H), 7.37 (d,
			J = 8.2 Hz, 2H), 7.22 (d, J = 8.1 Hz, 2H), 6.95 (d, J = 8.2
			Hz, 2H), 6.79 (d, J = 8.6 Hz, 1H), 6.62 (dd, J = 7.2, 4.9 Hz,
			1H), 5.07 (s, 2H), 3.75 (s, 3H), 3.48-3.40 (m, 6H), 2.42 (d,
			J = 5.1 Hz, 4H).
73	25.2	2-chloro- pyrimidine I
			Compound 73: 4-chlorobenzyl (4-((4-(pyrimidin-2-
			yl)piperazin-1-yl)
			methyl)phenyl)carbamate. LCMS-ES (Pos) m/z: 438
			[M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			8.33 (d, J = 4.7 Hz, 2H), 7.49-7.44 (m, 4H), 7.42 (d, J =
			8.2 Hz, 2H), 7.22 (d, J = 8.5 Hz, 2H), 6.60 (t, J = 4.7 Hz,
			1H), 5.14 (s, 2H), 3.73-3.67 (m, 4H), 3.43 (s, 2H), 2.41-
			2.35 (m, 4H).
107	25.2	MeSO2Cl E
			Compound 107: (4-chlorophenyl)methyl N-{4-[(4-
			methanesulfonylpiperazin-1-
			yl)methyl]phenyl}carbamate
			LCMS-ES (Pos) m/z: 438 [M + H]+. 1H NMR (400 MHz,
			DMSO-d6) δ 9.78 (s, 1H), 7.50-7.37 (m, 6H), 7.29-7.15
			(m, 2H), 5.14 (s, 2H), 3.51-3.39 (m, 2H), 3.14-3.04 (m,
			4H), 2.95-2.81 (m, 4H), 2.42 (bs, 3H).
177	25.2	2,2- dimethyl- oxirane I
			Compound 177: 4-chlorobenzyl (4-((4-(2-hydroxy-2-
			methylpropyl)piperazin-1-yl)methyl)phenyl)carbamate
			LCMS-ES (Pos) m/z: 432 [M + H]+. 1H NMR (400 MHz,
			DMSO-d6) δ 9.75 (s, 1H), 8.15 (s, 1H), 7.49-7.42 (m, 4H),
			7.42-7.35 (m, 2H), 7.22-7.15 (m, 2H), 5.13 (s, 2H), 3.42
			(s, 1H), 3.38 (s, 2H), 3.34 (dd, J = 10.0, 5.1 Hz, 1H), 2.57-
			2.48 (m, 3H), 2.42-2.23 (m, 4H), 2.18 (s, 1H), 1.06 (s,
			6H).
191	25.2	Ac2O B
			Compound 191: (4-chlorophenyl)methyl N-{4-[(4-
			acetylpiperazin-1-yl)methyl]phenyl}carbamate.
			LCMS-ES (Pos) m/z: 402 [M + H]+. 1H NMR (400 MHz,
			DMSO-d6) δ 9.85 (s, 1H), 7.55-7.39 (m, 6H), 7.33-7.18
			(m, 2H), 5.14 (s, 2H), 3.86-3.09 (m, 9H), 2.45-2.22 (m,
			1H), 1.98 (s, 3H).
269	oxazol- 5- ylmethyl (4-(2- (piperazin- 1- yl)ethyl) phenyl) carbamate	oxetan-3-one A
			Compound 269: 1,3-oxazol-5-ylmethyl N-(4-{2-[4-
			(oxetan-3-yl)piperazin-1-yl]ethyl}phenyl)carbamate.
			LCMS-ES (Pos) m/z: 387 [M + H]+. 1H NMR (400 MHz,
			DMSO-d6) δ 9.71 (s, 1H), 8.41 (s, 1H), 7.34 (d, J = 8.0
			Hz, 2H), 7.30 (s, 1H), 7.12 (d, J = 8.0 Hz, 2H), 5.20 (s,
			2H), 4.51 (t, J = 6.5 Hz, 2H), 4.41 (t, J = 6.1 Hz, 2H), 3.44-
			3.34 (m, 3H), 2.69-2.62 (m, 2H), 2.55-2.40 (m, 4H),
			2.35-2.15 (m, 4H).
232	13.2	oxetan-3-one A
			Compound 232: 4-chlorobenzyl (4-(((1-(oxetan-3-
			yl)piperidin-4-yl)oxy)methyl)phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 431.1 [M + H]+. 1H NMR (400
			MHz, Methanol-d4) δ 8.44 (s, 1H), 7.30 (p, J = 8.1 Hz, 6H),
			7.18 (t, J = 9.3 Hz, 2H), 5.06 (s, 2H), 4.57 (t, J = 6.8 Hz,
			1H), 4.49 (d, J = 6.5 Hz, 1H), 4.43 (s, 1H), 4.39 (s, 1H),
			3.66 (s, 1H), 2.99 (dd, J = 12.3, 5.9 Hz, 2H), 2.52 (s, 1H),
			2.03-1.74 (m, 5H), 1.58 (s, 1H), 1.19 (s, 1H).
93	13.2	Ac2O B
			Compound 93: 4-chlorobenzyl (4-(((1-acetylpiperidin-4-
			yl)oxy)methyl)phenyl)carbamate.
			(LCMS-APCI (POS.) m/z: 417.1 [M + H]+. 1H NMR (400
			MHz, Methanol-d4) δ 7.44-7.35 (m, 6H), 7.28 (d, J = 8.2
			Hz, 2H), 5.16 (s, 2H), 4.52 (s, 2H), 3.93-3.85 (m, 1H),
			3.77-3.64 (m, 2H), 2.09 (s, 3H), 2.07-1.99 (m, 2H), 1.97-
			1.83 (m, 2H), 1.66-1.50 (m, 2H).
354	14.2	oxetan-3-one A
			Compound 354: 4-chlorobenzyl (4-(((1-(oxetan-3-
			yl)azetidin-3-yl)oxy)methyl)phenyl)carbamate.
			(LCMS-APCI (POS.) m/z: 403.1 [M + H]+. 1H NMR (400
			MHz, Methanol-d4) δ 7.36-7.25 (m, 6H), 7.17 (d, J = 8.5
			Hz, 2H), 5.06 (s, 2H), 4.62 (t, J = 6.8 Hz, 2H), 4.35 (dd, J =
			7.0, 4.9 Hz, 2H), 4.32 (s, 2H), 4.17 (p, J = 5.9 Hz, 1H), 3.73
			(ddd, J = 11.5, 6.6, 5.0 Hz, 1H), 3.53 (td, J = 6.5, 1.9 Hz,
			2H), 3.09-3.03 (m, 2H).
16	14.2	Ac2O B
			Compound 16: 4-chlorobenzyl (4-(((1-acetylazetidin-3-
			yl)oxy)methyl)phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 389.1 [M + H]+. 1H NMR (400
			MHz, Methanol-d4) δ 7.47-7.34 (m, 6H), 7.31-7.25 (m,
			2H), 5.16 (s, 2H), 4.59-4.52 (m, 1H), 4.45 (s, 1H), 4.42-
			4.36 (m, 1H), 4.35-4.28 (m, 1H), 4.10 (dd, J = 10.7, 6.6
			Hz, 1H), 4.02 (dd, J = 9.6, 3.8 Hz, 1H), 3.77 (dd, J = 10.9,
			4.0 Hz, 1H), 1.85 (s, 3H).
357	31.1	isobutyryl chloride
			Compound 357: oxazol-5-ylmethyl (4-(2-isobutyryl-2-
			azaspiro[3.3]heptan-6-yl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 384.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H), 8.41 (s,
			1H), 7.36 (d, J = 8.2 Hz, 2H), 7.30 (s, 1H), 7.13 (d, J = 8.4
			Hz, 2H), 5.20 (s, 2H), 4.26 (s, 1H), 4.05 (s, 1H), 3.94 (s,
			1H), 3.73 (s, 1H), 2.67 (s, 1H), 2.25-2.16 (m, 3H), 1.72
			(s, 1H), 1.50 (s, 1H), 0.95 (t, J = 6.7 Hz, 6H).
358	31.1	acetic anhydride
			Compound 358: oxazol-5-ylmethyl (4-(2-acetyl-2-
			azaspiro[3.3]heptan-6-yl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 356.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.70 (s, 1H), 8.39 (s,
			1H), 7.34 (d, J = 8.2 Hz, 2H), 7.27 (s, 1H), 7.11 (d, J = 8.6
			Hz, 2H), 5.18 (s, 3H), 4.20 (s, 1H), 3.98 (s, 1H), 3.91 (s,
			1H), 3.70 (s, 1H), 2.18 (ddd, J = 12.0, 9.5, 2.4 Hz, 3H),
			1.71 (d, J = 10.3 Hz, 4H).
359	30.1	methane- sulfonyl chloride
			Compound 359
			diastereoisomer 1 obtained after separation
			LCMS-ESI (POS.) m/z: 424.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.42 (s,
			1H), 7.31 (d, J = 1.8 Hz, 1H), 7.30-7.24 (m, 2H), 7.18
			(dd, J = 8.5, 2.1 Hz, 1H), 5.22 (s, 2H), 3.59 (p, J = 9.1 Hz,
			1H), 3.29 (t, J = 6.8 Hz, 2H), 3.17 (s, 2H), 2.86 (s, 3H),
			2.26 (td, J = 8.9, 2.0, 2H), 2.17 (td, J = 9.6, 2.5 Hz, 2H),
			2.06 (t, J = 6.7 Hz, 2H).
360	30.1	methane- sulfonyl chloride
			Compound 360
			diastereoisomer 2 obtained after separation
			LCMS-ESI (POS.) m/z: 424.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.42 (s,
			1H), 7.31 (s, 1H), 7.30-7.23 (m, 2H), 7.18 (dd, J = 8.3,
			2.1 Hz, 1H), 5.22 (s, 2H), 3.61 (p, J = 9.1 Hz, 1H), 3.39 (s,
			2H), 3.21 (t, J = 6.9 Hz, 2H), 2.91 (s, 3H), 2.36 (td, J =
			8.9, 2.4 Hz, 2H), 2.11 (td, J = 9.6, 2.7 Hz, 2H), 1.87 (t, J =
			7.0 Hz, 2H).
361	30.1	isobutyryl chloride
			Compound 361
			diastereoisomer 1 obtained after separation
			LCMS-ESI (POS.) m/z: 416.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.42 (s,
			1H), 7.31 (s, 1H), 7.30-7.24 (m, 2H), 7.21-7.14 (m,
			1H), 5.22 (s, 2H), 3.67-3.56 (m, 1H), 3.53 (t, J = 6.8 Hz,
			1H), 3.41 (s, 1H), 3.35-3.30 (m, 1H), 3.22 (s, 1H), 2.68-
			2.54 (m, 1H), 2.25 (dd, J = 8.6, 2.1 Hz, 2H), 2.20-2.10
			(m, 2H), 2.08 (t, J = 6.9 Hz, 1H), 1.98 (t, J = 6.9 Hz, 1H),
			0.98 (d, J = 2.3 Hz, 3H), 0.97 (d, J = 2.3 Hz, 3H).
362	30.1	isobutyryl chloride
			Compound 362
			diastereoisomer 2 obtained after separation
			LCMS-ESI (POS.) m/z: 416.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.42 (s,
			1H), 7.31 (s, 1H), 7.30-7.23 (m, 2H), 7.18 (dt, J = 8.4,
			1.7 Hz, 1H), 5.22 (s, 2H), 3.70-3.54 (m, 2H), 3.48-3.41
			(m, 2H), 3.25 (t, J = 7.1 Hz, 1H), 2.74-2.61 (m, 1H),
			2.34-2.25 (m, 2H), 2.13-2.06 (m, 2H), 1.88 (t, J = 7.0
			Hz, 1H), 1.78 (t, J = 7.1 Hz, 1H), 1.01 (d, J = 6.7 Hz, 3H),
			0.99 (d, J = 6.7 Hz, 3H).
363	30.1	dimethyl- carbamyl chloride
			Compound 363
			diastereoisomer 1 obtained after separation
			LCMS-ESI (POS.) m/z: 417.1 [M + H]+. 1H NMR (400
			MHz, DMSO-d6) δ 9.96 (s, 1H), 8.42 (s, 1H), 7.31 (s, 1H),
			7.30-7.24 (m, 2H), 7.17 (dd, J = 8.5, 2.1 Hz, 1H), 5.22
			(s, 2H), 3.58 (p, J = 9.1 Hz, 1H), 3.33-3.28 (m, 2H), 3.19
			(s, 2H), 2.71 (s, 6H), 2.23 (td, J = 8.7, 2.7 Hz, 2H), 2.09
			(td, J = 9.5, 2.6 Hz, 2H), 1.94 (t, J = 6.7 Hz, 2H).
364	30.1	dimethyl- carbamyl chloride
			Compound 364
			diastereoisomer 2 obtained after separation
			LCMS-ESI (POS.) m/z: 417.1 [M + H]+. 1H NMR (400
			MHz, DMSO-d6) δ 9.96 (s, 1H), 8.42 (s, 1H), 7.31 (s, 1H),
			7.30-7.21 (m, 2H), 7.17 (dd, J = 8.5, 2.1 Hz, 1H), 5.22
			(s, 2H), 3.59 (p, J = 9.1 Hz, 1H), 3.41 (s, 1H), 3.33-3.29
			(m, 1H), 3.24 (t, J = 6.9 Hz, 2H), 2.74 (s, 6H), 2.26
			(td, J = 9.0, 2.4 Hz, 2H), 2.07 (td, J = 9.6, 2.7 Hz, 2H),
			1.75 (t, J = 6.9 Hz, 2H).
372	30.1	acetic anhydride
			Compound 372
			diastereoisomer 1 obtained after separation
			LCMS-ESI (POS.) m/z: 388.1 [M + H]+. 1H NMR (400
			MHz, DMSO-d6) δ 9.96 (s, 1H), 8.42 (s, 1H), 7.31 (s, 1H),
			7.30-7.24 (m, 2H), 7.18 (ddd, J = 8.2, 5.1, 2.0 Hz, 1H),
			5.22 (s, 2H), 3.65-3.54 (m, 1H), 3.47 (t, J = 6.8 Hz, 1H),
			3.36 (s, 1H), 3.34-3.29 (m, 1H), 3.21 (s, 1H), 2.25
			(td, J = 10.0, 8.8, 2.1 Hz, 2H), 2.19-2.03 (m, 3H), 1.98
			(t, J = 7.0 Hz, 1H), 1.92-1.87 (m, 3H).
373	30.1	acetic anhydride
			Compound 373
			diastereoisomer 2 obtained after separation
			LCMS-ESI (POS.) m/z: 388.1 [M + H]+. 1H NMR (400
			MHz, DMSO-d6) δ 9.97 (s, 1H), 8.43 (s, 1H), 7.32 (s, 1H),
			7.31-7.24 (m, 2H), 7.19 (dt, J = 8.6, 2.0 Hz, 1H), 5.23 (s,
			2H), 3.68-3.54 (m, 2H), 3.45 (s, 1H), 3.40 (t, J = 7.0 Hz,
			1H), 3.25 (t, J = 7.1 Hz, 1H), 2.35-2.22 (m, 2H), 2.16-
			2.07 (m, 2H), 1.98-1.92 (m, 3H), 1.88 (t, J = 7.0 Hz,
			1H), 1.79 (t, J = 7.1 Hz, 1H).
375	30.2	acetic anhydride
			Compound 375: oxazol-5-ylmethyl (R)-(4-(1-
			acetylpiperidin-3-yl)phenyl)carbamate LCMS-ESI
			(POS.) m/z: 344.1 [M + H]+. 1H NMR (400 MHz, DMSO-
			d6) δ 9.76 (s, 1H), 8.43 (s, 1H), 7.44-7.34 (m, 2H), 7.31
			(s, 1H), 7.26-7.13 (m, 2H), 5.22 (s, 2H), 4.41 (dd, J =
			20.2, 12.0 Hz, 1H), 3.79 (dd, J = 30.9, 14.0 Hz, 1H), 3.18
			(d, J = 5.2 Hz, 1H), 3.11-2.99 (m, 1H), 2.02 (d, J = 5.6
			Hz, 3H), 1.88 (d, J = 12.4 Hz, 1H), 1.79-1.58 (m, 2H),
			1.57-1.29 (m, 2H).
365	30.2	methane- sulfonyl chloride
			Compound 365: oxazol-5-ylmethyl (R)-(4-(1-
			(methylsulfonyl)piperidin-3-yl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 380.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H), 8.42 (s,
			1H), 7.39 (d, J = 8.3 Hz, 2H), 7.30 (s, 1H), 7.26-7.18 (m,
			2H), 5.21 (s, 2H), 3.55 (dd, J = 22.8, 9.7 Hz, 2H), 2.87 (s,
			3H), 2.78-2.65 (m, 3H), 1.89-1.78 (m, 2H), 1.68-1.49
			(m, 2H).
366	30.2	dimethyl- sulfamoyl chloride
			Compound 366: oxazol-5-ylmethyl (R)-(4-(1-(N,N-
			dimethylsulfamoyl)piperidin-3-yl)phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 409.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H), 8.43 (s,
			1H), 7.39 (d, J = 8.2 Hz, 2H), 7.31 (s, 1H), 7.21 (d, J = 8.6
			Hz, 2H), 5.22 (s, 2H), 3.66-3.47 (m, 2H), 2.93-2.81 (m,
			2H), 2.75 (s, 6H), 2.68 (s, 1H), 1.91-1.73 (m, 2H), 1.63-
			1.51 (m, 2H).
368	378	isobutyryl chloride
			Compound 368: oxazol-5-ylmethyl (3-fluoro-4-((6-
			isobutyryl-6-azaspiro[3.4]octan-2-
			yl)methyl)phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 430.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.42 (s,
			1H), 7.34-7.27 (m, 2H), 7.20-7.10 (m, 2H), 5.23 (s,
			2H), 3.50-3.38 (m, 2H), 3.30-3.16 (m, 2H), 2.70-2.54
			(m, 3H), 2.04-1.88 (m, 3H), 1.86-1.63 (m, 4H), 0.97
			(dd, J = 6.7, 1.8 Hz, 6H).
379	378	dimethyl- carbamoyl chloride
			Compound 379: oxazol-5-ylmethyl (4-((6-
			(dimethylcarbamoyl)-6-azaspiro[3.4]octan-2-
			yl)methyl)-3-fluorophenyl)carbamate
			LCMS-ESI (POS.) m/z: 431.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.94 (s, 1H), 8.42 (s,
			1H), 7.35-7.23 (m, 2H), 7.21-7.06 (m, 2H), 5.22 (s,
			2H), 3.25-3.17 (m, 3H), 3.12 (s, 1H), 2.69 (s, 6H), 2.66-
			2.59 (m, 2H), 2.47-2.39 (m, 1H), 1.97-1.86 (m, 2H),
			1.76 (t, J = 6.7 Hz, 1H), 1.73-1.60 (m, 3H).
374	378	acetic anhydride
			Compound 374: oxazol-5-ylmethyl (4-((6-acetyl-6-
			azaspiro[3.4]octan-2-yl)methyl)-3-
			fluorophenyl)carbamate
			LCMS-ESI (POS.) m/z: 402.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.42 (s,
			1H), 7.33-7.27 (m, 2H), 7.18-7.10 (m, 2H), 5.22 (s,
			2H), 3.42-3.35 (m, 2H), 3.29 (s, 1H), 3.27-3.18 (m,
			2H), 3.16 (s, 1H), 2.68-2.61 (m, 3H), 1.91-1.97 (m,
			4H), 1.85-1.77 (m, 1H), 1.75-1.67 (m, 2H).
371	378	methyl carbono- chloridate
			Compound 371: methyl 2-(2-fluoro-4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)-6-
			azaspiro[3.4]octane-6-carboxylate
			LCMS-ESI (POS.) m/z: 418.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.93 (s, 1H), 8.41 (s,
			1H), 7.31-7.25 (m, 2H), 7.17-7.08 (m, 2H), 5.21 (s,
			2H), 3.54 (s, 3H), 3.27-3.18 (m, 4H), 3.14 (s, 2H), 1.99-
			1.89 (m, 2H), 1.86-1.79 (m, 2H), 1.75-1.64 (m, 3H).
367	378	propionyl chloride
			Compound 367: oxazol-5-ylmethyl (3-fluoro-4-((6-
			propionyl-6-azaspiro[3.4]octan-2-
			yl)methyl)phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 416.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.42 (s,
			1H), 7.33-7.27 (m, 2H), 7.20-7.08 (m, 2H), 5.23 (s,
			2H), 4.10 (q, J = 5.3 Hz, 2H), 3.18 (d, J = 5.3 Hz, 3H),
			2.35-2.31 (m, 1H), 2.18 (t, J = 7.2 Hz, 2H), 2.01-1.88
			(m, 3H), 1.86-1.78 (m, 2H), 1.76-1.66 (m, 3H), 0.96
			(t, J = 7.4 Hz, 2H).
370	378	methane- sulfonyl chloride
			Compound 370: oxazol-5-ylmethyl (3-fluoro-4-((6-
			(methylsulfonyl)-6-azaspiro[3.4]octan-2-
			yl)methyl)phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 438.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.42 (s,
			1H), 7.31 (s, 2H), 7.20-7.07 (m, 2H), 5.22 (s, 2H), 3.24-
			3.15 (m, 3H), 3.11 (s, 1H), 2.88-2.81 (m, 3H), 2.68-
			2.60 (m,, 2H), 2.09-2.00 (m, 1H), 1.97-1.86 (m, 3H),
			1.84-1.65 (m, 3H).
369	378	ethanesulfonyl chloride
			Compound 369: oxazol-5-ylmethyl (3-fluoro-4-((6-
			(ethylsulfonyl)-6-azaspiro[3.4]octan-2-
			yl)methyl)phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 452.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.93 (s, 1H), 8.41 (s,
			1H), 7.31-7.25 (m, 2H), 7.19-7.07 (m, 2H), 5.21 (s,
			2H), 3.25-3.18 (m, 3H), 3.12 (s, 1H), 3.02 (q, J = 7.6 Hz,
			3H), 2.05-1.85 (m, 4H), 1.84-1.78 (m 1H), 1.77-1.64
			(m, 3H), 1.17 (td, J = 7.3, 1.0 Hz, 3H).
385	30.3	dimethyl- carbamoyl chloride
			Compound 385: oxazol-5-ylmethyl (S)-(4-(1-
			(dimethylcarbamoyl)piperidin-3-yl)phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 373.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H), 8.42 (s,
			1H), 7.38 (d, J = 8.1 Hz, 2H), 7.31 (s, 1H), 7.18 (d, J = 8.4
			Hz, 2H), 5.21 (s, 2H), 3.55 (dd, J = 22.6, 11.9 Hz, 2H),
			2.73 (s, 8H), 1.87 (d, J = 11.2 Hz, 1H), 1.70 (d, J = 11.3
			Hz, 1H), 1.57 (p, J = 13.9, 13.1 Hz, 3H).
384	30.3	dimethyl- sulfamoyl chloride
			Compound 384: oxazol-5-ylmethyl (S)-(4-(1-(N,N-
			dimethylsulfamoyl)piperidin-3-yl)phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 409.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H), 8.42 (s,
			1H), 7.38 (d, J = 8.1 Hz, 2H), 7.30 (s, 1H), 7.20 (d, J = 8.3
			Hz, 2H), 5.21 (s, 2H), 3.52 (dd, J = 11.7 Hz, 2H), 2.86 (t,
			J = 11.5 Hz, 2H), 2.74 (s, 6H), 2.71-2.61 (m, 1H), 1.88-
			1.71 (m, 2H), 1.65-1.48 (m, 2H).
383	30.3	methyl carbono- chloridate
			Compound 383: methyl (S)-3-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)phenyl)piperidine-1-
			carboxylate.
			LCMS-ESI (POS.) m/z: 360.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H), 8.42 (s,
			1H), 7.39 (d, J = 8.1 Hz, 2H), 7.31 (s, 1H), 7.18 (d, J = 8.3
			Hz, 2H), 5.21 (s, 2H), 3.98 (s, 2H), 3.60 (s, 3H), 2.81 (s,
			2H), 2.57 (d, J = 11.5 Hz, 1H), 1.86 (d, J = 12.8 Hz, 1H),
			1.71 (d, J = 13.1 Hz, 1H), 1.62 (q, J = 11.7, 11.3 Hz, 1H),
			1.45 (d, J = 12.8 Hz, 1H).
382	30.3	methane- sulfonyl chloride
			Compound 382: oxazol-5-ylmethyl (S)-(4-(1-
			(methylsulfonyl)piperidin-3-yl)phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 380.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H), 8.43 (s,
			1H), 7.40 (d, J = 8.2 Hz, 2H), 7.31 (s, 1H), 7.22 (d, J = 8.3
			Hz, 2H), 5.22 (s, 2H), 3.59 (d, J = 12.2 Hz, 1H), 3.32 (s,
			2H), 2.88 (s, 2H), 2.71 (dd, J = 13.8, 10.2 Hz, 3H), 1.84 (s,
			1H), 1.89-1.79 (m, 1H), 1.59 (s, 1H), 1.54 (d, J = 11.3
			Hz, 1H).
381	30.3	acetic anhydride
			Compound 381: oxazol-5-ylmethyl (S)-(4-(1-
			acetylpiperidin-3-yl)phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 344.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H), 8.42 (s,
			1H), 7.44-7.34 (m, 2H), 7.30 (s, 1H), 7.20 (dd, J = 21.5,
			8.2 Hz, 2H), 5.21 (s, 2H), 4.47-4.33 (m, 1H), 3.78 (dd,
			J = 30.2, 13.3 Hz, 1H), 3.10-2.96 (m, 1H), 2.71-2.55 (m,
			1H), 2.01 (d, J = 5.6 Hz, 3H), 1.87 (d, J = 12.9 Hz, 1H),
			1.79-1.56 (m, 2H), 1.56-1.29 (m, 2H).
397	30.4	oxetan-3-one
			Compound 397: oxazol-5-ylmethyl (3-fluoro-4-((2-
			(oxetan-3-yl)-2-azaspiro[3.3]heptan-6-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 402.1 [M + H]+.
472	30.4	acetic anhydride
			Compound 472: oxazol-5-ylmethyl (4-((2-acetyl-2-
			azaspiro[3.3]heptan-6-yl)methyl)-3-
			fluorophenyl)carbamate
			LCMS-ESI (POS.) m/z: 388.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.42 (s,
			1H), 7.33-7.26 (m, 2H), 7.19-7.06 (m, 2H), 5.22 (s,
			2H), 4.07 (s, 1H), 3.98 (s, 1H), 3.79 (s, 1H), 3.69 (s, 1H),
			2.58 (d, J = 7.5 Hz, 2H), 2.37-2.27 (m, 1H), 2.24-2.12
			(m, 2H), 1.88-1.80 (m, 2H), 1.69 (s, 3H).
403	30.4	isobutyryl chloride
			Compound 403: oxazol-5-ylmethyl (3-fluoro-4-((2-
			isobutyryl-2-azaspiro[3.3]heptan-6-
			yl)methyl)phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 416.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.42 (s,
			1H), 7.33-7.27 (m, 2H), 7.18-7.09 (m, 2H), 5.22 (s,
			2H), 4.11 (s, 1H), 4.02 (s, 1H), 3.80 (s, 1H), 3.70 (s, 1H),
			2.58 (d, J = 7.5 Hz, 2H), 2.41-2.35 (m, 1H), 2.34-2.27
			(m, 1H), 2.24-2.12 (m, 2H), 1.89-1.80 (m, 2H), 0.93 (s,
			3H), 0.92 (s, 3H).
404	30.4	methane- sulfonyl chloride
			Compound 404: oxazol-5-ylmethyl (3-fluoro-4-((2-
			(methylsulfonyl)-2-azaspiro[3.3]heptan-6-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 425.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.43 (s,
			1H), 7.33-7.26 (m, 2H), 7.18-7.10 (m, 2H), 5.22 (s,
			2H), 3.84 (s, 2H), 3.75 (s, 2H), 3.30-3.28 (m, 1H), 2.92
			(s, 3H), 2.69-2.65 (m, 1H), 2.58 (d, J = 7.5 Hz, 1H), 2.37-
			2.27 (m, 2H), 2.25-2.15 (m, 1H), 1.89-1.81 (m, 1H).
386	30.4	ethanesulfonyl chloride
			Compound 386: oxazol-5-ylmethyl (4-((2-
			(ethylsulfonyl)-2-azaspiro[3.3]heptan-6-yl)methyl)-3-
			fluorophenyl)carbamate
			LCMS-ESI (POS.) m/z: 438.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.42 (s,
			1H), 7.32-7.26 (m, 2H), 7.18-7.08 (m, 2H), 5.22 (s,
			2H), 3.83 (s, 2H), 3.75 (s, 2H), 3.29 (s, 2H), 3.05 (q, J =
			7.4 Hz, 3H), 2.66 (s, 1H), 2.57 (d, J = 7.5 Hz, 1H), 2.35-
			2.30 (m, 2H), 1.18 (t, J = 7.4 Hz, 3H).
402	30.4	propionyl chloride
			Compound 402: oxazol-5-ylmethyl (3-fluoro-4-((2-
			propionyl-2-azaspiro[3.3]heptan-6-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 402.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.43 (s,
			1H), 7.33-7.27 (m, 2H), 7.18-7.11 (m, 2H), 5.23 (s,
			2H), 4.06 (s, 1H), 3.98 (s, 1H), 3.80 (s, 1H), 3.71 (s, 1H),
			3.30 (s, 2H), 2.70-2.65 (s, 1H), 2.59 (d, J = 7.5 Hz, 2H),
			2.35-2.31 (m, 1H), 2.23-2.14 (m, 1H), 1.99 (q, J = 7.5
			Hz, 3H), 1.89-1.81 (m, 2H).
399	30.4	dimethyl- sulfamoyl chloride
			Compound 399: oxazol-5-ylmethyl (4-((2-(N,N-
			dimethylsulfamoyl)-2-azaspiro[3.3]heptan-6-
			yl)methyl)-3-fluorophenyl)carbamate
			LCMS-ESI (POS.) m/z: 453.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.42 (s,
			1H), 7.34-7.26 (m, 2H), 7.18-7.09 (m, 2H), 5.22 (s,
			2H), 3.78 (s, 2H), 3.69 (s, 2H), 2.72-2.64z (m, 6H), 2.57
			(d, J = 7.5 Hz, 2H), 2.35-2.27 (m, 1H), 2.23-2.14 (m,
			2H), 1.84 (t, J = 9.8 Hz, 2H).
398	30.4	dimethyl- carbamoyl chloride
			Compound 398: oxazol-5-ylmethyl (4-((2-
			(dimethylcarbamoyl)-2-azaspiro[3.3]heptan-6-
			yl)methyl)-3-fluorophenyl)carbamate
			LCMS-ESI (POS.) m/z: 417.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.42 (s,
			1H), 7.33-7.26 (m, 2H), 7.19-7.09 (m, 2H), 5.76 (s,
			1H), 5.22 (s, 2H), 3.84 (s, 2H), 3.75 (s, 2H), 2.67 (s, 1H),
			2.57 (d, J = 7.5 Hz, 2H), 2.36-2.24 (m, 2H), 2.16 (t, J =
			9.9 Hz, 3H), 1.86-1.75 (m, 3H), 1.23 (s, 1H).
396	30.4	methyl carbono- chloridate
			Compound 396: methyl 6-(2-fluoro-4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)-2-
			azaspiro[3.3]heptane-2-carboxylate
			LCMS-ESI (POS.) m/z: 404.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.94 (s, 1H), 8.42 (s,
			1H), 7.33-7.26 (m, 2H), 7.16-7.08 (m, 2H), 5.22 (s,
			2H), 3.88 (s, 2H), 3.78 (s, 2H), 3.51 (s, 4H), 3.29 (s, 2H),
			2.67 (s, 2H), 3.35-2.25 (m, 2H).
401	30.4-a	acetic anhydride
			Compound 401: oxazol-5-ylmethyl (4-(2-acetyl-2-
			azaspiro[3.3]heptan-6-yl)-3-fluorophenyl)carbamate
			LCMS-ESI (POS.) m/z: 404.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.97 (s, 1H), 8.42 (s,
			1H), 7.31 (s, 1H), 7.30-7.15 (m, 3H), 5.22 (s, 2H), 4.23
			(s, 1H), 4.01 (s, 1H), 3.95 (s, 1H), 3.73 (s, 1H), 3.45
			(p, J = 8.9 Hz, 1H), 2.56-2.50 (m, 2H), 2.30-2.22 (m,
			2H), 1.73 (d, J = 10.8 Hz, 3H).
400	30.4-a	dimethyl- carbamoyl chloride
			Compound 400: oxazol-5-ylmethyl (4-(2-
			(dimethylcarbamoyl)-2-azaspiro[3.3]heptan-6-yl)-3-
			fluorophenyl)carbamate
			LCMS-ESI (POS.) m/z: 403.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.97 (s, 1H), 8.43 (s,
			1H), 7.31 (s, 1H), 7.31-7.14 (m, 3H), 5.23 (s, 2H), 4.01
			(s, 2H), 3.79 (s, 2H), 3.45 (p, J = 8.8 Hz, 1H), 2.74 (s, 6H),
			2.48-2.45 (m, 2H), 2.27-2.20 (m, 2H).
388	30.4-a	methane- sulfonyl chloride
			Compound 388: oxazol-5-ylmethyl (3-fluoro-4-(2-
			(methylsulfonyl)-2-azaspiro[3.3]heptan-6-
			yl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 410.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.97 (s, 1H), 8.42 (s,
			1H), 7.31 (s, 1H), 7.30-7.14 (m, 3H), 5.22 (s, 2H), 4.00
			(s, 2H), 3.78 (s, 2H), 3.46 (p, J = 8.8 Hz, 1H), 2.96 (s, 3H),
			2.57-2.52 (m, 2H), 2.27 (td, J = 9.7, 2.8 Hz, 2H).
387	30.4-a	dimethyl- sulfamoyl chloride
			Compound 387: oxazol-5-ylmethyl (4-(2-(N,N-
			dimethylsulfamoyl)-2-azaspiro[3.3]heptan-6-yl)-3-
			fluorophenyl)carbamate
			LCMS-ESI (POS.) m/z: 439.1 [M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.42 (s,
			1H), 7.31 (s, 1H), 7.30-7.12 (m, 3H), 5.22 (s, 2H), 3.95
			(s, 2H), 3.72 (s, 2H), 3.45 (p, J = 9.0 Hz, 1H), 2.72 (s, 6H),
			2.56-2.51 (m, 2H), 2.30-2.23 (m, 2H).
405	30.5	dimethyl- sulfamoyl chloride
			Compound 405: oxazol-5-ylmethyl (4-((8-(N,N-
			dimethylsulfamoyl)-8-azabicyclo[3.2.1]octan-3-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 449.1 [M + H]+
			1H NMR (400 MHz, Methanol-d4) δ 8.24 (s, 1H), 7.35 (t,
			J = 7.4 Hz, 2H), 7.25 (s, 1H), 7.11 (t, J = 8.4 Hz, 2H), 5.25
			(s, 2H), 4.12-3.95 (m, 2H), 2.79 (d, J = 4.5 Hz, 6H), 2.72
			(d, J = 7.5 Hz, 1H), 2.48 (d, J = 7.1 Hz, 1H), 2.26-1.97
			(m, 4H), 1.91 (t, J = 7.1 Hz, 1H), 1.69 (t, J = 7.0 Hz, 1H),
			1.66-1.56 (m, 1H), 1.56-1.39 (m, 2H).
406	30.5	methane- sulfonyl chloride
			Compound 406: oxazol-5-ylmethyl (4-((8-
			(methylsulfonyl)-8-azabicyclo[3.2.1]octan-3-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 420.1 [M + H]+
407	30.5	methyl carbono- chloridate
			Compound 407: methyl 3-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)-8-
			azabicyclo[3.2.1]octane-8-carboxylate
			LCMS-ESI (POS.) m/z: 400.1 [M + H]+
408	30.5	dimethyl- carbamoyl chloride
			Compound 408: oxazol-5-ylmethyl (4-((8-
			(dimethylcarbamoyl)-8-azabicyclo[3.2.1]octan-3-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 413.1 [M + H]+
409	30.5	isobutyryl chloride
			Compound 409: oxazol-5-ylmethyl (4-((8-isobutyryl-8-
			azabicyclo[3.2.1]octan-3-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 412.1 [M + H]+
410	30.5	acetic anhydride
			Compound 410: oxazol-5-ylmethyl (4-((8-acetyl-8-
			azabicyclo[3.2.1]octan-3-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 384.1 [M + H]+
389	30.5	morpholine-4- carbonyl chloride
			Compound 389: oxazol-5-ylmethyl (4-((8-(morpholine-
			4-carbonyl)-8-azabicyclo[3.2.1]octan-3-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 455.1[M + H]+
390	30.5	piperidine-1- carbonyl chloride
			Compound 390: oxazol-5-ylmethyl (4-((8-(piperidine-1-
			carbonyl)-8-azabicyclo[3.2.1]octan-3-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 453.1[M + H]+
391	30.5	pyrrolidine-1- carbonyl chloride
			Compound 391: oxazol-5-ylmethyl (4-((8-(pyrrolidine-
			1-carbonyl)-8-azabicyclo[3.2.1]octan-3-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 439.1[M + H]+
392	30.5	azetidine-1- carbonyl chloride
			Compound 392: oxazol-5-ylmethyl (4-((8-(azetidine-1-
			carbonyl)-8-azabicyclo[3.2.1]octan-3-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 425.1[M + H]+
393	30.5	azetidine-1- sulfonyl chloride
			Compound 393: oxazol-5-ylmethyl (4-((8-(azetidin-1-
			ylsulfonyl)-8-azabicyclo[3.2.1]octan-3-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 461.1[M + H]+
394	30.5	cyclobutane- sulfonyl chloride
			Compound 394: oxazol-5-ylmethyl (4-((8-
			(cyclobutylsulfonyl)-8-azabicyclo[3.2.1]octan-3-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 460.1[M + H]+
395	30.5	cyclopropane- sulfonyl chloride
			Compound 395: oxazol-5-ylmethyl (4-((8-
			(cyclopropylsulfonyl)-8-azabicyclo[3.2.1]octan-3-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 446.1[M + H]+
			1H NMR (400 MHz, Methanol-d4) δ 8.24 (s, 1H), 7.35 (t,
			J = 7.7 Hz, 2H), 7.11 (t, J = 9.0 Hz, 2H), 5.25 (s, 2H), 4.16
			(q, J = 3.4 Hz, 2H), 2.73 (d, J = 7.3 Hz, 1H), 2.57-2.38
			(m, 2H), 2.26-1.87 (m, 5H), 1.80-1.70 (m, 1H), 1.70-
			1.57 (m, 2H), 1.48 (td, J = 12.7, 2.7 Hz, 2H), 1.14-0.86
			(m, 4H).
411	30.6	dimethyl- carbamoyl chloride
			Compound 411: oxazol-5-ylmethyl (4-(1-
			(dimethylcarbamoyl)piperidin-4-yl)-3-
			fluorophenyl)carbamate
			LCMS-ESI (POS.) m/z: 391.1[M + H]+
412	30.6	propionyl chloride
			Compound 412: oxazol-5-ylmethyl (3-fluoro-4-(1-
			propionylpiperidin-4-yl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 376.1[M + H]+
413	30.6	acetic anhydride
			Compound 413: oxazol-5-ylmethyl (4-(1-
			acetylpiperidin-4-yl)-3-fluorophenyl)carbamate
			LCMS-ESI (POS.) m/z: 362.1[M + H]+
414	30.6	isobutyryl chloride
			Compound 414: oxazol-5-ylmethyl (3-fluoro-4-(1-
			isobutyrylpiperidin-4-yl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 390.1[M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.97 (s, 1H), 8.42 (s,
			1H), 7.31 (d, J = 6.1 Hz, 2H), 7.23 (t, J = 8.5 Hz, 1H),
			7.18-7.11 (m, 1H), 5.22 (s, 2H), 4.55 (d, J = 12.9 Hz,
			1H), 4.04 (d, J = 13.2 Hz, 1H), 3.12 (t, J = 12.9 Hz, 1H),
			3.04-2.83 (m, 2H), 2.58 (t, J = 12.4 Hz, 1H), 1.74 (t, J =
			17.4 Hz, 2H), 1.63-1.37 (m, 2H), 1.00 (dd, J = 10.9, 6.6
			Hz, 6H).
415	30.6	methane- sulfonyl chloride
			Compound 415: oxazol-5-ylmethyl (3-fluoro-4-(1-
			(methylsulfonyl)piperidin-4-yl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 398.1[M + H]+
416	30.6	dimethyl- sulfamoyl chloride
			Compound 416: oxazol-5-ylmethyl (4-(1-(N,N-
			dimethylsulfamoyl)piperidin-4-yl)-3-
			fluorophenyl)carbamate
			LCMS-ESI (POS.) m/z: 427.1[M + H]+
417	30.6	methyl carbono- chloridate
			Compound 417: methyl 4-(2-fluoro-4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)phenyl)piperidine-1-
			carboxylate
			LCMS-ESI (POS.) m/z: 378.1[M + H]+
444	30.7	acetic anhydride
			Compound 444: oxazol-5-ylmethyl (4-((4-acetyl-4-
			azaspiro[2.5]octan-7-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 384.1[M + H]+
443	30.7	methyl carbono- chloridate
			Compound 443: methyl 7-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)-4-
			azaspiro[2.5]octane-4-carboxylate
			LCMS-ESI (POS.) m/z: 400.1[M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.70 (s, 1H), 8.41 (s,
			1H), 7.33 (d, J = 8.1 Hz, 2H), 7.30 (s, 1H), 7.06 (d, J = 8.5
			Hz, 2H), 5.20 (s, 2H), 3.87 (d, J = 15.2 Hz, 1H), 3.57 (s,
			3H), 2.81 (t, J = 12.6, 2.0 Hz, 1H), 2.46-2.36 (m, 2H),
			1.95-1.82 (m, 1H), 1.57-1.44 (m, 2H), 1.13-0.95 (m,
			2H), 0.86 (dd, J = 13.0, 3.8 Hz, 1H), 0.78 (dt, J = 9.6, 6.2
			Hz, 1H), 0.48-0.40 (m, 1H), 0.36-0.28 (m, 1H).
442	30.7	dimethyl- carbamoyl chloride
			Compound 442: oxazol-5-ylmethyl (4-((4-
			(dimethylcarbamoyl)-4-azaspiro[2.5]octan-7-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 413.1[M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.70 (s, 1H), 8.41 (s,
			1H), 7.33 (d, J = 8.1 Hz, 2H), 7.29 (s, 1H), 7.06 (d, J = 8.5
			Hz, 2H), 5.20 (s, 2H), 3.41 (ddd, J = 13.1, 4.1, 2.2 Hz,
			1H), 2.87 (td, J = 13.3, 2.3 Hz, 1H), 2.68 (s, 6H), 2.44-
			2.36 (m, 2H), 1.88-1.75 (m, 2H), 1.49 (d, J =
			12.7 Hz, 1H), 0.97 (qd, J = 12.3, 4.1 Hz, 1H), 0.86-0.74
			(m, 1H), 0.69-0.58 (m, 2H), 0.36-0.29 (m, 1H), 0.27-
			0.20 (ddd, J = 9.2, 6.5, 4.1 Hz, 1H).
419	30.7	methane- sulfonyl chloride
			Compound 419: oxazol-5-ylmethyl (4-((4-
			(methylsulfonyl)-4-azaspiro[2.5]octan-7-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 420.1[M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.71 (s, 1H), 8.41 (s,
			1H), 7.34 (d, J = 8.1 Hz, 2H), 7.30 (s, 1H), 7.07 (d, J = 8.2
			Hz, 2H), 5.20 (s, 2H), 3.79-3.70 (m, 1H), 2.97-2.88 (m,
			1H), 2.94 (s, 3H), 2.47-2.38 (m, 2H), 1.94-1.82 (m,
			1H), 1.71 (t, J = 12.4 Hz, 1H), 1.54-1.47 (m, 1H), 1.44-
			1.37 (m, 1H), 1.29 (qd, J = 12.9, 3.8 Hz, 1H), 0.88-0.80
			(m, 1H), 0.79-0.71 (m, 1H), 0.52-0.44 (m, 1H), 0.40-
			0.32 (m, 1H).
418	30.7	ethanesulfonyl chloride
			Compound 418: oxazol-5-ylmethyl (4-((4-
			(ethylsulfonyl)-4-azaspiro[2.5]octan-7-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 434.1[M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.71 (s, 1H), 8.41 (s,
			1H), 7.33 (d, J = 8.1 Hz, 2H), 7.30 (s, 1H), 7.07 (d, J = 8.3
			Hz, 2H), 5.20 (s, 2H), 3.69-2.61 (m, 1H), 3.03-2.89 (m,
			3H), 2.46-2.40 (m, 2H), 1.93-1.81 (m, 1H), 1.67 (t, J =
			12.3 Hz, 1H), 1.56-1.48 (m, 1H), 1.35-1.19 (m, 2H),
			1.09 (t, J = 7.3 Hz, 3H), 0.87 (dd, J = 13.4, 2.9 Hz 1H),
			0.74 (dt, J = 9.6, 6.5 Hz, 1H), 0.51-0.45 (m, 1H), 0.40-
			0.33 (m, 1H).
440	30.7	dimethyl- sulfamoyl chloride
			Compound 440: oxazol-5-ylmethyl (4-((4-(N,N-
			dimethylsulfamoyl)-4-azaspiro[2.5]octan-7-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 449.1[M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.71 (s, 1H), 8.41 (s,
			1H), 7.33 (d, J = 8.1 Hz, 2H), 7.30 (s, 1H), 7.07 (d, J = 8.5
			Hz, 2H), 5.20 (s, 2H), 3.61-3.53 (m, 1H), 3.00-2.91 (m,
			1H), 2.58 (s, 6H), 2.46-2.40 (m, 2H), 1.92-1.82 (m,
			1H), 1.73 (td, J = 11.8, 1.3 Hz, 1H), 1.51-1.43 (m, 1H),
			1.37 (td, J = 12.5, 4.2 Hz, 1H), 1.22 (dt, J = 10.2, 5.8 Hz,
			1H), 0.87-0.81 (m, 1H), 0.71 (dt, J = 9.6, 6.2 Hz, 1H),
			0.55-047 (m, 1H), 0.40-0.32 (m, 1H).
420	426	methane- sulfonyl chloride
			Compound 420: oxazol-5-ylmethyl (4-((3-
			(methylsulfonyl)-3-azabicyclo[3.2.1]octan-8-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 420.1[M + H]+
421	426	methyl carbono- chloridate
			Compound 421: methyl 8-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)-3-
			azabicyclo[3.2.1]octane-3-carboxylate
			LCMS-ESI (POS.) m/z: 400.1[M + H]+
422	426	dimethyl- carbamoyl chloride
			Compound 422: oxazol-5-ylmethyl (4-((3-
			(dimethylcarbamoyl)-3-azabicyclo[3.2.1]octan-8-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 413.1[M + H]+
			1H NMR (400 MHz, Methanol-d4) δ 8.24 (s, 1H), 7.36 (d,
			J = 8.1 Hz, 2H), 7.25 (s, 1H), 7.19 (d, J = 8.5 Hz, 2H),
			5.25 (s, 2H), 3.51-3.39 (m, 4H), 2.96 (d, J = 7.4 Hz, 2H),
			2.81 (s, 6H), 2.04-1.91 (m, 3H), 1.78-1.56 (m, 4H).
423	426	isobutyryl chloride
			Compound 423: oxazol-5-ylmethyl (4-((3-isobutyryl-3-
			azabicyclo[3.2.1]octan-8-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 412.1[M + H]+
424	426	acetic anhydride
			Compound 424: oxazol-5-ylmethyl (4-((3-acetyl-3-
			azabicyclo[3.2.1]octan-8-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 384.1[M + H]+
			1H NMR (400 MHz, Methanol-d4) δ 8.24 (s, 1H), 7.37 (d,
			J = 8.1 Hz, 2H), 7.25 (s, 1H), 7.25-7.15 (m, 2H), 5.25 (s,
			2H), 4.08-3.92 (m, 1H), 3.66 (d, J = 12.7 Hz, 1H), 3.47
			(dd, J = 12.7, 2.8 Hz, 1H), 3.17 (d, J = 13.3 Hz, 1H), 2.92
			(d, J = 6.9 Hz, 2H), 2.11 (s, 3H), 2.10-1.97 (m, 3H), 1.88-
			1.71 (m, 2H), 1.65-1.45 (m, 2H).
427	30.9	ethanesulfonyl chloride
			Compound 427: oxazol-5-ylmethyl (4-(1-
			(ethylsulfonyl)piperidin-4-yl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 394.1[M + H]+
428	30.9	azetidine-1- sulfonyl chloride
			Compound 428: oxazol-5-ylmethyl (4-(1-(azetidin-1-
			ylsulfonyl)piperidin-4-yl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 421.1[M + H]+
429	30.9	azetidine-1- carbonyl chloride
			Compound 429: oxazol-5-ylmethyl (4-(1-(azetidine-1-
			carbonyl)piperidin-4-yl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 385.1[M + H]+
430	30.9	propionyl chloride
			Compound 430: oxazol-5-ylmethyl (4-(1-
			propionylpiperidin-4-yl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 358.1[M + H]+
431	30.9	cyclopropane- carbonyl chloride
			Compound 431: oxazol-5-ylmethyl (4-(1-
			(cyclopropanecarbonyl)piperidin-4-
			yl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 370.1[M + H]+
432	30.9	dimethyl- sulfamoyl chloride
			Compound 432: oxazol-5-ylmethyl (4-(1-(N,N-
			dimethylsulfamoyl)piperidin-4-yl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 409.1[M + H]+
433	30.8	dimethyl- sulfamoyl chloride
			Compound 433: oxazol-5-ylmethyl (4-((3-(N,N-
			dimethylsulfamoyl)-3-azabicyclo[3.1.1]heptan-6-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 435.1[M + H]+
434	30.8	methane- sulfonyl chloride
			Compound 434: oxazol-5-ylmethyl (4-((3-
			(methylsulfonyl)-3-azabicyclo[3.1.1]heptan-6-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 406.1[M + H]+
			1H NMR (400 MHz, Methanol-d4) δ 8.24 (s, 1H), 7.35 (d,
			J = 8.0 Hz, 2H), 7.25 (s, 1H), 7.16 (d, J = 8.3 Hz, 2H),
			5.25 (s, 2H), 3.67 (d, J = 10.4 Hz, 2H), 3.54 (d, J = 10.7,
			1.9 Hz, 2H), 2.96 (s, 3H), 2.71 (d, J = 7.7 Hz, 2H), 2.54 (q,
			J = 7.1 Hz, 1H), 2.51-2.37 (m, 2H), 2.15-2.05 (m, 1H),
			1.45 (d, J = 9.6 Hz, 1H).
435	30.8	methyl carbono- chloridate
			Compound 435: methyl 6-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)-3-
			azabicyclo[3.1.1]heptane-3-carboxylate
			LCMS-ESI (POS.) m/z: 386.1[M + H]+
436	30.8	dimethyl- carbamoyl chloride
			Compound 436: oxazol-5-ylmethyl (4-((3-
			(dimethylcarbamoyl)-3-azabicyclo[3.1.1]heptan-6-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 399.1[M + H]+
437	30.8	isobutyryl chloride
			Compound 437: oxazol-5-ylmethyl (4-((3-isobutyryl-3-
			azabicyclo[3.1.1]heptan-6-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 398.1[M + H]+
438	30.8	acetic anhydride
			Compound 438: oxazol-5-ylmethyl (4-((3-acetyl-3-
			azabicyclo[3.1.1]heptan-6-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 370.1[M + H]+
449	30.10	dimethyl- carbamoyl chloride
			Compound 449: oxazol-5-ylmethyl (4-((1-
			(dimethylcarbamoyl)piperidin-4-yl)methyl)-3-
			fluorophenyl)carbamate
			LCMS-ESI (POS.) m/z: 405.1[M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.42 (s,
			1H), 7.36-7.24 (m, 2H), 7.21-7.07 (m, 2H), 5.22 (s,
			2H), 3.49 (d, J = 13.1 Hz, 2H), 2.69 (s, 6H), 2.58 (t, J =
			12.3 Hz, 2H), 2.47 (d, J = 6.7 Hz, 2H), 1.66-1.57 (m,
			1H), 1.51 (d, J = 13.1 Hz, 2H), 1.21-1.01 (m, 2H).
445	Com- pound 426	acetic anhydride
			Compound 445: oxazol-5-ylmethyl (4-(3-acetyl-3-
			azabicyclo[3.2.1]octan-8-yl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 370.1 [M + H]+
448	30.10	methane- sulfonyl chloride
			Compound 448: oxazol-5-ylmethyl (3-fluoro-4-((1-
			(methylsulfonyl)piperidin-4-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 412.1[M + H]+
			1H NMR (400 MHz, Chloroform-d) δ 7.92 (s, 1H), 7.28 (s,
			1H), 7.20 (s, 1H), 7.18-6.90 (m, 2H), 6.66 (s, 2H), 5.24
			(d, J = 10.9 Hz, 2H), 3.77 (d, J = 11.6 Hz, 2H), 2.75 (s,
			3H), 2.65-2.50 (m, 4H), 1.73 (d, J = 13.4 Hz, 2H), 1.38
			(t, J = 12.5 Hz, 2H).
447	30.10	dimethyl- sulfamoyl chloride
			Compound 447: oxazol-5-ylmethyl (4-((1-(N,N-
			dimethylsulfamoyl)piperidin-4-yl)methyl)-3-
			fluorophenyl)carbamate
			LCMS-ESI (POS.) m/z: 441.1[M + H]+
450	30.10	methyl carbono- chloridate
			Compound 450: methyl 4-(2-fluoro-4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)piperidine-1-
			carboxylate
			LCMS-ESI (POS.) m/z: 392.1[M + H]+
451	30.10	acetic anhydride
			Compound 451: oxazol-5-ylmethyl (4-((1-
			acetylpiperidin-4-yl)methyl)-3-fluorophenyl)carbamate
			LCMS-ESI (POS.) m/z: 376.1[M + H]+
457	30.11	acetic anhydride
			Compound 457: oxazol-5-ylmethyl (4-((2-acetyl-2-
			azabicyclo[4.1.0]heptan-5-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 370.1[M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.72 (s, 1H), 8.41 (s,
			1H), 7.40-7.32 (m, 2H), 7.30 (s, 1H), 7.19-7.03 (m,
			2H), 5.20 (s, 2H), 4.74-3.88 (m, 1H), 3.71-2.71 (m,
			1H), 2.44-2.11 (m, 1H), 2.08-1.84 (m, 4H), 1.75-1.61
			(m, 1H), 1.58-1.40 (m, 1H), 1.27-0.95 (m, 3H), 0.89-
			0.70 (m, 1H), 0.42-0.17 (m, 1H).
456	30.11	methyl carbono- chloridate
			Compound 456: methyl 5-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)-2-
			azabicyclo[4.1.0]heptane-2-carboxylate
			LCMS-ESI (POS.) m/z: 386.1[M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.71 (s, 1H), 8.41 (s,
			1H), 7.39-7.31 (m, 2H), 7.30 (s, 1H), 7.19-7.03 (m,
			2H), 5.20 (s, 2H), 3.76-3.51 (m, 4H), 2.85-2.32 (m,
			1H), 2.18-1.82 (m, 1H), 1.77-1.37 (m, 2H), 1.25-0.83
			(m, 4H), 0.76-0.62 (m, 1H), 0.37-0.16 (m, 1H).
454	30.11	dimethyl- carbamoyl chloride
			Compound 454: oxazol-5-ylmethyl (4-((2-
			(dimethylcarbamoyl)-2-azabicyclo[4.1.0]heptan-5-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 399.1[M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.71 (s, 1H), 8.42 (s,
			1H), 7.40-7.32 (m, 2H), 7.30 (s, 1H), 7.18-7.02 (m,
			2H), 5.20 (s, 2H), 3.31-3.24 (m, 1H), 2.83-2.62 (m,
			7H), 2.43-2.30 (m, 1H), 2.15-2.03 (m, 1H), 1.51-1.37
			(m, 1H), 1.31-1.18 (m, 1H), 1.14-1.02 (m, 2H), 1.01-
			0.89 (m, 1H), 0.88-0.71 (m, 1H), 0.38-0.24 (m, 1H).
453	30.11	methane- sulfonyl chloride
			Compound 453: oxazol-5-ylmethyl (4-((2-
			(methylsulfonyl)-2-azabicyclo[4.1.0]heptan-5-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 406.1[M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.72 (s, 1H), 8.42 (s,
			1H), 7.35 (d, J = 7.7 Hz, 2H), 7.30 (s, 1H), 7.19-7.04 (m,
			2H), 5.20 (s, 2H), 3.63-3.07 (m, 1H), 2.93-2.55 (m,
			5H), 1.91-1.39 (m, 2H), 1.27-0.95 (m, 4H), 0.89-0.64
			(m, 1H), 0.60-0.44 (m, 1H).
458	320	morpholine-4- carbonyl chloride
			Compound 458: oxazol-5-ylmethyl (4-((1-(morpholine-
			4-carbonyl)piperidin-4-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 429.1[M + H]+
459	320	cyclobutane- sulfonyl chloride
			Compound 459: oxazol-5-ylmethyl (4-((1-
			(cyclobutylsulfonyl)piperidin-4-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 434.1[M + H]+
460	320	cyclopropane- sulfonyl chloride
			Compound 460: oxazol-5-ylmethyl (4-((1-
			(cyclopropylsulfonyl)piperidin-4-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 420.1[M + H]+
461	320	piperidine-1- carbonyl chloride
			Compound 461: oxazol-5-ylmethyl (4-((1-(piperidine-1-
			carbonyl)piperidin-4-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 427.1[M + H]+
462	320	pyrrolidine-1- carbonyl chloride
			Compound 462: oxazol-5-ylmethyl (4-((1-(pyrrolidine-
			1-carbonyl)piperidin-4-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 413.1[M + H]+
464	320	propane-2- sulfonyl chloride
			Compound 464: oxazol-5-ylmethyl (4-((1-
			(isopropylsulfonyl)piperidin-4-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 422.1[M + H]+
465	320	azetidine-1- sulfonyl chloride
			Compound 465: oxazol-5-ylmethyl (4-((1-(azetidin-1-
			ylsulfonyl)piperidin-4-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 435.1[M + H]+
469	320	cyclobutane- carboxylic acid
			Compound 469: oxazol-5-ylmethyl (4-((1-
			(cyclobutanecarbonyl)piperidin-4-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 398.1[M + H]+
470	320	3,3- difluorocyclo- butane-1- carboxylic acid
			Compound 470: oxazol-5-ylmethyl (4-((1-(3,3-
			difluorocyclobutane-1-carbonyl)piperidin-4-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 334.1[M + H]+
471	320	2- (bromomethyl) oxetane
			Compound 471: oxazol-5-ylmethyl (4-((1-(oxetan-2-
			ylmethyl)piperidin-4-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 386.1[M + H]+
380	30.3	oxetan-3-one
			Compound 380: oxazol-5-ylmethyl (S)-(4-(1-(oxetan-3-
			yl)piperidin-3-yl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 358.1[M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.72 (s, 1H), 8.42 (s,
			1H), 7.39-7.28 (m, 3H), 7.17 (d, J = 8.2 Hz, 2H), 5.21 (s,
			2H), 4.57-4.39 (m, 4H), 3.39 (p, J = 6.5 Hz, 1H), 2.74-
			2.63 (m, 3H), 1.77 (s, 3H), 1.72 (d, J = 13.7 Hz, 1H), 1.58
			(q, J = 12.4 Hz, 1H), 1.41 (td, J = 12.2, 3.8 Hz, 1H).
441	30.7	oxetan-3-one
			Compound 441: oxazol-5-ylmethyl (4-((4-(oxetan-3-yl)-
			4-azaspiro[2.5]octan-7-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 398.1[M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.69 (s, 1H), 8.41 (s,
			1H), 7.32 (d, J = 8.0 Hz, 2H), 7.29 (s, 1H), 7.08-7.00 (m,
			2H), 5.19 (s, 2H), 4.45-4.39 (m, 3H), 4.34 (dd, J = 7.2,
			5.6 Hz, 1H), 4.19 (p, J = 7.1 Hz, 1H), 2.69-2.60 (m, 1H),
			2.44-2.36 (m, 2H), 1.80-1.69 (m, 1H), 1.64 (td, J =
			12.1, 11.6, 1.8 Hz, 1H), 1.28-1.12 (m, 3H), 0.58 (dd, J =
			12.4, 3.3 Hz, 1H), 0.55-0.48 (m, 1H), 0.37-0.29 (m,
			1H), 0.25-0.18 (m, 1H), 0.10-0.03 (m, 1H).
425	426	oxetan-3-one
			Compound 425: oxazol-5-ylmethyl (4-((3-(oxetan-3-yl)-
			3-azabicyclo[3.2.1]octan-8-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 398.1[M + H]+
439	30.8	oxetan-3-one
			Compound 439: oxazol-5-ylmethyl (4-((3-(oxetan-3-yl)-
			3-azabicyclo[3.1.1]heptan-6-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 384.1[M + H]+
452	30.10	oxetan-3-one
			Compound 452: oxazol-5-ylmethyl (3-fluoro-4-((1-
			(oxetan-3-yl)piperidin-4-yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 390.1[M + H]+
455	30.11	oxetan-3-one
			Compound 455: oxazol-5-ylmethyl (4-((2-(oxetan-3-yl)-
			2-azabicyclo[4.1.0]heptan-5-
			yl)methyl)phenyl)carbamate
			LCMS-ESI (POS.) m/z: 384.1[M + H]+
			1H NMR (400 MHz, DMSO-d6) δ 9.71 (s, 1H), 8.41 (s,
			1H), 7.34 (d, J = 8.0 Hz, 2H), 7.30 (s, 1H), 7.14-7.02 (m,
			2H), 5.20 (s, 2H), 4.62-4.33 (m, 4H), 3.85-3.76 (m,
			1H), 2.47-2.00 (m, 3H), 1.85-0.69 (m, 7H), 0.34-0.24
			(m, 1H).
446	30.10	isopropyl carbono- chloridate
			Compound 446: isopropyl 4-(4-(((oxazol-5-
			ylmethoxy)carbonyl)amino)benzyl)piperidine-1-
			carboxylate
			LCMS-ESI (POS.) m/z: 402.1[M + H]+
468	30.10	Triphosgene azetidine
			Compound 468: oxazol-5-ylmethyl (4-((1-(azetidine-1-
			carbonyl)piperidin-4-yl)methyl)phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 399.1[M + H]+
463	30.10	Triphosgene 3,3-difluoro- azetidine
			Compound 463: oxazol-5-ylmethyl (4-((1-(3,3-
			difluoroazetidine-1-carbonyl)piperidin-4-
			yl)methyl)phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 435.1[M + H]+
467	30.10	F3CCH2OTf
			Compound 467: thiazol-5-ylmethyl (4-((1-(2,2,2-
			trifluoroethyl)piperidin-4-yl)methyl)phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 414.1[M + H]+
466	30.10	oxetan-3-one
			Compound 466: thiazol-5-ylmethyl (4-((1-(oxetan-3-
			yl)piperidin-4-yl)methyl)phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 388.1[M + H]+

Amide Coupling

Example M

Preparation of (4-chlorophenyl)methyl N-(4-{[(2-methylpyridin-4-yl)formamido]methyl}phenyl)carbamate (Compound 173)

To a solution of (4-chlorophenyl)methyl N-[4-(aminomethyl)phenyl]carbamate hydrochloride (100 mg, 0.31 mmol) and N,N-diisopropylethylamine (0.21 mL, 1.2 mmol) in dimethylformamide (1 mL) was added 2-methylpyridine-4-carboxylic acid (96.4 mg, 0.71 mmol), 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (151.1 mg, 0.40 mmol), and stirred at rt for 2.5 h, diluted with water, saturated sodium bicarbonate, and extracted with DCM. The combined organic layers were dried over sodium sulfate, concentrated, and purified by silica gel chromatography using a 0-10% MeOH/DCM gradient, concentrated, and re-purified by silica gel chromatography using a 0-100% EtOAc/Hex gradient to yield (4-chlorophenyl)methyl N-(4-{[(2-methylpyridin-4-yl)formamido]methyl}phenyl)carbamate (21.0 mg, 0.05 mmol, 17% yield). LCMS-APCI (POS.) m/z: 410.1 [M+H]⁺. ¹H NMR (400 MHz, DMSO-d₆) δ 9.76 (s, 1H), 9.19 (t, J 6.1 Hz, 1H), 8.57 (d, J=5.1 Hz, 1H), 7.65 (s, 1H), 7.56 (d, J=5.2 Hz, 1H), 7.48-7.44 (m, 4H), 7.41 (d, J 8.3 Hz, 2H), 7.23 (d, J 8.1 Hz, 2H), 5.13 (s, 2H), 4.41 (d, J=5.9 Hz, 2H), 2.53 (s, 3H).

Compounds in the following table were prepared in a similar manner as Compound 173, using the Intermediate and acid as listed.

Co	Intermediate
#	amine	Acid	Structure, Name and Data
21	15.2	6-methylpyridine-3- carboxylic acid
			Compound 21: (4-chlorophenyl)methyl N-
			(4-{[(6-methylpyridin-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 410.0 [M + H]+. 1H
			NMR (300 MHz, DMSO-d6) δ 9.74 (s, 1H),
			9.06 (t, J = 5.9 Hz, 1H), 8.90 (m, J = 2.3, 0.8 Hz,
			1H), 8.09 (m, J = 8.1, 2.3 Hz, 1H), 7.50-
			7.30 (m, 7H), 7.28-7.18 (m, 2H), 5.12 (s, 2H),
			4.40 (d, J = 5.9 Hz, 2H),2.50 (s, 3H).
272	15.2	picolinic acid
			Compound 272: (4-chlorophenyl)methyl N-
			{4-[(pyridin-2-
			ylformamido)methyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 396.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			9.24 (t, J = 6.2 Hz 1H), 8.64 (d, J = 4.7 Hz,
			1H), 8.08-7.94 (m, 2H), 7.60 (t, J = 6.1 Hz,
			1H), 7.49-7.42 (m, 4H), 7.39 (d, J = 8.2 Hz,
			2H), 7.24 (d, J = 8.1 Hz, 2H), 5.12 (s, 2H),
			4.42 (d, J = 6.4 Hz, 2H).
248	15.2	pyridazine-3-carboxylic acid
			Compound 248: (4-chlorophenyl)methyl N-
			{4-[(pyridazin-3-
			ylformamido)methyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 397.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.80-9.70 (m,
			2H), 9.41 (d, J = 4.9 Hz, 1H), 8.21 (d, J = 8.5 Hz,
			1H), 7.91 (dd, J = 8.4, 5.1 Hz, 1H), 7.48-
			7.42 (m, 4H), 7.40 (d, J = 8.3 Hz, 2H), 7.27
			(d, J = 8.3 Hz, 2H), 5.12 (s, 2H), 4.46 (d, J =
			6.3 Hz, 2H).
162	15.2	2-methoxypyrimidine- 5-carboxylic acid
			Compound 162: (4-chlorophenyl)methyl N-
			(4-{[(2-methoxypyrimidin-5-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 427.1 [M + H]+ .. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			9.11 (t, J = 5.9 Hz, 1H), 9.02 (s, 2H), 7.49-
			7.44 (m, 4H), 7.41 (d, J = 19.7 Hz, 2H), 7.25
			(d, J = 8.2 Hz, 2H), 5.13 (s, 2H), 4.42 (d, J =
			5.8 Hz, 2H), 3.98 (s, 3H).
185	15.2	6- (difluoromethyl) nicotinic acid
			Compound 185: (4-chlorophenyl)methyl N-
			[4-({[6-(difluoromethyl)pyridin-3-
			yl]formamido}methyl)phenyl]carbamate.
			LCMS-APCI (POS.) m/z: 446.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			9.30 (d, J = 5.3 Hz, 1H), 9.11 (s, 1H), 8.40
			(d, J = 8.5 Hz, 1H), 7.82 (d, J = 8.5 Hz, 1H),
			7.48-7.43 (m, 4H), 7.42 (d, J = 17.5 Hz, 2H),
			7.26 (d, J = 8.2 Hz, 2H), 7.03 (t, J = 55.0 Hz,
			1H), 5.13 (s, 2H), 4.44 (d, J = 5.7 Hz, 2H).
211	15.2	2,4-dimethyloxazole-5- carboxylic acid
			Compound 211: (4-chlorophenyl)methyl N-
			(4-{[(2,4-dimethyl-1,3-oxazol-5-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 414.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			8.76 (t, J = 6.6 Hz, 1H), 7.49-7.42 (m, 4H),
			7.39 (d, J = 8.1 Hz, 2H), 7.20 (d, J = 8.1 Hz,
			2H), 5.12 (s, 2H), 4.30 (d, J = 6.1 Hz, 2H),
			2.41 (s, 3H), 2.30 (s, 3H).
140	15.2	3,4-dimethylisoxazole- 5-carboxylic acid
			Compound 140: (4-chlorophenyl)methyl N-
			(4-{[(3,4-dimethyl-1,2-oxazol-5-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 414.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.79 (s, 1H),
			8.45 (t, J = 6.0 Hz, 1H), 7.50-7.45 (m, 4H),
			7.43 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.1 Hz,
			2H), 5.14 (s, 2H), 4.36 (d, J = 5.8 Hz, 2H),
			2.49 (s, 3H), 2.29 (s, 3H).
234	15.2	6-isopropylnicotinic acid
			Compound 234: (4-chlorophenyl)methyl N-
			(4-{[(6-isopropylpyridin-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 438.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			9.10 (t, J = 5.6 Hz, 1H), 8.95 (s, 1H), 8.16
			(d, J = 8.1 Hz 1H), 7.48-7.44 (m, 4H), 7.41
			(d, J = 8.1 Hz, 3H), 7.23 (d, J = 8.1 Hz, 2H),
			5.13 (s, 2H), 4.42 (d, J = 5.8 Hz, 2H), 3.08
			(sept, J = 7.0 Hz, 1H), 1.24 (d, J = 6.9 Hz, 6H).
294	15.2	5-methyloxazole-2- carboxylic acid
			Compound 294: (4-chlorophenyl)methyl N-
			(4-{[(5-methyl-1,3-oxazol-2-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 400.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			9.27 (t, J = 6.4 Hz, 1H), 7.49-7.42 (m, 4H),
			7.39 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 8.5 Hz,
			2H), 7.06 (s, 1H), 5.13 (s, 2H), 4.33 (d, J =
			6.3 Hz, 2H), 2.37 (s, 3H).
297	15.2	2-(oxazol-2-yl)acetic acid
			Compound 297: (4-chlorophenyl)methyl N-
			(4-{[2-(1,3-oxazol-2-
			yl)acetamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 400.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			8.63 (t, J = 5.1 Hz, 1H), 8.03 (s, 1H), 7.49-
			7.43 (m, 4H), 7.41 (d, J = 8.1 Hz, 2H), 7.18
			(d, J = 8.2 Hz, 2H), 7.14 (s, 1H), 5.13 (s, 2H),
			4.22 (d, J = 5.7 Hz, 2H), 3.73 (s, 2H).
315	15.2	2-(1-methyl-1H- pyrazol-4-yl)acetic acid
			Compound 315: (4-chlorophenyl)methyl N-
			(4-{[2-(1-methylpyrazol-4-
			yl)acetamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 413.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.30 (s, 1H), 7.50 (s, 1H), 7.48-7.42 (m, 4H),
			7.38 (d, J = 8.3 Hz, 2H), 7.25 (s, 1H), 7.13
			(d, J = 8.1 Hz, 2H), 5.13 (s, 2H), 4.17 (d, J =
			5.8 Hz, 2H), 3.77 (s, 3H), 3.26 (s, 2H).
295	15.2	2-(1-methyl-1H- pyrazol-3-yl)acetic acid
			Compound 295: (4-chlorophenyl)methyl N-
			(4-{[2-(1-methylpyrazol-3-
			yl)acetamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 413.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.34 (t, J = 6.0 Hz, 1H), 7.55 (s, 1H), 7.49-
			7.42 (m, 4H), 7.38 (d, J = 8.1 Hz, 2H), 7.15
			(d, J = 8.0 Hz, 2H), 6.07 (s, 1H), 5.13 (s, 2H),
			4.18 (d, J = 5.7 Hz, 2H), 3.76 (s, 3H), 3.39 (s,
			2H).
334	15.2	2-(1H-pyrazol-1- yl)acetic acid
			Compound 334: (4-chlorophenyl)methyl N-
			(4-{[2-(pyrazol-1-
			yl)acetamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 399.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			8.48 (t, J = 6.0 Hz 1H), 7.71 (s, 1H), 7.49-
			7.43 (s, 5H), 7.40 (d, J = 8.1 Hz, 2H), 7.17
			(d, J = 8.2 Hz, 2H), 6.25 (s, 1H), 5.13 (s, 2H),
			4.83 (s, 2H), 4.22 (d, J = 5.6 Hz, 2H).
209	15.2	4-methyloxazole-5- carboxylic acid
			Compound 209: (4-chlorophenyl)methyl N-
			(4-{[(4-methyl-1,3-oxazol-5-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 400.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.90 (t, J = 5.8 Hz 1H), 8.41 (s, 1H), 7.48-
			7.42 (m, 4H), 7.39 (d, J = 8.1 Hz, 2H), 7.21
			(d, J = 8.1 Hz, 2H), 5.13 (s, 2H), 4.33 (d, J =
			6.1 Hz, 2H), 2.36 (s, 3H).
268	15.2	4-methylisoxazole-5- carboxylic acid
			Compound 268: (4-chlorophenyl)methyl N-
			(4-{[(4-methyl-1,2-oxazol-5-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 400.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			9.30 (t, J = 6.2 Hz 1H), 8.62 (s, 1H), 7.49-
			7.43 (m, 4H), 7.40 (d, J = 8.2 Hz, 2H), 7.22
			(d, J = 8.3 Hz, 2H), 5.13 (s, 2H), 4.35 (d, J =
			6.1 Hz, 2H), 2.22 (s, 3H).
271	15.2	5-fluoronicotinic acid
			Compound 271: (4-chlorophenyl)methyl N-
			(4-{[(5-fluoropyridin-3-
			yl)formamido]methyl}phenyl). LCMS-
			APCI (POS.) m/z: 414.1 [M + H]+. 1H NMR
			(400 MHz, DMSO-d6) δ 9.76 (s, 1H), 9.25
			(t, J = 5.5 Hz, 1H), 8.92 (s, 1H), 8.74 (s, 1H),
			8.11 (d, J = 9.6 Hz, 1H), 7.48-7.44 (m, 4H),
			7.42 (d, J = 8.1 Hz, 2H), 7.25 (d, J = 8.2 Hz,
			2H), 5.13 (d, J = 2.2 Hz, 2H), 4.43 (d, J =
			6.0 Hz, 2H).
205	15.2	1-methyl-1H-pyrazole- 5-carboxylic acid
			Compound 205: (4-chlorophenyl)methyl N-
			(4-{[(2-methylpyrazol-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 399.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			8.94 (t, J = 5.7 Hz 1H), 7.49-7.43 (m, 5H),
			7.41 (d, J = 8.1 Hz, 2H), 7.22 (d, J = 8.1 Hz,
			2H), 6.88 (s, 1H), 5.13 (s, 2H), 4.36 (d, J =
			5.9 Hz, 2H), 4.05 (d, J = 2.5 Hz, 3H).
311	15.2	2-(oxazol-5-yl)acetic acid
			Compound 311: (4-chlorophenyl)methyl N-
			(4-{[2-(1,3-oxazol-5-
			yl)acetamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 400.3 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			8.53 (t, J = 5.6 Hz, 1H), 8.25 (s, 1H), 7.49-
			7.43 (m, 4H), 7.40 (d, J = 8.0 Hz, 2H), 7.16
			(d, J = 8.1 Hz, 2H), 6.96 (s, 1H), 5.13 (s, 2H),
			4.21 (d, J = 5.6 Hz, 2H), 3.64 (s, 2H).
126	15.2	isonicotinic acid
			Compound 126: (4-chlorophenyl)methyl N-
			{4-[(pyridin-4-
			ylformamido)methyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 396.4 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			9.27 (t, J = 5.9 Hz, 1H), 8.73 (s, 2H), 7.79 (s,
			2H), 7.49-7.44 (m, 4H), 7.41 (d, J = 8.4 Hz,
			2H), 7.24 (d, J = 8.3 Hz, 2H), 5.13 (s, 2H),
			4.42 (d, J = 5.8 Hz, 2H).
321	15.2	5-methyloxazole-4- carboxylic acid
			Compound 321: (4-chlorophenyl)methyl N-
			(4-{[(5-methyl-1,3-oxazol-4-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 400.3 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
			8.62 (t, J = 6.5 Hz, 1H), 8.32 (s, 1H), 7.48-
			7.41 (m, 4H), 7.38 (d, J = 8.2 Hz, 2H), 7.21
			(d, J = 8.1 Hz, 2H), 5.12 (s, 2H), 4.32 (d, J =
			6.0 Hz, 2H), 2.56 (d, J = 2.5 Hz, 3H).
330	15.2	2-(isoxazol-4-yl)acetic acid
			Compound 330: (4-chlorophenyl)methyl N-
			(4-{[2-(1,2-oxazol-4-
			yl)acetamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 400.3 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			8.75 (s, 1H), 8.53-8.42 (m, 2H), 7.50-7.43
			(m, 4H), 7.40 (d, J = 8.1 Hz, 2H), 7.16 (d, J =
			8.1 Hz, 2H), 5.13 (s, 2H), 4.20 (d, J = 4.1 Hz,
			2H), 3.38 (s, 2H).
225	15.2	1,3-dimethyl-1H- pyrazole-5-carboxylic acid
			Compound 225: (4-chlorophenyl)methyl N-
			(4-{[(2,5-dimethylpyrazol-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 413.3 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			8.86 (s, 1H), 7.49-7.44 (m, 4H), 7.41 (d, J =
			8.1 Hz, 2H), 7.21 (d, J = 8.1 Hz, 2H), 6.64 (s,
			1H), 5.14 (s, 2H), 4.34 (d, J = 4.8 Hz, 2H),
			3.97 (s, 3H), 2.15 (s, 3H).
45	15.2	1,4-dimethyl-1H- pyrazole-5-carboxylic acid
			Compound 45: (4-chlorophenyl)methyl N-
			(4-{[(2,4-dimethylpyrazol-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 413.4 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H),
			8.61 (s, 1H), 7.49-7.44 (m, 4H), 7.42 (d, J =
			7.6 Hz, 2H), 7.27-7.21 (m, 3H), 5.13 (s, 2H),
			4.38 (d, J = 5.5 Hz, 2H), 3.84 (s, 3H), 2.09 (s,
			3H).
167	15.2	1-ethyl-1H-pyrazole-5- carboxylic acid
			Compound 167: (4-chlorophenyl)methyl N-
			(4-{[(2-ethylpyrazol-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 413.3 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			8.93 (t, J = 7.3 Hz, 1H), 7.49-7.44 (m, 5H),
			7.41 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.3 Hz,
			2H), 6.86 (d, J = 2.7 Hz, 1H), 5.13 (s, 2H),
			4.50 (q, J = 7.5 Hz, 2H), 4.36 (d, J = 5.8 Hz,
			2H), 1.29 (t, J = 6.8 Hz, 3H).
82	15.2	6-ethylnicotinic acid
			Compound 82: (4-chlorophenyl)methyl N-
			(4-{[(6-ethylpyridin-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 424.4 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			9.08 (s, 1H), 8.95 (s, 1H), 8.15 (d, J = 8.5 Hz,
			1H), 7.49-7.43 (m, 4H), 7.43-7.36 (m, 3H),
			7.23 (d, J = 8.3 Hz, 2H), 5.13 (s, 2H), 4.42 (s,
			2H), 2.81 (q, J = 8.0 Hz, 2H), 1.28-1.20 (m,
			3H).
195	15.2	5-methoxy-6- methylnicotinic acid
			Compound 195: (4-chlorophenyl)methyl N-
			(4-{[(5-methoxy-6-methylpyridin-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 440.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			9.09 (t, J = 5.9 Hz, 1H), 8.52 (d, J = 1.8 Hz,
			1H), 7.73 (d, J = 1.7 Hz, 1H), 7.48-7.43 (m,
			4H), 7.41 (d, J = 8.6 Hz, 2H), 7.24 (d, J =
			8.6 Hz, 2H), 5.13 (s, 2H), 4.43 (d, J = 5.8 Hz,
			2H), 3.87 (s, 3H), 2.40 (s, 3H).
301	15.2	1-isopropyl-1H- pyrazole-5-carboxylic acid
			Compound 301: (4-chlorophenyl)methyl N-
			(4-{[(2-isopropylpyrazol-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-ESI (POS.) m/z: 427.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			8.76 (t, J = 6.0 Hz, 1H), 8.00 (s, 1H), 7.58 (s,
			1H), 7.48-7.42 (m, 4H), 7.40 (d, J = 8.3 Hz,
			2H), 7.21 (d, J = 8.6 Hz, 2H), 5.24 (p, J = 6.7 Hz,
			1H), 5.13 (s, 2H), 4.34 (d, J = 6.0 Hz, 2H),
			1.41 (s, 3H), 1.39 (s, 3H).
343	15.2	4-cyclopropyloxazole- 5-carboxylic acid
			Compound 343: (4-chlorophenyl)methyl N-
			(4-{[(4-cyclopropyl-1,3-oxazol-5-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 426.3 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.86 (t, J = 6.2 Hz, 1H), 8.34 (s, 1H), 7.48-
			7.42 (m, 4H), 7.40 (d, J = 8.3 Hz, 2H), 7.22
			(d, J = 8.6 Hz, 2H), 5.13 (s, 2H), 4.34 (d, J =
			6.1 Hz, 2H), 2.62 (td, J = 8.3, 4.3 Hz, 1H), 0.98-
			0.92 (m, 2H), 0.86-0.80 (m, 2H).
345	15.2	3-(difluoromethyl)-1- methyl-1H-pyrazole-5- carboxylic acid
			Compound 345: (4-chlorophenyl)methyl N-
			[4-({[5-(difluoromethyl)-2-methylpyrazol-
			3-yl]formamido}methyl)phenyl]carbamate.
			LCMS-APCI (POS.) m/z: 449.3 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			9.10 (t, J = 6.0 Hz, 1H), 7.48-7.44 (m, 4H),
			7.42 (d, J = 8.5 Hz, 2H), 7.23 (d, J = 8.6 Hz,
			2H), 7.15 (t, J = 1.0 Hz, 1H), 7.01 (t, J = 54.6 Hz,
			1H), 5.13 (s, 2H), 4.37 (d, J = 5.9 Hz, 2H),
			4.09 (s, 3H).
158	15.2	6-methoxynicotinic acid
			Compound 158: (4-chlorophenyl)methyl N-
			(4-{[(6-methoxypyridin-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 426.3 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			8.98 (t, J = 6.0 Hz, 1H), 8.69 (s, 1H), 8.15
			(d, J = 8.6 Hz, 1H), 7.49-7.44 (m, 4H), 7.41
			(d, J = 8.1 Hz, 2H), 7.23 (d, J = 8.1 Hz, 2H),
			6.89 (d, J = 8.8 Hz, 1H), 5.13 (s, 2H), 4.40
			(d, J = 5.8 Hz, 2H), 3.90 (s, 3H).
245	15.2	2-methoxy-6- methylnicotinic acid
			Compound 245: (4-chlorophenyl)methyl N-
			(4-{[(2-methoxy-6-methylpyridin-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 440.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			8.63 (t, J = 8.1 Hz 1H), 8.06 (d, J = 7.6 Hz,
			1H), 7.49-7.43 (m, 4H), 7.40 (d, J = 8.2 Hz,
			2H), 7.23 (d, J = 8.1 Hz, 2H), 6.97 (d, J = 7.6 Hz,
			1H), 5.13 (s, 2H), 4.42 (d, J = 6.0 Hz, 2H),
			3.95 (s, 3H), 2.44 (s, 3H).
214	15.2	5-methylpyridine-2- carboxylic acid
			Compound 214: (4-chlorophenyl)methyl N-
			(4-{[(5-methylpyridin-2-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 410.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			9.16 (t, J = 6.5 Hz, 1H), 8.48 (s, 1H), 7.94 (d,
			J = 8.0 Hz, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.50-
			7.43 (m, 4H), 7.39 (d, J = 8.1 Hz, 2H), 7.24
			(d, J = 8.2 Hz, 2H), 5.13 (s, 2H), 4.41 (d, J =
			6.4 Hz, 2H), 2.38 (s, 3H).
255	15.2	1-methylpyrazole-3- carboxylic acid
			Compound 255: (4-chlorophenyl)methyl N-
			(4-{[(1-methylpyrazol-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 399.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
			8.54 (t, J = 6.3 Hz, 1H), 7.77 (d, J = 2.1 Hz,
			1H), 7.48-7.44 (m, 4H), 7.38 (d, J = 8.2 Hz,
			2H), 7.21 (d, J = 8.3 Hz, 2H), 6.61 (d, J = 2.1 Hz,
			1H), 5.13 (s, 2H), 4.33 (d, J = 6.3 Hz, 2H),
			3.89 (s, 3H).
207	15.2	3-fluoropyridine-2- carboxylic acid
			Compound 207: (4-chlorophenyl)methyl N-
			(4-{[(3-fluoropyridin-2-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 413.9 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			9.15 (t, J = 6.3 Hz, 1H), 8.48 (d, J = 4.5 Hz,
			1H), 7.87 (t, J = 9.7 Hz, 1H), 7.72-7.62 (m,
			1H), 7.49-7.38 (m, 6H), 7.25 (d, J = 8.2 Hz,
			2H), 5.14 (s, 2H), 4.40 (d, J = 6.3 Hz, 2H).
305	15.2	5-fluoropyridine-2- carboxylic acid
			Compound 305: (4-chlorophenyl)methyl N-
			(4-{[(5-fluoropyridin-2-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 414.0 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			9.23 (t, J = 6.5 Hz, 1H), 8.68-8.62 (m, 1H),
			8.12 (dd, J = 8.8, 4.7 Hz, 1H), 7.91 (td, J = 8.6,
			4.6 Hz, 1H), 7.46 (s, 4H), 7.39 (d, J = 8.2 Hz,
			2H), 7.24 (d, J = 8.2 Hz, 2H), 5.13 (s, 2H), 4.41
			(d, J = 6.3 Hz, 2H).
109	15.2	2-methylpyrimidine-5- carboxylic acid
			Compound 109: (4-chlorophenyl)methyl N-
			(4-{[(2-methylpyrimidin-5-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-ES (POS.) m/z: 412.0 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H),
			9.27-9.22 (m, 1H), 9.09 (s, 2H), 7.51-7.38
			(m, 6H), 7.26 (d, J = 8.2 Hz, 2H), 5.14 (s, 2H),
			4.44 (d, J = 5.9 Hz, 2H), 2.68 (s, 3H).
193	15.2	1-methylpyrazole-4- carboxylic acid
			Compound 193: (4-chlorophenyl)methyl N-
			(4-{[(1-methylpyrazol-4-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-ES (POS.) m/z: 398.9 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.51 (t, J = 6.2 Hz, 1H), 8.13 (s, 1H), 7.85 (s,
			1H), 7.49-7.37 (m, 6H), 7.20 (d, J = 8.1 Hz,
			2H), 5.13 (s, 2H), 4.34 (d, J = 5.9 Hz, 2H), 3.85
			(s, 3H).
136	15.2	5-methylpyrazine-2- carboxylic acid
			Compound 136: (4-chlorophenyl)methyl N-
			(4-{[(5-methylpyrazin-2-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-ES (NEG.) m/z: 409.0 [M − H]−. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			9.33 (t, J = 6.6 Hz, 1H), 9.05 (s, 1H), 8.62 (s,
			1H), 7.48-7.43 (m, 4H), 7.39 (d, J = 8.2 Hz,
			2H), 7.24 (d, J = 8.1 Hz, 2H), 5.13 (s, 2H), 4.42
			(d, J = 6.3 Hz, 2H), 2.60 (s, 3H).
254	15.2	1-methylpyrrole-3- carboxylic acid
			Compound 254: (4-chlorophenyl)methyl N-
			(4-{[(1-methylpyrrol-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-ES (POS.) m/z: 398.0 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
			8.21 (t, J = 5.2 Hz, 1H), 7.46 (s, 4H), 7.39 (d,
			J = 8.1 Hz, 2H), 7.26 (s, 1H), 7.18 (d, J = 8.2 Hz,
			2H), 6.72-6.67 (m, 1H), 6.49-6.43 (m,
			1H), 5.13 (s, 2H), 4.31 (d, J = 5.9 Hz, 2H), 3.62
			(s, 3H).
175	15.2	pyrimidine-5- carboxylic acid
			Compound 175: (4-chlorophenyl)methyl N-
			{4-[(pyrimidin-5-
			ylformamido)methyl]phenyl}carbamate.
			LCMS-ES (POS.) m/z: 397.0 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H),
			9.37-9.30 (m, 2H), 9.20 (s, 2H), 7.50-7.36
			(m, 6H), 7.27 (d, J = 8.2 Hz, 2H), 5.14 (s, 2H),
			4.45 (d, J = 5.9 Hz, 2H).
226	15.2	pyrazinoic acid
			Compound 226: (4-chlorophenyl)methyl N-
			{4-[(pyrazin-2-
			ylformamido)methyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 397.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			9.41 (t, J = 6.0 Hz, 1H), 9.20 (s, 1H), 8.90-
			8.85 (m, 1H), 8.74 (s, 1H), 7.48-7.36 (m, 6H),
			7.25 (d, J = 8.2 Hz, 2H), 5.13 (s, 2H), 4.44 (d,
			J = 6.3 Hz, 2H).
179	15.2	3-methyloxetane-3- carboxylic acid
			Compound 179: (4-chlorophenyl)methyl N-
			(4-{[(3-methyloxetan-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 389.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			8.33-8.28 (m, 1H), 7.49-7.37 (m, 6H), 7.16
			(d, J = 8.2 Hz, 2H), 5.14 (s, 2H), 4.73 (d, J =
			5.9 Hz, 2H), 4.25 (t, J = 7.2 Hz, 4H), 1.51 (s,
			3H).
192	15.2	2-methylpyridine-3- carboxylic acid
			Compound 192: (4-chlorophenyl)methyl N-
			(4-{[(2-methylpyridin-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 410.1 [M + H]+. 1H
			NMR (400 MHz, Methanol-d4) δ 9.37 (s, 1H),
			8.52 (s, 1H), 7.93-7.86 (m, 1H), 7.49-7.36
			(m, 7H), 7.33 (d, J = 8.2 Hz, 2H), 5.18 (d, J =
			2.3 Hz, 2H), 4.52 (s, 2H), 2.62 (s, 3H). Two N—H
			hydrogens. One hydrogen exchanges with
			solvent.
165	15.2	4,6-dimethylpyridine-3- carboxylic acid
			Compound 165: 4-chlorophenyl)methyl N-
			(4-{[(4,6-dimethylpyridin-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 424.1 [M + H]+. 1H
			NMR (400 MHz, Methanol-d4) δ 8.45 (s, 1H),
			7.49-7.36 (m, 7H), 7.33 (d, J = 8.2 Hz, 2H),
			5.18 (s, 2H), 4.52 (s, 2H), 3.56-3.45 (m, 2H),
			2.58 (s, 3H), 2.48 (s, 3H).
			1H NMR (400 MHz, DMSO-d6) 8 9.77 (s, 1H),
			8.90 (s, 1H), 8.44 (d, J = 7.2 Hz, 1H), 7.50-
			7.40 (m, 6H), 7.29-7.20 (m, 3H), 5.14 (s, 2H),
			4.42-4.35 (m, 2H), 2.47 (s, 3H), 2.34 (s, 3H).
239	15.2	6- (trifluoromethyl)pyridine- 3-carboxylic acid
			Compound 239: (4-chlorophenyl)methyl N-
			[4-({[6-(trifluoromethyl)pyridin-3-
			yl]formamido}methyl)phenyl]carbamate.
			LCMS-APCI (POS.) m/z: 464.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H),
			9.41-9.36 (m, 1H), 9.18 (s, 1H), 8.49 (d, J =
			8.2 Hz, 1H), 8.06 (d, J = 8.5 Hz, 1H), 7.53-
			7.36 (m, 6H), 7.27 (d, J = 8.1 Hz, 2H), 5.14 (s,
			2H), 4.49-4.43 (m, 2H).
146	15.2	5-fluoro-6- methylpyridine-3- carboxylic acid
			Compound 146: (4-chlorophenyl)methyl N-
			(4-{[(5-fluoro-6-methylpyridin-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 428.1 [M + H]+. 1H
			NMR (400 MHz, Methanol-d4) δ 8.75 (s, 1H),
			7.96 (d, J = 10.1 Hz, 1H), 7.50-7.35 (m, 6H),
			7.31 (d, J = 8.3 Hz, 2H), 5.17 (s, 2H), 4.60 (s,
			1H), 4.54 (s, 2H), 2.57 (s, 3H). Two N-H
			hydrogens. One hydrogen exchanges with
			solvent.
157	15.2	2-methyl-1,3-oxazole- 5-carboxylic acid
			Compound 157: (4-chlorophenyl)methyl N-
			(4-{[(2-methyl-1,3-oxazol-5-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 400.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			8.97 (t, J = 5.7 Hz, 1H), 7.63 (s, 1H), 7.49-
			7.37 (m, 6H), 7.21 (d, J = 8.1 Hz, 2H), 5.13 (s,
			2H), 4.35 (d, J = 6.0 Hz, 2H), 2.47 (s, 3H).
187	15.2	1,3-oxazole-5- carboxylic acid
			Compound 187: (4-chlorophenyl)methyl N-
			{4-[(1,3-oxazol-5-
			ylformamido)methyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 386.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.78 (s, 1H),
			9.13 (t, J = 6.1 Hz, 1H), 8.57 (s, 1H), 7.80 (s,
			1H), 7.49-7.38 (m, 6H), 7.22 (d, J = 8.1 Hz,
			2H), 5.13 (s, 2H), 4.37 (d, J = 6.0 Hz, 2H).
251	15.2	3-methyl-1,2-oxazole- 4-carboxylic acid
			Compound 251: (4-chlorophenyl)methyl N-
			(4-{[(3-methyl-1,2-oxazol-4-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 400.3 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H),
			9.26 (s, 1H), 8.80 (t, J = 5.9 Hz, 1H), 7.49-
			7.39 (m, 6H), 7.23 (d, J = 8.1 Hz, 2H), 5.14 (s,
			2H), 4.35 (d, J = 5.6 Hz, 2H), 2.39 (s, 3H).
347	15.2	4-ethyl-1,3-oxazole-5- carboxylic acid
			Compound 347: (4-chlorophenyl)methyl N-
			(4-{[(4-ethyl-1,3-oxazol-5-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 414.4 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			8.91 (t, J = 6.1 Hz, 1H), 8.42 (s, 1H), 7.51-
			7.37 (m, 6H), 7.25-7.18 (m, 2H), 5.13 (s, 2H),
			4.34 (d, J = 6.2 Hz, 2H), 2.82 (q, J = 7.5 Hz,
			2H), 1.14 (t, J = 7.5 Hz, 3H).
78	15.2	3-fluoropyridine-4- carboxylic acid
			Compound 78: (4-chlorophenyl)methyl N-
			(4-{[(3-fluoropyridin-4-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 414.4 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.78 (s, 1H),
			9.13 (t, J = 5.9 Hz, 1H), 8.72-8.67 (m, 1H),
			8.53 (d, 1H), 7.61 (t, J = 5.4 Hz, 1H), 7.51-
			7.40 (m, 6H), 7.26 (d, J = 8.3 Hz, 2H), 5.14 (s,
			2H), 4.41 (d, J = 5.9 Hz, 2H).
147	15.2	3,5-difluoropyridine-4- carboxylic acid
			Compound 147: (4-chlorophenyl)methyl N-
			(4-{[15.2 (3,5-difluoropyridin-4-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-ES (POS.) m/z: 433.0 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H),
			9.43 (t, J = 5.8 Hz, 1H), 8.65 (s, 2H), 7.51-
			7.29 (m, 6H), 7.25 (d, J = 8.4 Hz, 2H), 5.15 (s,
			2H), 4.44 (d, J = 5.9 Hz, 2H).
166	15.2	2-(2- methoxyethyl)pyrazole- 3-carboxylic acid
			Compound 166: (4-chlorophenyl)methyl N-
			[4-({[2-(2-methoxyethyl)pyrazol-3-
			yl]formamido}methyl)phenyl]carbamate.
			LCMS-APCI (POS.) m/z: 443.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H),
			8.96 (s, 1H) 7.52-7.14 (m, 8H), 6.85 (s, 2H),
			5.14 (s, 2H), 4.67 (t, J = 5.4 Hz, 2H), 4.36 (d,
			J = 6.1 Hz, 2H), 3.64 (t, J = 5.6 Hz, 2H), 3.17
			(s, 3H).
327	15.2	2-cyclobutylpyrazole-3- carboxylic acid
			Compound 327: (4-chlorophenyl)methyl N-
			(4-{[(2-cyclobutylpyrazol-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-ES (POS.) m/z: 439.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H),
			8.94 (t, J = 6.0 Hz, 1H), 7.54 (s, 1H), 7.52-
			7.36 (m, 6H), 7.22 (d, J = 8.1 Hz, 2H), 6.84 (s,
			1H), 5.72-5.65 (m, 1H), 5.14 (s, 2H), 4.35 (d,
			J = 6.0 Hz, 2H), 2.32-2.26 (m, 2H), 1.85-
			1.66 (m, 4H).
203	15.2	4-fluoro-2,5- dimethylpyrazole-3- carboxylic acid
			Compound 203: (4-chlorophenyl)methyl N-
			(4-{[(4-fluoro-2,5-dimethylpyrazol-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-ES (POS.) m/z: 431.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H),
			8.60 (s, 1H), 7.49-7.21 (m, 8H), 5.14 (s, 2H),
			4.38 (d, J = 6.1 Hz, 2H), 3.87 (s, 3H), 2.14 (s,
			3H).
208	15.2	5-ethyl-2- methylpyrazole-3- carboxylic acid
			Compound 208: (4-chlorophenyl)methyl N-
			(4-{[(5-ethyl-2-methylpyrazol-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 427.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			8.87 (d, J = 6.2 Hz, 1H), 7.50-7.18 (m, 8H),
			6.69 (s, 1H), 5.14 (s, 2H), 4.34 (d, J = 5.9 Hz,
			2H), 3.98 (s, 3H), 2.57-2.52 (m, 2H), 1.16 (t,
			J = 7.6 Hz, 3H).
			1H NMR (400 MHz, Methanol-d4) δ 8.10 (s,
			1H), 7.41 (q, J = 8.2 Hz, 5H), 7.28 (d, J = 8.2 Hz,
			2H), 6.61 (s, 1H), 5.17 (s, 2H), 4.47 (d, J =
			4.9 Hz, 2H), 4.06 (s, 3H), 2.62 (q, J = 7.8 Hz,
			2H), 1.25 (t, J = 7.7 Hz, 3H). Two N—H
			hydrogens. Two hydrogens exchange with
			solvent.
302	15.2	2-(2- methylpropyl)pyrazole- 3-carboxylic acid
			Compound 302: (4-chlorophenyl)methyl N-
			[4-({[2-(2-methylpropyl)pyrazol-3-
			yl]formamido}methyl)phenyl]carbamate.
			LCMS-ES (POS.) m/z: 441.1 [M+H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			8.95 (t, J = 5.8 Hz, 1H), 7.51-7.38 (m, 7H),
			7.21 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 2.3 Hz,
			1H), 5.14 (s, 2H), 4.39-4.30 (m, 4H), 2.08
			(dt, J = 13.9, 6.8 Hz, 1H), 0.78 (d, J = 6.6 Hz,
			6H).
138	15.2	5-methoxy-2- methylpyrazole-3- carboxylic acid
			Compound 138: (4-chlorophenyl)methyl N-
			(4-{[(5-methoxy-2-methylpyrazol-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-ES (POS.) m/z: 429.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H),
			8.89 (t, J = 4.7 Hz, 1H), 7.49-7.38 (m, 6H),
			7.22 (d, J = 8.2 Hz, 2H), 6.30 (s, 1H), 5.14 (s,
			2H), 4.34 (d, J = 5.8 Hz, 2H), 3.91 (s, 3H), 3.76
			(s, 3H).
135	15.2	4-methoxy-2- methylpyrazole-3- carboxylic acid
			Compound 135: (4-chlorophenyl)methyl N-
			(4-{[(4-methoxy-2-methylpyrazol-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-ES (POS.) m/z: 429.0 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			7.86 (t, J = 5.7 Hz, 1H), 7.54-7.34 (m, 7H),
			7.23 (d, J = 7.9 Hz, 2H), 5.14 (s, 2H), 4.41 (d,
			J = 6.0 Hz, 2H), 4.00 (s, 3H), 3.84 (s, 3H).
19	15.2	trimethylpyrazole-3- carboxylic acid
			Compound 19: (4-chlorophenyl)methyl N-
			(4-{[(2,4,5-trimethylpyrazol-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 429.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H),
			8.60 (s, 1H), 7.52-7.39 (m, 6H), 7.28-7.21
			(m, 2H), 5.14 (d, J = 2.3 Hz, 2H), 4.38 (d, J =
			5.9 Hz, 2H), 3.76 (d, J = 2.2 Hz, 3H), 2.07 (d,
			J = 2.3 Hz, 3H), 2.00 (d, J = 2.2 Hz, 3H).
238	15.2	2-(oxan-4-yl)pyrazole- 3-carboxylic acid
			Compound 238: (4-chlorophenyl)methyl N-
			[4-({[2-(oxan-4-yl)pyrazol-3-
			15.2yl]formamido}methyl)phenyl]carbama
			te. LCMS-APCI (POS.) m/z: 470.3 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			8.98 (t, J = 5.4 Hz, 1H), 7.57-7.18 (m, 9H),
			6.87 (s, 1H), 5.40-5.31 (m, 1H), 5.14 (s, 2H),
			4.37 (d, J = 5.9 Hz, 2H), 3.95 (d, J = 11.5 Hz,
			2H), 3.42 (t, J = 11.9 Hz, 2H), 2.04 (dd, J =
			22.8, 11.9 Hz, 2H), 1.82 (d, J = 12.2 Hz, 2H).
124	15.2	1-methyl-2-oxo-4- piperidinecarboxylic acid
			Compound 124: (4-chlorophenyl)methyl N-
			(4-{[(1-methyl-2-oxopiperidin-4-
			yl)formamido]methyl}phenyl)carbamate.
			Example: LCMS-ES (Pos) m/z: 430 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			8.35 (d, J = 6.4 Hz, 1H), 7.43 (m, 6H), 7.15 (d,
			J = 8.1 Hz, 2H), 5.14 (s, 2H), 4.20 (m, 2H),
			3.27-3.21 (m, 2H), 2.79 (s, 3H), 2.69 (d, J =
			9.8 Hz, 1H), 2.31 (d, J = 7.8 Hz, 2H), 1.99-
			1.89 (m, 1H), 1.78 (s, 1H).
276	15.2	4-methyl-1,3-oxazole- 2-carboxylic acid
			Compound 276: (4-chlorophenyl)methyl N-
			(4-{[(4-methyl-1,3-oxazol-2-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-ES (Pos) m/z: 400 [M + H]+. 1H NMR
			(400 MHz, DMSO-d6) δ 9.76 (s, 1H), 9.37 (d,
			J = 6.6 Hz, 1H), 8.01 (s, 1H), 7.46 (d, J = 2.1 Hz,
			4H), 7.40 (d, J = 8.1 Hz, 2H), 7.22 (d, J =
			8.1 Hz, 2H), 5.13 (s, 2H), 4.33 (d, J = 6.3 Hz,
			2H), 2.16 (s, 3H).
277	15.2	4-carboxy-1- methylpyrrolidin-2-one
			Compound 277: (4-chlorophenyl)methyl N-
			(4-{[(1-methyl-5-oxopyrrolidin-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-ES (Pos) m/z: 416 [M + H]+. 1H NMR
			(400 MHz, DMSO-d6) δ 9.76 (s, 1H), 8.47 (s,
			1H), 7.50-7.38 (m, 6H), 7.16 (d, J = 8.1 Hz,
			2H), 5.14 (s, 2H), 4.21 (d, J = 5.7 Hz, 2H), 3.51
			(t, J = 9.3 Hz, 1H), 3.39-3.34 (m, 1H), 3.20-
			3.09 (m, 1H), 2.70 (s, 3H), 2.41 (d, J = 8.8 Hz,
			2H).
310	15.2	3-oxetanecarboxylic acid
			Compound 310: (4-
			chlorophenyl)methyl N-{4-[(oxetan-3-
			ylformamido)methyl]phenyl}carbamate.
			LCMS-ES (Pos) m/z: 375 [M + H]+. 1H NMR
			(400 MHz, DMSO-d6) δ 9.75 (s, 1H), 8.32 (s,
			1H), 7.43 (d, J = 28.0 Hz, 6H), 7.16 (d, J =
			8.3 Hz, 2H), 5.14 (s, 2H), 4.62 (d, J = 7.6 Hz,
			3H), 4.22 (d, J = 5.8 Hz, 2H), 3.78 (q, J = 7.4 Hz,
			1H), 3.17 (d, J = 5.2 Hz, 1H).
285	15.2	4-carboxytetrahydro- 2h-pyran
			Compound 285: (4-chlorophenyl)methyl N-
			{4-[(oxan-4-
			ylformamido)methyl]phenyl}carbamate
			LCMS-ES (Pos) m/z: 403 [M + H]+. 1H NMR
			(400 MHz, DMSO-d6) δ 9.74 (s, 1H), 8.24 (t,
			J = 6.0 Hz, 1H), 7.49-7.43 (m, 4H), 7.39 (d,
			J = 8.1 Hz, 2H), 7.14 (d, J = 8.1 Hz, 2H),
			5.14 (s, 2H), 4.19 (d, J = 5.9 Hz, 2H), 3.90-
			3.81 (m, 2H), 3.32-3.26 (m, 2H), 2.39 (p, J =
			7.7 Hz, 1H), 1.64-1.55 (m, 4H).
356	15.2	6-methyl-3- pyridinesulfonyl chloride
			Example 356: (4-chlorophenyl)methyl N-{4-
			[(6-methylpyridine-3-
			sulfonamido)methyl]phenyl}carbamate.
			LCMS-ES (Pos) m/z: 446 [M + H]+. 1H NMR
			(400 MHz, DMSO-d6) δ 9.77 (s, 1H), 8.75 (s,
			1H), 8.24 (s, 1H), 8.02-7.94 (m, 1H), 7.46 (s,
			2H), 7.42 (d, J = 8.5 Hz, 4H), 7.34 (d, J = 8.1 Hz,
			2H), 7.11 (d, J = 8.2 Hz, 1H), 5.14 (s, 2H),
			3.95 (d, J = 6.2 Hz, 2H), 2.54 (s, 3H).
76	16.2	6-ethylnicotinic acid
			Compound 76: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(6-ethylpyridin-3-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-ESI (POS.) m/z: 438.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
			8.93 (d, J = 2.3 Hz, 1H), 8.85 (d, J = 8.0 Hz,
			1H), 8.13 (dd, J = 8.1, 2.4 Hz, 1H), 7.49-7.43
			(m, 4H), 7.38 (dd, J = 12.0, 8.3 Hz, 3H), 7.29
			(d, J = 8.7 Hz, 2H), 5.13 (s, 2H), 5.10 (p, J =
			7.2 Hz, 1H), 2.80 (q, J = 7.6 Hz, 2H), 1.45
			(d, J = 7.0 Hz, 3H), 1.23 (t, J = 7.6 Hz, 3H).
110	16.2	5-methoxy-6- methylnicotinic acid
			Compound 110: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(5-methoxy-6-methylpyridin-3-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-ESI (POS.) m/z: 454.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.84 (d, J = 8.0 Hz, 1H), 8.51 (d, J = 1.8 Hz,
			1H), 7.68 (d, J = 1.8 Hz, 1H), 7.48-7.43 (m,
			4H), 7.40 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.6 Hz,
			2H), 5.17-5.09 (m, 3H), 3.87 (s, 3H),
			2.40 (s, 3H), 1.47 (d, J = 7.0 Hz, 3H).
181	16.2	1-isopropyl-1H- pyrazole-5-carboxylic acid
			Compound 181: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(2-isopropylpyrazol-3-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-ESI (POS.) m/z: 441.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
			8.54 (d, J = 8.1 Hz, 1H), 7.98 (s, 1H), 7.63
			(d, J = 1.0 Hz, 1H), 7.48-7.43 (m, 4H), 7.39
			(d, J = 8.3 Hz, 2H), 7.27 (d, J = 8.6 Hz, 2H),
			5.17 (sept, J = 6.8 Hz, 1H), 5.13 (s, 2H), 5.04
			(p, J = 7.1 Hz, 1H), 1.41 (d, J = 7.0 Hz, 3H),
			1.38 (d, J = 6.7 Hz, 3H), 1.36 (d, J = 6.7 Hz,
			3H).
290	16.2	4-cyclopropyloxazole- 5-carboxylic acid
			Compound 290: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(4-cyclopropyl-1,3-oxazol-5-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 440.3 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
			8.69 (d, J = 8.3 Hz, 1H), 8.35 (d, J = 0.6 Hz,
			1H), 7.48-7.42 (m, 4H), 7.39 (d, J = 8.4 Hz,
			2H), 7.29 (d, J = 8.7 Hz, 2H), 5.13 (s, 2H),
			5.08 (p, J = 7.1 Hz, 1H), 2.58 (ddd, J = 10.0,
			8.5, 4.9 Hz, 1H), 1.44 (d, J = 7.0 Hz, 3H), 0.98-
			0.88 (m, 2H), 0.86-0.76 (m, 2H).
259	16.2	3-(difluoromethyl)-1- methyl-1H-pyrazole-5- carboxylic acid
			Compound 259: (4-chlorophenyl)methyl N-
			[4-({[5-(difluoromethyl)-2-methylpyrazol-
			3-yl]formamido}methyl)phenyl]carbamate.
			LCMS-APCI (POS.) m/z: 463.3 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.87 (d, J = 8.1 Hz, 1H), 7.48-7.42(m, 4H),
			7.40 (d, J = 8.3 Hz, 2H), 7.28 (d, J = 8.7, 2H),
			7.24 (s, 1H), 7.02 (t, J = 54.7, 1H), 5.13 (s,
			2H), 5.06 (p, J = 7.0 Hz, 1H), 4.05 (s, 3H),
			1.43 (d, J = 7.0 Hz, 3H).
100	16.2	6-methoxynicotinic acid
			Compound 100: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(6-methoxypyridin-3-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 440.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.73 (d, J = 8.0 Hz, 1H), 8.68 (s, 1H), 8.14
			(d, J = 8.9 Hz, 1H), 7.49-7.42 (m, 4H), 7.39
			(d, J = 8.3 Hz, 2H), 7.29 (d, J = 8.2 Hz, 2H),
			6.88 (d, J = 8.6 Hz, 1H), 5.15-5.05 (m, 3H),
			3.90 (s, 3H), 1.44 (d, J = 7.0 Hz, 3H).
213	16.2	2-methoxy-6- methylnicotinic acid
			Compound 213: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(2-methoxy-6-methylpyridin-3-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 454.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			8.37 (d, J = 7.9 Hz, 1H), 7.97 (d, J = 7.6 Hz,
			1H), 7.48-7.44 (m, 4H), 7.41 (d, J = 8.4 Hz,
			2H), 7.30 (d, J = 8.2 Hz, 2H), 6.96 (d, J = 7.6 Hz,
			1H), 5.13 (s, 2H), 5.06 (p, J = 7.1 Hz, 1H),
			3.96 (s, 3H), 2.43 (s, 3H), 1.43 (d, J = 6.9 Hz,
			3H).
218	16.2	2-methyl-1,3-oxazole- 5-carboxylic acid
			Compound 218: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(2-methyl-1,3-oxazol-5-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 414.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.78 (d, J = 8.0 Hz, 1H), 7.67-7.62 (m, 1H),
			7.51-7.34 (m, 6H), 7.28 (d, J = 7.7 Hz, 2H),
			5.13 (s, 2H), 5.06 (t, J = 7.2 Hz, 1H), 2.47 (s,
			3H), 1.43 (d, J = 7.0 Hz, 3H).
149	16.2	2-methylpyrazole-3- carboxylic acid
			Compound 149: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(2-methylpyrazol-3-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 413.4 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) 8 9.75 (s, 1H),
			8.71 (d, J = 8.1 Hz, 1H), 7.48-7.37 (m, 7H),
			7.28 (d, J = 7.7 Hz, 2H), 6.95 (s, 1H), 5.13 (s,
			2H), 5.10-5.03 (m, 1H), 4.01 (s, 3H), 1.44 (d,
			3H).
159	16.2	5-fluoropyridine-3- carboxylic acid
			Compound 159: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(5-fluoropyridin-3-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 428.3 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			9.02 (d, J = 7.9 Hz, 1H), 8.91 (s, 1H), 8.74 (s,
			1H), 8.12 (d, J = 9.7 Hz, 1H), 7.48-7.38 (m,
			6H), 7.31 (d, J = 8.3 Hz, 2H), 5.14 (s, 2H), 5.13-
			5.08 (m, 1H), 1.47 (d, J = 7.0 Hz, 3H).
150	16.2	3-methyl-1,2-oxazole- 4-carboxylic acid
			Compound 150: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(3-methyl-1,2-oxazol-4-
			16.2yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 414.4 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			9.32 (s, 1H), 8.62 (d, J = 7.9 Hz, 1H), 7.51-
			7.38 (m, 6H), 7.31-7.24 (m, 2H), 5.14 (s, 2H),
			5.03 (p, J = 7.1 Hz, 1H), 2.35 (s, 3H), 1.42 (d,
			J = 7.0 Hz, 3H).
241	16.2	5-methyl-1,3-oxazole- 4-carboxylic acid
			Compound 241: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(5-methyl-1,3-oxazol-4-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-ES (POS.) m/z: 415.0 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
			8.37-8.29 (m, 2H), 7.51-7.35 (m, 6H), 7.34-
			7.26 (m, 2H), 5.13 (s, 2H), 5.05 (p, J = 7.3 Hz,
			1H), 2.54 (s, 3H), 1.45 (d, J = 7.1 Hz, 3H).
260	16.2	4-ethyl-1,3-oxazole-5- carboxylic acid
			Compound 260: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(4-ethyl-1,3-oxazol-5-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-ES (POS.) m/z: 428.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.74 (d, J = 8.3 Hz, 1H), 8.42 (s, 1H), 7.51-
			7.36 (m, 6H), 7.33-7.25 (m, 2H), 5.13 (s, 2H),
			5.06 (p, J = 7.2 Hz, 1H), 2.79 (q, J = 7.5 Hz,
			2H), 1.44 (d, J = 7.0 Hz, 3H), 1.12 (t, J = 7.5 Hz,
			3H).
152	16.2	4-methyl-1,3-oxazole- 5-carboxylic acid
			Compound 152: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(4-methyl-1,3-oxazol-5-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 414.3 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.74 (d, J = 8.3 Hz, 1H), 8.42 (s, 1H), 7.48-
			7.43 (m, 4H), 7.39 (d, J = 8.3 Hz, 2H), 7.33-
			7.25 (m, 2H), 5.13 (s, 2H), 5.06 (p, J = 7.3 Hz,
			1H), 2.34 (s, 3H), 1.44 (d, J = 7.1 Hz, 3H).
142	16.2	4-methyl-1,2-oxazole- 5-carboxylic acid
			Compound 142: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(4-methyl-1,2-oxazol-5-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 414.4 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.74 (d, J = 8.3 Hz, 1H), 8.42 (s, 1H), 7.48-
			7.43 (m, 4H), 7.39 (d, J = 8.3 Hz, 2H), 7.33-
			7.25 (m, 2H), 5.13 (s, 2H), 5.06 (p, J = 7.3 Hz,
			1H), 2.34 (s, 3H), 1.44 (d, J = 7.1 Hz, 3H).
44	16.2	3-fluoropyridine-4- carboxylic acid
			Compound 44: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(3-fluoropyridin-4-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 428.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H),
			9.05 (d, J = 7.9 Hz, 1H), 8.68 (d, J = 1.5 Hz,
			1H), 8.52 (dd, J = 4.8, 1.2 Hz, 1H), 7.55 (t, J =
			5.9, 4.8 Hz, 1H), 7.51-7.39 (m, 6H), 7.34-
			7.26 (m, 2H), 5.14 (s, 2H), 5.07 (p, J = 7.1 Hz,
			1H), 1.42 (d, J = 7.0 Hz, 3H).
57	16.2	3,5-difluoropyridine-4- carboxylic acid
			Compound 57: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(3,5-difluoropyridin-4-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 446.3 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.79 (s, 1H),
			9.37 (d, J = 7.9 Hz, 1H), 8.64 (s, 2H), 7.49-
			7.38 (m, 7H), 7.28 (d, J = 8.4 Hz, 2H), 5.15 (s,
			2H), 1.41 (d, J = 6.9 Hz, 3H).
56	16.2	2-(2- methoxyethyl)pyrazole- 3-carboxylic acid
			Compound 56: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-{[2-(2-methoxyethyl)pyrazol-3-
			yl]formamido}ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 457.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			8.75 (d, J = 8.2 Hz, 1H), 7.51-7.23 (m, 9H),
			6.89 (s, 1H), 5.14 (s, 2H), 5.10-5.02 (m, 1H),
			4.61 (d, J = 5.7 Hz, 2H), 3.60 (t, J = 5.8 Hz,
			2H), 3.14 (s, 3H), 1.44 (d, J = 6.8 Hz, 3H).
210	16.2	2-cyclobutylpyrazole-3- carboxylic acid
			Compound 210: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(2-cyclobutylpyrazol-3-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-ES (POS.) m/z: 453.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			8.72 (d, J = 8.2 Hz, 1H), 7.53 (s, 1H), 7.48-
			7.37 (m, 6H), 7.27 (d, J = 8.2 Hz, 2H), 6.89 (s,
			1H), 5.62-5.55 (m, 1H), 5.14 (s, 2H), 5.09-
			5.00 (m, 1H), 2.27 (s, 2H), 1.78-1.70 (m, 2H),
			1.43 (d, J = 6.9 Hz, 3H), 1.01 (s, 2H).
141	16.2	4-fluoro-2,5- dimethylpyrazole-3- carboxylic acid
			Compound 141: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(4-fluoro-2,5-dimethylpyrazol-
			3-yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 445.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			8.52 (d, J = 8.0 Hz, 1H), 7.49-7.37 (m, 6H),
			7.29 (d, J = 8.0 Hz, 2H), 5.14 (s, 2H), 5.06 (p,
			J = 7.2 Hz, 1H), 3.81 (s, 3H), 2.14 (s, 3H), 1.43
			(d, J = 6.9 Hz, 3H).
137	16.2	5-ethyl-2- methylpyrazole-3- carboxylic acid
			Compound 137: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(5-ethyl-2-methylpyrazol-3-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 441.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.64 (d, J = 8.1 Hz, 1H), 7.48-7.37 (m, 6H),
			7.28 (d, J = 8.2 Hz, 2H), 6.77 (s, 1H), 5.14 (s,
			2H), 5.05 (t, J = 7.3 Hz, 1H), 3.94 (s, 3H), 2.56
			(d, J = 7.8 Hz, 2H), 1.42 (d, J = 7.0 Hz, 3H),
			1.17 (t, J = 8.4, 6.8 Hz, 3H).
129	16.2	2-(2- methylpropyl)pyrazole-
			Compound 129: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-{[2-(2-methylpropyl)pyrazol-3-
			yl]formamido}ethyl]phenyl}carbamate.
			LCMS-ES (POS.) m/z: 455.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.73 (d, J = 8.2 Hz, 1H), 7.50-7.22 (m, 9H),
			6.91 (s, 1H), 5.14 (s, 2H), 5.10-5.02 (m, 1H),
			4.35-4.22 (m, 2H), 2.07-1.99 (m, 1H), 1.43
			(d, J = 7.1 Hz, 3H), 0.75 (t, J = 7.4 Hz, 6H).
95	16.2	3-carboxylic acid 5-methoxy-2- methylpyrazole-3- carboxylic acid
			Compound 95: (4-chlorophenyl)methyl N-
			(4-[(1S)-1-[(5-methoxy-2-methylpyrazol-3-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 443.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			8.65 (d, J = 8.3 Hz, 1H), 7.51-7.34 (m, 6H),
			7.27 (d, J = 8.2 Hz, 2H), 6.38 (s, 1H), 5.14 (s,
			2H), 5.04 (t, J = 7.5 Hz, 1H), 3.87 (s, 3H), 3.77
			(s, 3H), 1.42 (d, J = 7.1 Hz, 3H).
92	16.2	4-methoxy-2- methylpyrazole-3- carboxylic acid
			Compound 92: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(4-methoxy-2-methylpyrazol-3-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 443.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H),
			7.56 (d, J = 7.9 Hz, 1H), 7.49-7.39 (m, 7H),
			7.29 (d, J = 8.0 Hz, 2H), 5.14 (s, 2H), 5.06
			(t, J = 7.2 Hz, 1H), 3.96 (s, 3H), 3.87 (s, 3H),
			1.44 (d, J = 7.0 Hz, 3H).
12	16.2	trimethylpyrazole-3- carboxylic acid
			Compound 12: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(2,4,5-trimethylpyrazol-3-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 441.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H),
			8.57 (d, J = 8.3 Hz, 1H), 7.49-7.38 (m, 6H),
			7.33-7.26 (m, 2H), 5.14 (s, 2H), 5.06 (p, J =
			7.4, 6.8 Hz, 1H), 3.71 (s, 3H), 2.07 (s, 3H),
			1.98 (s, 3H), 1.42 (d, J = 6.9 Hz, 3H).
20	16.2	2-(oxan-4-yl)pyrazole- 3-carboxylic acid
			Compound 20: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-{[2-(oxan-4-yl)pyrazol-3-
			yl]formamido}ethyl]phenyl}carbamate.
			LCMS-ES (POS.) m/z: 483.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			8.79-8.72 (m, 1H), 7.55-7.49 (m, 1H), 7.49-
			7.37 (m, 6H), 7.32-7.24 (m, 2H), 6.93 (s,
			1H), 5.29-5.21 (m, 1H), 5.14 (s, 2H), 5.10-
			5.03 (m, 1H), 3.93 (s, 2H), 3.44-3.35 (m, 2H),
			2.02 (q, J = 12.6 Hz, 2H), 1.80 (t, J = 12.2 Hz,
			2H), 1.44 (d, J = 6.8 Hz, 3H).
			1H NMR (400 MHz, Methylene Chloride-d2)
			δ 7.52 (s, 1H), 7.45-7.31 (m, 8H), 6.82 (s,
			1H), 6.56 (s, 1H), 6.28 (d, J = 7.4 Hz, 1H),
			5.34-5.28 (m, 1H), 5.22-5.17 (m, 3H),
			4.11-4.01 (m, 2H), 3.54 (q, J = 11.2 Hz,
			2H), 2.31-2.18 (m, 2H), 1.93 (d, J = 13.1 Hz,
			2H), 1.58 (d, J = 7.1 Hz, 3H).
164	16.2	6- (difluoromethyl)nicotinic acid
			Compound 164: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-{[6-(difluoromethyl)pyridin-3-
			yl]formamido}ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 460.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			9.11-9.05 (m, 2H), 8.39 (d, J = 8.2 Hz, 1H),
			7.81 (d, J = 8.2 Hz, 1H), 7.48-7.43 (m, 4H),
			7.41 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz,
			2H), 7.03 (t, J = 54.6 Hz, 1H), 5.17-5.08 (m,
			1H), 5.13 (s, 2H), 1.47 (d, J = 7.0 Hz, 3H).
163	16.2	6-isopropylnicotinic acid
			Compound 163: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(6-isopropylpyridin-3-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 452.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
			8.93 (s, 1H), 8.85 (d, J = 8.1 Hz, 1H), 8.15
			(d, J = 8.2 Hz, 1H), 7.48-7.43 (m, 4H), 7.42-
			7.37 (m, 3H), 7.29 (d, J = 8.4 Hz, 2H), 5.16-
			5.07 (m, 3H), 3.08 (p, J = 6.9 Hz, 1H), 1.45
			(d, J = 7.0 Hz, 3H), 1.25 (s, 3H), 1.23 (s, 3H).
60	16.2	6-methylpyridine-3- carboxylic acid
			Compound 60: 4-chlorobenzyl (S)-(4-(1-(6-
			methylnicotinamido)ethyl)phenyl)carbamate.
			LCMS- APCI (POS.) m/z: 424.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.93 (d, J = 2.1 Hz, 1H), 8.89 (d, J = 8.0 Hz,
			1H), 8.18 (d, J = 8.2 Hz, 1H), 7.45 (s, 3H), 7.44-
			7.37 (m, 3H), 7.30 (d, J = 8.3 Hz, 2H), 5.13
			(s, 2H), 2.54 (s, 3H), 1.45 (d, J = 7.0 Hz, 3H),
			1.26 (t, J = 6.0 Hz, 2H).
117	16.2	tetrahydro-2H-pyran-4- carboxylic acid
			Compound 117: 4-chlorobenzyl (S)-(4-(1-
			(tetrahydro-2H-pyran-4-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS- APCI (POS.) m/z: 417.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.72 (s, 1H),
			8.13 (d, J = 8.0 Hz, 1H), 7.45 (s, 4H), 7.37 (d,
			J = 8.2 Hz, 2H), 7.21-7.16 (m, 2H), 5.13 (d,
			J = 1.9 Hz, 2H), 4.83 (p, J = 7.2 Hz, 1H), 3.85
			(dd, J = 10.4, 5.0 Hz, 2H), 3.26 (dd, J = 10.9,
			3.8 Hz, 2H), 1.55 (pd, J = 10.7, 4.3 Hz, 5H),
			1.29 (d, J = 7.0 Hz, 3H).
122	16.2	oxetane-3-carboxylic acid
			Compound 122: 4-chlorobenzyl (S)-(4-(1-
			(oxetane-3-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS- APCI (POS.) m/z: 389.0 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
			8.23 (d, J = 8.0 Hz, 1H), 7.45 (s, 4H), 7.38 (d,
			J = 8.2 Hz, 2H), 7.19 (d, J = 8.3 Hz, 2H), 5.13
			(s, 2H), 4.88 (t, J = 7.2 Hz, 1H), 4.63-4.57
			(m, 2H), 4.54 (t, J = 6.2 Hz, 1H), 3.79-3.70
			(m, 1H), 3.38 (q, J = 7.0 Hz, 1H), 1.30 (d, J =
			7.0 Hz, 3H), 1.09 (t, J = 7.1 Hz, 1H).
189	16.2	3-methyloxetane-3- carboxylic acid
			Compound 189: 4-chlorobenzyl (S)-(4-(1-
			(3-methyloxetane-3-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS- APCI (POS.) m/z: 403.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
			8.13 (d, J = 7.9 Hz, 1H), 7.45 (s, 4H), 7.39 (d,
			J = 8.2 Hz, 2H), 7.20 (d, J = 8.1 Hz, 2H), 5.13
			(s, 2H), 4.88 (t, J = 7.3 Hz, 1H), 4.69 (d, J =
			6.0 Hz, 2H), 4.24 (t, J = 4.9 Hz, 2H), 1.48 (s,
			3H), 1.33 (d, J = 7.0 Hz, 3H).
246	16.2	oxazole-5-carboxylic acid
			Compound 246: 4-chlorobenzyl (S)-(4-(1-
			(oxazole-5-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS- APCI (POS.) m/z: 400.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			8.94 (d, J = 8.2 Hz, 1H), 8.55 (s, 1H), 7.80 (s,
			1H), 7.45 (s, 4H), 7.40 (d, J = 8.3 Hz, 2H),
			7.28 (d, J = 8.2 Hz, 2H), 5.13 (s, 2H), 5.06 (t,
			J = 7.5 Hz, 1H), 1.43 (d, J = 7.0 Hz, 3H).
125	16.2	2,4-dimethyloxazole-5- carboxylic acid
			Compound 125: 4-chlorobenzyl (S)-(4-(1-
			(2,4-dimethyloxazole-5-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS- APCI (POS.) m/z: 428.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.58 (d, J = 8.3 Hz, 1H), 7.45 (s, 4H), 7.38 (d,
			J = 8.2 Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H), 5.12
			(s, 2H), 5.03 (t, J = 7.5 Hz, 1H), 2.43 (s, 3H),
			2.27 (s, 3H), 1.42 (d, J = 7.1 Hz, 3H).
46	16.2	3,4-dimethylisoxazole- 5-carboxylic acid
			Compound 46: 4-chlorobenzyl (S)-(4-(1-
			(3,4-dimethylisoxazole-5-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS- APCI (POS.) m/z: 428.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.77 (s,
			1H), 8.38 (d, J = 8.0 Hz, 1H), 7.45 (s, 4H), 7.41
			(d, J = 9.0 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H),
			5.13 (s, 2H), 5.02 (t, J = 7.3 Hz, 1H), 2.46 (s,
			3H), 2.25 (s, 3H), 1.40 (d, J = 7.0 Hz, 3H).
200	16.2	3-methylisoxazole-5- carboxylic acid
			Compound 200: 4-chlorobenzyl (S)-(4-(1-
			(3-methylisoxazole-5-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS- APCI (POS.) m/z: 414.0 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.76 (s,
			1H), 9.22 (d, J = 8.5 Hz, 1H), 7.45 (s, 4H), 7.40
			(d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H),
			6.93 (s, 1H), 5.13 (s, 2H), 5.05 (t, J = 7.2 Hz,
			1H), 2.28 (s, 3H), 1.44 (d, J = 6.9 Hz, 3H).
267	16.2	5-methyloxazole-2- carboxylic acid
			Compound 267: 4-chlorobenzyl (S)-(4-(1-
			(5-methyloxazole-2-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS- APCI (POS.) m/z: 414.0 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
			9.11 (d, J = 8.5 Hz, 1H), 7.45 (d, J = 2.3 Hz,
			4H), 7.38 (d, J = 8.2 Hz, 2H), 7.29 (d, J = 8.2 Hz,
			2H), 7.06 (s, 1H), 5.13 (s, 2H), 5.04 (t, J =
			7.5 Hz, 1H), 2.36 (s, 3H), 1.44 (d, J = 7.0 Hz,
			3H).
224	16.2	2-(oxazol-2-yl)acetic acid
			Compound 224: 4-chlorobenzyl (S)-(4-(1-
			(2-(oxazol-2-
			yl)acetamido)ethyl)phenyl)carbamate.
			LCMS- APCI (POS.) m/z: 414.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.59 (d, J = 7.9 Hz, 1H), 8.01 (s, 1H), 7.45 (s,
			4H), 7.39 (d, J = 8.1 Hz, 2H), 7.22 (d, J = 8.2 Hz,
			2H), 7.12 (s, 1H), 5.13 (s, 2H), 4.87-4.81
			(m, 1H), 3.71 (s, 2H), 1.34 (d, J = 7.1 Hz, 3H).
243	16.2	4-methyloxazole-2- carboxylic acid
			Compound 243: 4-chlorobenzyl (S)-(4-(1-
			(4-methyloxazole-2-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS- APCI (POS.) m/z: 414.0 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
			9.20 (d, J = 8.4 Hz, 1H), 7.99 (s, 1H), 7.45 (s,
			4H), 7.38 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.3
			Hz, 2H), 5.12 (s, 2H), 5.06-5.00 (m, 1H),
			2.16 (s, 3H), 1.44 (d, J = 7.0 Hz, 3H).
206	17.2	3,5-dimethyl-1H- pyrazole-4-carboxylic acid
			Compound 206: (4-chlorophenyl)methyl N-
			(4-{[1-(3,5-dimethyl-1H-pyrazol-4-yl)-N-
			methylformamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 427.3 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 12.44 (bs,
			1H), 9.80 (s, 1H), 7.50-7.39 (m, 6H), 7.14
			(bs, 2H), 5.13 (s, 2H), 4.49 (bs, 2H), 2.77 (s,
			3H), 2.12 (s, 6H).
71	17.2	4-fluoro-1H-pyrazole-3- carboxylic acid
			Compound 71: (4-chlorophenyl)methyl N-
			(4-{[1-(4-fluoro-1H-pyrazol-3-yl)-N-
			methylformamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 417.3 [M + H]+.
			1H NMR (400 MHz, 80° C., DMSO-d6) δ 12.93
			(s, 1H), 9.52 (s, 1H), 7.83 (bs, 1H), 7.52-7.33
			(m, 6H), 7.25-7.12 (m, 2H), 5.15 (s, 2H), 4.64
			(bs, 2H), 2.95 (bs, 3H).
91	17.2	1H-pyrazole-5- carboxylic acid
			Compound 91: (4-chlorophenyl)methyl N-
			{4-[(N-methyl-1-2H-pyrazol-3-
			ylformamido)methyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 399.3 [M + H]+. 1H
			NMR (400 MHz, 80° C., DMSO-d6) δ 12.95
			(bs, 1H), 9.50 (s, 1H), 7.72 (s, 1H), 7.47-
			7.39 (m, 6H), 7.19 (d, J = 8.1 Hz, 2H), 6.58
			(s, 1H), 5.15 (s, 2H), 4.69 (bs, 2H), 3.00 (bs,
			3H).
85	17.2	2-methyl-1,3-oxazole- 5-carboxylic acid
			Compound 85: (4-chlorophenyl)methyl N-
			(4-{[N-methyl-1-(2-methyl-1,3-oxazol-5-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 414.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6, temperature =
			354 K) δ 9.54 (s, 1H), 7.50 (s, 1H), 7.47-7.42
			(m, 6H), 7.19 (d, J = 8.1 Hz, 2H), 5.16 (s, 2H),
			4.64 (s, 2H), 3.05 (s, 3H), 2.47 (s, 3H).
50	17.2	2-methylpyrazole-3- carboxylic acid
			Compound 50: (4-chlorophenyl)methyl N-
			(4-{[N-methyl-1-(2-methylpyrazol-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 413.3 [M + H]+ . . 1H
			NMR (400 MHz, DMSO-d6) δ 9.82 (s, 1H),
			7.49-7.44 (m, 6H), 7.28-7.23 (m, 1H), 7.10-
			7.05 (m, 1H), 6.56 (s, 1H), 6.37 (s, 1H), 5.15
			(s, 2H), 4.57 (d, J = 26.7 Hz, 2H), 3.84 (d, J =
			16.7 Hz, 3H), 2.93 (s, 3H).
250	17.2	5-fluoropyridine-3- carboxylic acid
			Compound 250: (4-chlorophenyl)methyl N-
			(4-{[1-(5-fluoropyridin-3-yl)-N-
			methylformamido]methyl}phenyl)carbamate.
			LCMS-ES (POS.) m/z: 428.0 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6, temp = 354 K) δ
			9.55 (s, 1H), 8.63 (s, 1H), 8.52 (s, 1H), 7.81 (d,
			J = 9.3 Hz, 1H), 7.51-7.42 (m, 6H), 7.22 (s,
			2H), 5.16 (s, 2H), 4.55 (s, 2H), 2.89 (s, 3H).
108	17.2	3-methyl-1,2-oxazole- 4-carboxylic acid
			Compound 108: (4-chlorophenyl)methyl N-
			(4-{[N-methyl-1-(3-methyl-1,2-oxazol-4-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 414.3 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6 temp = 354 K) δ
			9.54 (s, 1H), 9.04 (s, 1H), 7.51-7.42 (m, 6H),
			7.18 (d, J = 8.1 Hz, 2H), 5.16 (s, 2H), 4.58 (s,
			2H), 2.96 (s, 3H), 2.30 (s, 3H).
340	17.2	5-methyl-1,3-oxazole- 4-carboxylic acid
			Compound 340: (4-chlorophenyl)methyl N-
			(4-{[N-methyl-1-(5-methyl-1,3-oxazol-4-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 414.8 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6 temp = 354 K) δ
			9.51 (s, 1H), 8.21 (s, 1H), 7.46-7.40 (m, 6H),
			7.19 (d, J = 8.2 Hz, 2H), 5.16 (s, 2H), 4.72 (bs,
			2H), 3.00 (bs, 3H), 2.48 (s, 3H).
176	17.2	4-ethyl-1,3-oxazole-5- carboxylic acid
			Compound 176: (4-chlorophenyl)methyl N-
			(4-{[1-(4-ethyl-1,3-oxazol-5-yl)-N-
			methylformamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 428.3 [M + H]+.
			1H NMR (400 MHz, DMSO-d6, temp = 354 K)
			δ 9.53 (s, 1H), 8.28 (s, 1H), 7.49-7.42 (m,
			6H), 7.19 (d, J = 8.2 Hz, 2H), 5.16 (s, 2H), 4.59
			(s, 2H), 2.97 (s, 3H), 2.71 (q, J = 7.5 Hz, 2H),
			1.18 (t, J = 7.5 Hz, 3H).
36	17.2	3-fluoropyridine-4- carboxylic acid
			Compound 36: (4-chlorophenyl)methyl N-
			(4-{[1-(3-fluoropyridin-4-yl)-N-
			methylformamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 428.3 [M + H]+.
			1H NMR (400 MHz, DMSO-d6, temp = 354 K)
			δ 9.56 (s, 1H), 8.69-8.64 (m, 1H), 8.52 (d, J =
			13.6 Hz, 1H), 7.52-7.43 (m, 7H), 7.27 (d, J =
			7.9 Hz, 1H), 7.07 (d, J = 8.1 Hz, 1H), 5.16
			(s, 2H), 4.66 (s, 1H), 4.33 (s, 1H), 2.95 (s, 1H),
			2.77 (s, 2H).
			NB: rotamers observed. 4.66 and 4.33 are a
			methylene group with 2H, 2.95 and 2.77 are
			the N-methyl group with 3H.
55	17.2	3,5-difluoropyridine-4- carboxylic acid
			Compound 55: (4-chlorophenyl)methyl N-
			(4-{[1-(3,5-difluoropyridin-4-yl)-N-
			methylformamido]methyl}phenyl)carbamate.
			LCMS-ES (POS.) m/z: 446.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.58 (s, 1H),
			8.62 (d, J = 14.5 Hz, 2H), 7.52-7.42 (m, 6H),
			7.26 (d, J = 8.1 Hz, 1H), 7.05 (d, J = 8.1 Hz,
			1H), 5.19-5.13 (m, 2H), 4.68 (s, 1H), 4.38 (s,
			1H), 2.99 (s, 1H), 2.81 (s, 2H).
			NB: Rotamers observed. Peaks at 2.99 and
			2.81 together make up the N-methyl group.
131	17.2	2-isopropylpyrazole-3- carboxylic acid
			Compound 131: (4-chlorophenyl)methyl N-
			(4-{[1-(2-isopropylpyrazol-3-yl)-N-
			methylformamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 441.3 [M + H]+.
			1H NMR (400 MHz, DMSO-d6, temp = 353 K)
			δ 9.56 (s, 1H), 7.51-7.40 (m, 7H), 7.18 (s,
			2H), 6.38 (s, 1H), 5.16 (s, 2H), 4.67 (p, J =
			6.6 Hz, 1H), 4.58 (s, 2H), 2.92 (s, 3H), 1.40 (d,
			J = 6.7 Hz, 6H).
77	17.2	2-(2- methoxyethyl)pyrazole- 3-carboxylic acid
			Compound 77: (4-chlorophenyl)methyl N-
			[4-({1-[2-(2-methoxyethyl)pyrazol-3-yl]-N-
			methylformamido}methyl)phenyl]carbamate.
			LCMS-APCI (POS.) m/z: 457.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.81 (s, 1H),
			7.54-7.43 (m, 6H), 7.26 (d, J = 8.0 Hz, 1H),
			7.18-7.12 (m, 1H), 6.54 (s, 2H), 5.15 (s, 2H),
			4.56 (d, J = 31.0 Hz, 2H), 4.39 (s, 2H), 3.65-
			3.55 (m, 2H), 3.15 (d, J = 37.7 Hz, 3H), 2.91
			(s, 3H). Rotamers observed.
74	17.2	2-cyclobutylpyrazole-3- carboxylic acid
			Compound 74: (4-chlorophenyl)methyl N-
			(4-{[1-(2-cyclobutylpyrazol-3-yl)-N-
			methylformamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 453.2 [M + H]+.
			1H NMR (400 MHz, DMSO-d6, temp = 353 K)
			δ 9.55 (s, 1H), 7.53-7.42 (m, 7H), 7.17 (s,
			2H), 6.41 (s, 1H), 5.16 (s, 2H), 4.94-4.85 (m,
			1H), 4.55 (s, 2H), 2.90 (s, 3H), 2.61-2.52 (m,
			2H), 2.36-2.26 (m, 2H), 1.80 (q, J = 9.3 Hz,
			2H).
188	17.2	4-fluoro-2,5- dimethylpyrazole-3- carboxylic acid
			Compound 188: (4-chlorophenyl)methyl N-
			(4-{[1-(4-fluoro-2,5-dimethylpyrazol-3-yl)-
			N-
			methylformamido]methyl}phenyl)carbamate.
			LCMS-ES (POS.) m/z: 445.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6, temp = 353 K) δ
			9.55 (s, 1H), 7.50-7.42 (m, 5H), 7.27-7.08
			(m, 3H), 5.16 (s, 2H), 4.58 (s, 2H), 3.72 (s,
			3H), 2.93 (s, 3H), 2.15 (s, 3H).
289	17.2	5-ethyl-2- methylpyrazole-3- carboxylic acid
			Compound 289: (4-chlorophenyl)methyl N-
			(4-{[1-(5-ethyl-2-methylpyrazol-3-yl)-N-
			methylformamido]methyl}phenyl)carbamate.
			LCMS-ES (POS.) m/z: 441.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6, temp = 354 K) δ
			9.55 (s, 1H), 7.50-7.42 (m, 6H), 7.22-7.13
			(m, 2H), 6.24 (s, 1H), 5.16 (s, 2H), 4.58 (s,
			2H), 3.77 (s, 3H), 2.94 (s, 3H), 2.60-2.54 (m,
			2H), 1.17 (t, J = 7.6 Hz, 3H).
94	17.2	2-(2- methylpropyl)pyrazole- 3-carboxylic acid
			Compound 94: (4-chlorophenyl)methyl N-
			[4-({N-methyl-1-[2-(2-
			methylpropyl)pyrazol-3-
			yl]formamido}methyl)phenyl]carbamate.
			LCMS-ES (POS.) m/z: 455.1 [M + H]+. . 1H
			NMR (400 MHz, DMSO-d6) δ 9.55 (s, 1H),
			7.50-7.42 (m, 7H), 7.24-7.19 (m, 2H), 6.44
			(s, 1H), 5.16 (s, 2H), 4.59 (s, 2H), 4.02 (d, J =
			7.1 Hz, 2H), 2.93 (s, 3H), 2.14-2.01 (m, 1H),
			0.82 (d, J = 6.7 Hz, 6H).
90	17.2	5-methoxy-2- methylpyrazole-3- carboxylic acid
			Compound 90: (4-chlorophenyl)methyl N-
			(4-{[1-(5-methoxy-2-methylpyrazol-3-yl)-
			N-
			methylformamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 443.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6, temp = 353 K)
			δ 9.55 (s, 1H), 7.50-7.42 (m, 6H), 7.18 (s,
			2H), 5.87 (s, 1H), 5.16 (s, 2H), 4.58 (s, 2H),
			3.78 (s, 3H), 3.68 (s, 3H), 2.93 (s, 3H).
253	17.2	4-methoxy-2- methylpyrazole-3- carboxylic acid
			Compound 253: (4-chlorophenyl)methyl N-
			(4-{[1-(4-methoxy-2-methylpyrazol-3-yl)-
			N-
			methylformamido]methyl}phenyl)carbamate.
			LCMS-ES (POS.) m/z: 443.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6, temp = 344 K) δ
			9.59 (s, 1H), 7.49-6.99 (m, 9H), 5.16 (s, 2H),
			3.86-3.68 (m, 6H), 3.20 (s, 2H), 2.89 (s, 3H).
127	17.2	trimethylpyrazole-3- carboxylic acid
			Compound 127: (4-chlorophenyl)methyl N-
			(4-{[N-methyl-1-(2,4,5-trimethylpyrazol-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 441.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6, temp = 343 K) δ
			9.61 (s, 1H), 7.53-6.96 (m, 8H), 5.16 (s, 2H),
			4.56 (s, 2H), 3.63 (s, 3H), 2.92-2.74 (m, 3H),
			2.13-2.05 (m, 3H), 1.89 (s, 3H).
298	17.2	6- (difluoromethyl)nicotinic acid
			Compound 298: (4-
			chlorophenyl)methyl N-[4-({1-[6-
			(difluoromethyl)pyridin-3-yl]-N-
			methylformamido}methyl)phenyl]carbamate.
			LCMS-APCI (POS.) m/z: 460.2 [M + H]+.
			1H NMR (400 MHz, 80° C., DMSO-d6) δ 9.55
			(s, 1H), 8.74 (s, 1H), 8.05 (d, J = 7.8 Hz, 1H),
			7.74 (d, J = 8.5 Hz, 1H), 7.50-7.40 (m, 6H),
			7.21 (s, 2H), 6.94 (t, J = 55.3 Hz, 1H), 5.15 (s,
			2H), 4.54 (s, 2H), 2.94-2.80 (m, 3H).
41	17.2	1H-pyrazole-4- carboxylic acid
			Compound 41: (4-chlorophenyl)methyl N-
			{4-[(N-methyl-1-1H-pyrazol-4-
			ylformamido)methyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 399.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 13.10 (bs, 1H),
			9.78 (s, 1H), 7.95 (bs, 2H), 7.51-7.36 (m,
			6H), 7.17 (s, 2H), 5.13 (s, 2H), 4.59 (s, 2H),
			3.12-2.81 (m, 3H).
49	17.2	1H-pyrazole-3- carboxylic acid
			Compound 49: (4-chlorophenyl)methyl N-
			{4-[(N-methyl-1-1H-pyrazol-3-
			ylformamido)methyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 399.1 [M + H]+. 1H
			NMR (400 MHz, 80° C., DMSO-d6) δ 12.95 (s,
			1H), 9.50 (s, 1H), 7.73 (s, 1H), 7.48-7.38 (m,
			6H), 7.19 (d, J = 7.8 Hz, 2H), 6.58 (s, 1H),
			5.15 (s, 2H), 4.67 (bs, 2H), 3.05 (s, 3H).
69	17.2	5-fluoro-1H-pyrazole-4- carboxylic acid
			Compound 69: (4-chlorophenyl)methyl N-
			(4-{[1-(3-fluoro-2H-pyrazol-4-yl)-N-
			methylformamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 417.3 [M + H]+.
			1H NMR (400 MHz, 80° C., DMSO-d6) δ 12.62
			(bs, 1H), 9.53 (s, 1H), 7.90 (s, 1H), 7.48-7.41
			(m, 6H), 7.16 (d, J = 8.2 Hz, 2H), 5.15 (s, 2H),
			4.55 (s, 2H), 2.92 (s, 3H).
101	16.2	1-ethyl-1H-pyrazole-5- carboxylic acid
			Compound 101: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(2-ethylpyrazol-3-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 427.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			8.71 (d, J = 8.1 Hz, 1H), 7.50-7.42 (m, 5H),
			7.40 (d, J = 8.1 Hz, 2H), 7.27 (d, J = 8.3 Hz,
			2H), 6.92 (s, 1H), 5.13 (s, 2H), 5.07 (p, J =
			7.9 Hz, 1H), 4.44 (q, J = 7.9 Hz, 2H), 1.47-1.43
			(d, J = 5.3 Hz, 3H), 1.25 (t, J = 6.3 Hz, 3H).
104	17.2	6-methylnicotinic acid
			Compound 104: (4-chlorophenyl)methyl N-
			(4-{[N-methyl-1-(6-methylpyridin-3-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 424.1 [M + H]+. 1H
			NMR (400 MHz, 80° C., DMSO-d6) δ 9.53 (s,
			1H), 8.50 (s, 1H), 7.72 (d, J = 8.1 Hz, 1H),
			7.49-7.41 (m, 6H), 7.29 (d, J = 8.2 Hz, 1H),
			7.22-7.15 (m, 2H), 5.15 (s, 2H), 4.53 (s, 2H),
			2.88 (s, 3H), 2.49 (s, 3H).
105	16.2	isonicotinic acid
			Compound 105: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-(pyridin-4-
			ylformamido)ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 410.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			9.02 (d, J = 8.0 Hz, 1H), 8.71 (s, 2H), 7.77 (s,
			2H), 7.49-7.43 (m, 4H), 7.40 (d, J = 8.1 Hz,
			2H), 7.30 (d, J = 8.3 Hz, 2H), 5.17-5.06 (m,
			3H), 1.46 (d, J = 7.0 Hz, 3H).
118	16.2	nicotinic acid
			Compound 118: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-(pyridin-3-
			ylformamido)ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 410.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
			9.02 (s, 1H), 8.94 (d, J = 8.1 Hz, 1H), 8.70
			(d, J = 4.6 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H),
			7.54-7.48 (m, 1H), 7.47-7.43 (m, 4H), 7.40
			(d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.3 Hz, 2H),
			5.17-5.07 (m, 3H), 1.46 (d, J = 7.0 Hz, 3H).
130	17.2	oxazole-5-carboxylic acid
			Compound 130: (4-chlorophenyl)methyl N-
			(4-[(N-methyl-1-1,3-oxazol-5-
			ylformamido)methyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 400.1 [M + H]+. 1H
			NMR (400 MHz, 80° C., DMSO-d6) δ 9.53 (s,
			1H), 8.45 (s, 1H), 7.65 (s, 1H), 7.48-7.40 (m,
			6H), 7.19 (d, J = 8.2 Hz, 2H), 5.15 (s, 2H),
			4.64 (s, 2H), 3.05 (s, 3H).
139	16.2	1,3-dimethyl-1H- pyrazole-5-carboxylic acid
			Compound 139: (4-chlorophenyl)methyl N-
			{4-[(1S)-1-[(2,5-dimethylpyrazol-3-
			yl)formamido]ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 427.4 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
			8.62 (d, J = 8.2 Hz, 1H), 7.49-7.43 (m, 4H),
			7.39 (d, J = 8.2 Hz, 2H), 7.26 (d, J = 8.4 Hz,
			2H), 6.71 (s, 1H), 5.13 (s, 2H), 5.09-4.99 (m,
			1H), 3.91 (s, 3H), 2.15 (s, 3H), 1.41 (d, J =
			7.0 Hz, 3H).
155	17.2	4-methyloxazole-2- carboxylic acid
			Compound 155: (4-chlorophenyl)methyl N-
			(4-{[N-methyl-1-(4-methyl-1,3-oxazol-2-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 414.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.82 (s, 1H),
			8.00 (s, 1H), 7.49-7.41 (m, 6H), 7.20 (dd, J =
			13.3, 8.3 Hz, 2H), 5.13 (s, 2H), 4.77 (d, J =
			143.0 Hz, 2H), 3.04 (d, J = 141.6 Hz, 3H),
			2.15 (d, J = 8.6 Hz, 3H).
160	17.2	3-methylisoxazole-5- carboxylic acid
			Compound 160: (4-chlorophenyl)methyl N-
			(4-{[N-methyl-1-(3-methyl-1,2-oxazol-5-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 414.1 [M+H]+. 1H
			NMR (400 MHz, 80 ° C., DMSO-d6) 8 9.56 (s,
			1H), 7.50-7.41 (m, 6H), 7.19 (bs, 2H), 6.75
			(bs, 1H), 5.15 (s, 2H), 4.59 (s, 2H), 2.98 (bs,
			3H), 2.29 (s, 3H).
182	17.2	2,4-dimethyloxazole-5- carboxylic acid
			Compound 182: (4-chlorophenyl)methyl N-
			(4-{[1-(2,4-dimethyl-1,3-oxazol-5-yl)-N-
			methylformamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 428.2 [M + H]+.
			1H NMR (400 MHz, 80° C., DMSO-d6) δ 9.53
			(s, 1H), 7.47-7.40 (m, 6H), 7.18 (d, J = 7.7 Hz,
			2H), 5.15 (s, 2H), 4.58 (s, 2H), 2.96 (s,
			3H), 2.38 (s, 3H), 2.24 (s, 3H).
190	17.2	3,4-dimethylisoxazole- 5-carboxylic acid
			Compound 190: (4-chlorophenyl)methyl N-
			(4-{[1-(3,4-dimethyl-1,2-oxazol-5-yl)-N-
			methylformamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 428.2 [M + H]+.
			1H NMR (400 MHz, 80° C., DMSO-d6) δ 9.55
			(s, 1H), 7.48-7.41 (m, 6H), 7.16 (d, J = 6.4 Hz,
			2H), 5.15 (s, 2H), 4.52 (s, 2H), 2.85 (s,
			3H), 2.35 (s, 3H), 2.17 (s, 3H).
197	17.2	3-methyl-1H-pyrazole- 4-carboxylic acid
			Compound 197: (4-chlorophenyl)methyl N-
			(4-{[N-methyl-1-(3-methyl-1H-pyrazol-4-
			yl)formamido]methyl}phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 413.3 [M + H]+. 1H
			NMR (400 MHz, 80° C., DMSO-d6) δ 12.59
			(bs, 1H), 9.51 (s, 1H), 7.58 (s, 1H), 7.47-
			7.41 (m, 6H), 7.16 (d, J = 8.3 Hz, 2H), 5.15
			(s, 2H), 4.56 (s, 2H), 2.92 (s, 3H), 2.29 (s,
			3H).
266	16.2	cyclopropanecarboxylic acid
			Compound 266: 1,3-oxazol-5-ylmethyl N-
			{4-[(1S)-1-
			(cyclopropylformamido)ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 330.2
			[M + H]+. 1H NMR (400 MHz, DMSO-d6) δ
			9.76 (s, 1H), 8.46-8.37 (m, 2H), 7.38 (d, J =
			8.1 Hz, 2H), 7.31 (s, 1H), 7.22 (d, J = 8.1 Hz,
			2H), 5.22 (s, 2H), 4.87 (p, J = 7.2 Hz, 1H),
			1.59 (p, J = 6.3 Hz, 1H), 1.32 (d, J = 6.9 Hz,
			3H), 0.70-0.57 (m, 4H).
75	16.2	3,3- difluorocyclobutane-1- carboxylic acid
			Compound 75: 1,3-oxazol-5-ylmethyl N-
			{4-[(1S)-1-[(3,3-
			difluorocyclobutyl)formamido]ethyl]phenyl}
			carbamate. LCMS-APCI (POS.) m/z: 380.2
			[M + H]+. 1H NMR (400 MHz, DMSO-d6) δ
			9.76 (s, 1H), 8.42 (s, 1H), 8.38 (d, J = 7.8 Hz,
			1H), 7.37 (d, J = 8.1 Hz, 2H), 7.30 (s, 1H),
			7.20 (d, J = 8.0 Hz, 2H), 5.21 (s, 2H), 4.86
			(p, J = 6.9 Hz, 1H), 2.90 (p, J = 8.9 Hz, 1H),
			2.74-2.57 (m, 4H), 1.31 (d, J = 6.9 Hz, 3H).
39	16.2	4-fluorobenzoic acid
			Compound 39: 1,3-oxazol-5-ylmethyl N-{4-
			[(1S)-1-[(4-
			fluorophenyl)formamido]ethyl]phenyl}
			carbamate. LCMS-APCI (POS.) m/z: 384.2
			[M + H]+. 1H NMR (400 MHz, DMSO-d6) δ
			9.76 (s, 1H), 8.75 (d, J = 8.2 Hz, 1H), 8.41 (s,
			1H), 7.99-7.86 (m, 2H), 7.38 (d, J = 8.2 Hz,
			2H), 7.33-7.22 (m, 5H), 5.20 (s, 2H), 5.09
			(p, J = 7.4 Hz, 1H), 1.44 (d, J = 7.0 Hz, 3H).
97	16.2	3,3- difluorocyclopentane-1- carboxylic acid
			Compound 97: 1,3-oxazol-5-ylmethyl N-{4-
			[(1S)-1-[(3,3-
			difluorocyclopentyl)formamido]ethyl]phenyl}
			carbamate. LCMS-APCI (POS.) m/z:
			394.2 [M + H]+. 1H NMR (400 MHz, DMSO-
			d6) δ 9.76 (s, 1H), 8.42 (s, 1H), 8.33-8.26 (m,
			1H), 7.37 (d, J = 8.2 Hz, 2H), 7.30 (s, 1H),
			7.20 (d, J = 8.1 Hz, 2H), 5.21 (s, 2H), 4.83
			(p, J = 7.5 Hz, 1H), 2.90 (p, J = 9.0 Hz, 1H),
			2.31-1.91 (m, 5H), 1.88-1.66 (m, 1H), 1.31
			(d, J = 6.9 Hz, 3H).
22	16.2	6,6- difluorospiro[3.3]heptane- 2-carboxylic acid
			Compound 22: 1,3-oxazol-5-ylmethyl N-{4-
			[(1S)-1-({6,6-difluorospiro[3.3]heptan-2-
			yl}formamido)ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 420.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			8.41 (s, 1H), 8.07 (d, J = 8.0 Hz, 1H), 7.36
			(d, J = 8.1 Hz, 2H), 7.30 (s, 1H), 7.18 (d, J =
			8.1 Hz, 2H), 5.20 (s, 2H), 4.83 (p, J = 7.0,
			6.5 Hz, 1H), 2.95 (p, J = 8.6 Hz, 1H), 2.62 (t, J =
			12.7 Hz, 2H), 2.49-2.42 (m, 2H), 2.30-2.21
			(m, 1H), 2.20-2.10 (m, 3H), 1.28 (d, J = 6.9 Hz,
			3H).
230	16.2	(1R,3r,5S)-6,6- difluorobicyclo[3.1.0] hexane-3-carboxylic acid
			Compound 230: 1,3-oxazol-5-ylmethyl N-
			{4-[(1S)-1-{[(1R,3r,5S)-6,6-
			difluorobicyclo[3.1.0]hexan-3-
			yl]formamido}ethyl]phenyl}carbamate.
			LCMS-ESI (POS.) m/z: 406.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H),
			8.42 (s, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.36
			(d, J = 8.1 Hz, 2H), 7.30 (s, 1H), 7.17 (d, J =
			8.1 Hz, 2H), 5.20 (s, 2H), 4.82 (p, J = 7.4 Hz,
			1H), 3.13 (p, J = 9.6 Hz, 1H), 2.18 (d, J =
			12.3 Hz, 4H), 1.86 (t, J = 10.5 Hz, 1H), 1.78z
			(t, J = 10.6 Hz, 1H), 1.29 (d, J = 6.9 Hz, 3H).
68	16.2	(1R,3s,5S)-6,6- difluorobicyclo[3.1.0] hexane-3-carboxylic acid
			Compound 68: 1,3-oxazol-5-ylmethyl N-{4-
			[(1S)-1-{[(1R,3s,5S)-6,6-
			difluorobicyclo[3.1.0]hexan-3-
			yl]formamido}ethyl]phenyl}carbamate.
			LCMS-ESI (POS.) m/z: 406.1 [M+H]+. 1H
			NMR (400 MHz, DMSO-d6) 8 9.75 (s, 1H),
			8.41 (s, 1H), 8.30 (d, J = 7.8 Hz, 1H), 7.36
			(d, J = 7.6 Hz, 2H), 7.30 (s, 1H), 7.18 (d, J =
			8.5 Hz, 2H), 5.20 (s, 2H), 4.82 (p, J = 7.2 Hz,
			1H), 2.70-2.57 (m, 1H), 2.18-1.96 (m, 6H),
			1.28 (d, J = 6.9 Hz, 3H).

Urea Synthesis

Example N

Preparation of (4-chlorophenyl)methyl N-{4-[1(morpholine-4-carbonylamino)methyl]phenyl}carbamate (Compound 270)

To a solution of (4-chlorophenyl)methyl N-[4-(aminomethyl)phenyl]carbamate hydrochloride (100 mg, 0.31 mmol) and N,N-diisopropylethylamine (0.21 mL, 1.22 mmol) in acetonitrile (1 mL) and DCM (1 mL) was added morpholine (0.14 mL, 1.83 mmol), carbonyldiimidazole (178.4 mg, 1.1 mmol), the mixture was stirred at 24° C. for 15 h, concentrated and purified by reverse phase prep HPLC using a gradient of 3-40% water/acetonitrile with 0.1% formic acid to yield product (4-chlorophenyl)methyl N-{4-[(morpholine-4-carbonylamino)methyl]phenyl}carbamate (61.0 mg, 0.15 mmol, 49% yield). LCMS-APCI (POS.) m/z: 404.2 [M+H]⁺. ¹H NMR (400 MHz, DMSO-d₆) δ 9.71 (s, 1H), 7.49-7.42 (m, 4H), 7.37 (d, J=8.1 Hz, 2H), 7.16 (d, J=8.0 Hz, 2H), 7.02 (t, J=6.2 Hz, 1H), 5.13 (s, 2H), 4.16 (d, J=5.6 Hz, 2H), 3.56-3.51 (m, 4H), 3.30-3.24 (m, 4H).

Compounds in the following table were prepared in a similar manner as Compound 270, using the intermediate and amine as listed.

Co
#	Intermediate	Amine	Structure, Name and Data
184	15.2	4- methoxypiperidine
			Compound 184: (4
			chlorophenyl)methyl N-{4-[(4-
			methoxypiperidine-1-
			carbonylamino)methyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 432.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.70 (s, 1H),
			7.49-7.42 (m, 4H), 7.37 (d, J = 8.1 Hz, 2H),
			7.14 (d, J = 8.0 Hz, 2H), 6.98 (t, J = 5.2 Hz,
			1H), 5.13 (s, 2H), 4.14 (d, J = 5.6 Hz, 2H),
			3.66 (d, J = 13.5 Hz, 2H), 3.31-3.36 (m,
			1H), 3.24 (s, 3H), 2.95 (dd, J = 13.2, 9.8 Hz,
			2H), 1.86-1.69 (m, 2H), 1.35-1.18 (m, 2H).
96	16.2	azetidine
			Compound 96: 4-chlorophenyl)methyl N-
			{4-[(1S)-1-(azetidine-1-
			carbonylamino)ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 388.1 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.70 (s, 1H),
			7.46 (d, J = 1.9 Hz, 4H), 7.37 (d, J = 8.2 Hz,
			2H), 7.21 (d, J = 8.2 Hz, 2H), 6.51-6.47 (m,
			1H), 5.13 (s, 2H), 4.70 (t, J = 7.5 Hz, 1H),
			3.78 (t, J = 7.8 Hz, 4H), 2.14-2.06 (m, 2H),
			1.30 (d, J = 7.3 Hz, 3H).
144	16.2	3-methylazetidine
			Compound 144: (4-
			chlorophenyl)methyl N-{4-[(1S)-1-(3-
			methylazetidine-1-
			carbonylamino)ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 402.1 [M + H]+. 1H
			NMR (400 MHz, Methanol-d4) δ 7.50-7.35
			(m, 6H), 7.33-7.22 (m, 2H), 5.17 (s, 2H),
			4.60 (s, 1H), 4.06 (t, J = 8.1 Hz, 2H), 3.50 (t,
			J = 6.6 Hz, 2H), 2.73-2.64 (m, 1H), 1.43 (d,
			J = 6.9 Hz, 3H), 1.25 (d, J = 6.8 Hz, 3H). Two
			N—H hydrogens. Two hydrogens exchange
			with solvent.
170	16.2	3- methoxyazetidine
			Compound 170: (4-chlorophenyl)methyl
			N-{4-[(1S)-1-(3-methoxyazetidine-1-
			carbonylamino)ethyl]phenyl}carbamate.
			LCMS-APCI (POS.) m/z: 418.2 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.71 (s, 1H),
			7.46 (d, J = 2.5 Hz, 4H), 7.37 (d, J = 7.5 Hz,
			2H), 7.21 (d, J = 8.6 Hz, 2H), 6.62 (d, J = 8.2
			Hz, 1H), 5.14 (s, 2H), 4.70 (t, J = 7.9 Hz, 1H),
			4.11 (s, 1H), 3.96 (s, 2H), 3.64-3.56 (m, 2H),
			3.18 (d, J = 2.6 Hz, 3H), 1.31 (d, J = 7.2 Hz,
			3H).
265	15.2	azetidine
			Compound 265: (4-
			chlorophenyl)methyl N-{4-[(azetidine-1-
			carbonylamino)methyl]phenyl}carbamate.
			LCMS-ES (Pos) m/z: 374 [M + H]+. 1H NMR
			(400 MHz, DMSO-d6) δ 9.75 (s ,1H), 7.46 (s,
			4H), 7.38 (d, J = 8.2 Hz, 2H), 7.15 (d, J = 8.1
			Hz, 2H), 6.71 (s, 1H), 5.13 (s, 2H), 4.10 (d, J =
			5.1 Hz, 2H), 3.79 (t, J = 7.3 Hz, 3H), 2.11
			(dd, J = 15.4, 7.7 Hz, 3H).
286	15.2	piperidine
			Compound 286: (4-
			chlorophenyl)methyl N-{4-[(piperidine-1-
			carbonylamino)methyl]phenyl}carbamate.
			LCMS-ES (Pos) m/z: 402 [M + H]+. 1H NMR
			(400 MHz, DMSO-d6) δ 9.72 (s, 1H), 7.52-
			7.44 (m, 4H), 7.37 (d, J = 8.1 Hz, 2H), 7.15
			(d, J = 8.2 Hz, 2H), 6.92 (t, J = 6.0 Hz, 1H),
			5.13 (s, 2H), 4.15 (d, J = 5.7 Hz, 2H), 3.31-
			3.25 (m, 4H), 1.57-1.49 (m, 2H), 1.45-1.37
			(m, 4H).
309	15.2	3,3- Difluoropiperdine
			Compound 309: (4-
			chlorophenyl)methyl N-{4-[(4,4-
			difluoropiperidine-1-
			carbonylamino)methyl]phenyl}carbamate.
			LCMS-ES (Pos) m/z: 438 (M + H). 1H NMR
			(400 MHz, DMSO-d6) δ 9.74 (s, 1H), 7.46 (s,
			2H), 7.51-7.35 (m, 4H), 7.24-7.13 (m, 3H),
			5.13 (s, 2H), 4.17 (d, J = 5.7 Hz, 2H), 3.34 (s,
			3H), 1.89 (dt, J = 14.5, 8.5 Hz, 5H).
258	15.2	tert-butyl piperazine- 1-carboxylate
			Compound 258: (4-
			chlorophenyl)methyl N-(4-{[4-(2,2-
			difluoroethyl)piperazine-1-
			carbonylamino]methyl}phenyl)carbamate.
			LCMS-ES (Pos) m/z: 467 [M + H]+. 1H NMR
			(400 MHz, DMSO-d6) δ 9.73 (s, 1H), 7.46
			(s, 4H), 7.38 (d, J = 8.1 Hz, 2H), 7.15 (d, J =
			8.1 Hz, 2H), 7.02 (t, J = 5.9 Hz, 2H), 6.17
			(m, 1H) 5.13 (s, 2H), 4.16 (d, J = 5.6 Hz,
			2H), 3.30 (t, J = 4.8 Hz, 3H), 2.73 (td, J =
			15.7, 4.4 Hz, 2H), 2.46 (d, J = 5.4 Hz, 4H).
154	16.2	morpholine
			Compound 154: 4-chlorobenzyl (S)-(4-(1-
			(morpholine-4-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 418.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.69 (s,
			1H), 7.45 (d, J = 2.3 Hz, 4H), 7.36 (d, J = 8.3
			Hz, 2H), 7.21 (d, J = 8.6 Hz, 2H), 6.71 (d, J =
			7.9 Hz, 1H), 5.13 (s, 2H), 4.77 (t, J = 7.4
			Hz, 1H), 3.52 (t, J = 4.6 Hz, 4H), 3.26 (t, J =
			4.7 Hz, 4H), 1.32 (d, J = 7.1 Hz, 3H).
145	16.2	4- methylpiperidine
			Compound 145: 4-chlorobenzyl (S)-(4-(1-
			(4-methylpiperidine-1-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 430.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.68 (s,
			1H), 7.45 (d, J = 2.2 Hz, 4H), 7.35 (d, J = 8.1
			Hz, 2H), 7.20 (d, J = 8.1 Hz, 2H), 6.59 (d, J =
			7.9 Hz, 1H), 5.13 (s, 2H), 4.79-4.73 (m, 1H),
			3.95 (d, J = 13.2 Hz, 2H), 2.59 (s, 3H), 1.54
			(d, J = 13.7 Hz, 2H), 1.31 (d, J = 7.0 Hz, 3H),
			0.93 (d, J = 11.8 Hz, 2H), 0.88 (d, J = 6.3 Hz,
			3H).
103	16.2	pyrrolidine
			Compound 103: 4-chlorobenzyl (S)-(4-(1-
			(pyrrolidine-1-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 402.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.69 (s,
			1H), 7.46 (d, J = 2.1 Hz, 4H), 7.36 (d, J = 8.3
			Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 6.23 (d, J =
			8.3 Hz, 1H), 5.13 (s, 2H), 4.78 (t, J = 7.6
			Hz, 1H), 3.23 (d, J = 6.2 Hz, 4H), 1.79 (d, J =
			6.2 Hz, 4H), 1.33 (d, J = 7.2 Hz, 3H).
72	16.2	4- methoxypiperidine
			Compound 72: 4-chlorobenzyl (S)-(4-(1-
			(4-methoxypiperidine-1-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 446.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.69 (s,
			1H), 7.45 (d, J = 2.2 Hz, 4H), 7.35 (d, J = 8.2
			Hz, 2H), 7.20 (d, J = 8.2 Hz, 2H), 6.67 (d, J =
			8.1 Hz, 1H), 5.13 (s, 2H), 4.75 (t, J = 7.3 Hz,
			1H), 3.67 (d, J = 13.8 Hz, 2H), 3.24 (s, 3H),
			2.93 (t, J = 11.4 Hz, 2H), 1.76 (d, J = 12.1 Hz,
			2H), 1.31 (d, J = 7.1 Hz, 3H), 1.25 (d, J = 10.2
			Hz, 2H), 1.09 (m, 1H).
112	17.2	azetidine
			Compound 112: 4-chlorobenzyl (4-((N-
			methylazetidine-1-
			carboxamido)methyl)phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 388.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.76 (s,
			1H), 7.45 (s, 4H), 7.41 (d, J = 7.9 Hz, 2H),
			7.14 (d, J = 8.0 Hz, 2H), 5.13 (s, 2H), 4.27 (s,
			2H), 3.88 (t, J = 7.6 Hz, 4H), 2.64 (s, 3H),
			2.17-2.07 (m, 2H).
128	17.2	pyrrolidine
			Compound 128: 4-chlorobenzyl (4-((N-
			methylpyrrolidine-1-
			carboxamido)methyl)phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 402.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.76 (s,
			1H), 7.45 (s, 4H), 7.41 (d, J = 8.3 Hz, 2H),
			7.18 (d, J = 8.2 Hz, 2H), 5.13 (s, 2H), 4.25 (s,
			2H), 3.26 (d, J = 6.5 Hz, 4H), 2.64 (s, 3H),
			1.75 (d, J = 6.0 Hz, 4H).
42	17.2	4-methoxy- piperidine
			Compound 42: 4-chlorobenzyl (4-((4-
			methoxy-N-methylpiperidine-1-
			carboxamido)methyl)phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 446.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.77 (s,
			1H), 7.45 (s, 4H), 7.42 (d, J = 8.2 Hz, 2H),
			7.15 (d, J = 8.1 Hz, 2H), 5.13 (s, 2H), 4.22 (s,
			2H), 3.45-3.3 (m, 3H), 3.24 (s, 3H), 2.87 (s,
			2H), 2.63 (s, 3H), 1.87-1.77 (m, 2H), 1.38
			(d, J = 10.6 Hz, 2H).
89	18.2	azetidine
			Compound 89: 4-chlorobenzyl (S)-(4-(1-
			(N-methylazetidine-1-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 402.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.78 (s,
			1H), 7.46 (s, 4H), 7.42 (d, J = 8.5 Hz, 2H),
			7.19 (d, J = 8.2 Hz, 2H), 5.23 (d, J = 7.0 Hz,
			1H), 5.14 (s, 2H), 3.89 (t, J = 7.7 Hz, 4H),
			2.41 (s, 3H), 2.18-2.09 (m, 2H), 1.39 (d, J =
			7.1 Hz, 3H).
143	18.2	pyrrolidine
			Compound 143: 4-chlorobenzyl (S)-(4-(1-
			(N-methylpyrrolidine-1-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 416.5 [M + H]+. 1H
			NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H),
			7.46 (s, 4H), 7.41 (d, J = 8.3 Hz, 2H), 7.22 (d,
			J = 8.1 Hz, 2H), 5.13 (s, 2H), 5.08 (d, J = 7.3
			Hz, 1H), 3.26 (d, J = 6.3 Hz, 4H), 2.42 (s, 3H),
			1.75 (s, 4H), 1.42 (d, J = 7.4 Hz, 3H).
134	18.2	4-methoxy- piperidine
			Compound 134: 4-chlorobenzyl (S)-(4-(1-
			(4-methoxy-N-methylpiperidine-1-
			carboxamido)ethyl)phenyl)carbamate.
			LCMS-APCI (POS.) m/z: 460.1 [M + H]+.
			1H NMR (400 MHz, DMSO-d6) δ 9.77 (s,
			1H), 7.45 (s, 4H), 7.41 (d, J = 7.5 Hz, 2H),
			7.19 (d, J = 8.2 Hz, 2H), 5.13 (s, 2H), 5.00 (s,
			1H), 3.24 (s, 3H), 2.85 (s, 3H), 2.44 (s, 3H),
			1.82 (d, 3H), 1.42 (d, J = 7.1 Hz, 4H), 1.37
			(m, 2H), 1.23 (s, 1H).

Ester Hydrolysis and Amide Synthesis

Example O

Preparation of (4-chlorophenyl)methyl N-{4-[2-(4-hydroxy-4-methylpiperidin-1-yl)-2-oxoethyl]phenyl}carbamate (Compound 116)

Step 1: Preparation of [4-({[(4-chlorophenyl)methoxy]carbonyl}amino)phenyl]acetic acid

A mixture of ethyl 2-[4-({[(4-chlorophenyl)methoxy]carbonyl}amino)phenyl]acetate, 150 mL EtOH, and 150 mL 1N NaOH was stirred at rt for 18 h. The mixture was concentrated, acidified to pH=2 with 2N HCl, filtered and dried in vacuum to afford an off-white solid (5.96 g, 67%). LCMS-ES (Pos) m/z: 320 [M+H]⁺.

Step 2: Preparation (4-chlorophenyl)methyl N-{4-[2-(4-hydroxy-4-methylpiperidin-1-yl)-2-oxoethyl]phenyl}carbamate

A mixture of [4-({[(4-chlorophenyl)methoxy]carbonyl}amino)phenyl]acetic acid (150 mg, 0.47 mmol, 1 equiv), 4-methylpiperidin-4-ol (54 mg, 0.47 mmol, 1 equiv), HATU (214 mg, 0.563 mmol, 1.2 equiv), DIEA (0.123 mL, 0.704 mmol, 1.5 equiv) and DMF (1 mL) was stirred at rt for 1 h. The mixture was purified by prep HPLC affording a light brown solid. LCMS-ES (Pos) m/z: 417 [M+H]⁺. ¹H NMR (400 MHz, DMSO-d₆) δ 9.73 (s, 1H), 7.46 (d, J=1.8 Hz, 4H), 7.38 (d, J=8.1 Hz, 2H), 7.12 (d, J=8.0 Hz, 2H), 5.14 (s, 2H), 4.34 (s, 1H), 3.91 (d, J=13.1 Hz, 1H), 3.57 (d, J=13.3 Hz, 1H), 3.33 (s, 2H), 3.33-3.25 (m, 1H), 3.04 (t, J=11.9 Hz, 1H), 1.41 (d, J=15.1 Hz, 1H), 1.38-1.17 (m, 2H), 1.09 (s, 2H).

Compounds in the following table were prepared in a similar manner as Compound 116, using the intermediate 21.2 and amine as listed.

Co #	Amine	Structure, Name and Data
64	(1R,4R)-4- methoxycyclohexan-1- aminium chloride
		Compound 64: (4-chlorophenyl)methyl N-[4-
		({[(1R,4R)-4-
		methoxycyclohexyl]carbamoyl}methyl)phenyl]carbamate.
		LCMS-ES (Pos) m/z: 431 [M + H]+. 1H NMR (400
		MHz, DMSO-d6) δ 9.71 (s, 1H), 7.53-7.22 (m, 6H), 7.14
		(d, J = 8.1 Hz, 2H), 5.14 (d, J = 2.6 Hz, 2H), 3.33-3.50
		(m, 6H), 3.09 (s, 1H), 1.96 (s, 2H), 1.76 (s, 2H), 1.16 (q, J =
		9.9, 9.5 Hz, 4H).
156	tert-butyl piperazine- 1-carboxylate
		Compound 156: methyl 4-(2-(4-((((4-
		chlorobenzyl)oxy)carbonyl)amino)phenyl)acetyl)piperazine-
		1-carboxylate. LCMS-ES (Pos) m/z: 446 [M + H]+.
		1H NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H), 7.46 (d, J =
		1.7 Hz, 4H), 7.42-7.30 (m, 2H), 7.13 (d, J = 8.3 Hz,
		2H), 5.14 (s, 2H), 3.68-3.58 (m, 5H), 3.46 (t, J = 5.8
		Hz, 3H), 3.27 (d, J = 5.0 Hz, 2H), 1.26 (q, J = 7.3, 6.6
		Hz, 3H).
111	piperdine
		Compound 111: (4-chlorophenyl)methyl N-{4-[2-oxo-
		2-(piperidin-1-yl)ethyl]phenyl}carbamate Example: .
		LCMS-ES (Pos) m/z: 387 (M + H). 1H NMR (400 MHz,
		DMSO-d6) δ 9.75 (s, 1H) 7.46 (s, 4H), 7.39 (d, J = 8.2 Hz,
		2H), 7.13 (d, J = 8.2 Hz, 2H), 5.14 (s, 2H), 3.65 (s, 2H),
		3.41 (dt, J = 10.1, 5.4 Hz, 4H), 1.53 (p, J = 6.0 Hz, 2H),
		1.35 (m, 4H).
119	4-hydroxy piperidine
		Compound 119: (4-chlorophenyl)methyl N-{4-[2-(4-
		hydroxypiperidin-1-yl)-2-oxoethyl]phenyl}carbamate.
		LCMS-ES (Pos) m/z: 403 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 9.74 (s, 1H), 7.42 (d, J = 33.5 Hz, 5H), 7.13
		(d, J = 8.2 Hz, 2H), 5.14 (s, 2H), 4.12-3.78 (m, 2H), 3.62
		(m, 5H), 3.13 (td, J = 10.5, 10.0, 5.0 Hz, 1H), 2.97 (m,
		1H), 1.61 (dd, J = 27.8, 12.1 Hz, 2H), 1.25 (m, 2H).
161	(s)-3- methoxypiperidine
		Compound 161: 4-chlorobenzyl (S)-(4-(2-(3-
		methoxypiperidin-1-yl)-2-oxoethyl)phenyl)carbamate.
		LCMS-ES (Pos) m/z: 417 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 9.74 (s, 1H), 7.47 (s, 4H), 7.39 (d, J = 8.0 Hz,
		2H), 7.13 (d, J = 8.0 Hz, 2H), 5.14 (s, 2H), 3.79-3.67 (m,
		3H), 3.63 (m, 2H), 3.34 (s, 3H), 3.27-3.09 (m, 2H), 1.81
		(s, 1H), 1.56 (s, 1H), 1.45 (s, 1H), 1.22 (d, J = 18.0 Hz,
171	(s)-3- hydroxypiperidine
		Compound 171: 4-chlorobenzyl (S)-(4-(2-(3-
		hydroxypiperidin-1-yl)-2-oxoethyl)phenyl)carbamate.
		LCMS-ES (Pos) m/z: 403 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 9.74 (s, 1H), 7.46 (d, J = 2.1 Hz, 4H), 7.38
		(d, J = 8.1 Hz, 2H), 7.16-7.08 (m, 2H), 5.14 (s, 2H),
		3.64 (q, J = 13.1, 11.2 Hz, 4H), 3.01 (d, J = 15.8 Hz,
		2H), 1.78 (s, 1H), 1.58 (d, J = 18.2 Hz, 1H), 1.38 (d, J =
		10.6 Hz, 1H), 1.22 (dt, J = 43.8, 11.7 Hz, 3H).
339	3-amino oxetane
		Compound 339: 4-chlorobenzyl (4-(2-(oxetan-3-
		ylamino)-2-oxoethyl)phenyl)carbamate. LCMS-ES
		(Pos) m/z: 375 [M + H]+. 1H NMR (400 MHz, DMSO-d6)
		δ 9.73 (s, 1H), 8.77 (d, J = 6.4 Hz, 1H), 7.46 (s, 4H), 7.38
		(d, J = 8.1 Hz, 2H), 7.16 (d, J = 8.1 Hz, 2H), 5.14 (s,
		2H), 4.72 (dt, J = 21.7, 7.0 Hz, 3H), 4.40 (t, J = 6.0 Hz,
		2H), 3.33 (s, 1H).
183	2,2-dimethylazetidine
		Compound 183: (4-chlorophenyl)methyl N-{4-[2-(2,2-
		dimethylazetidin-1-yl)-2-oxoethyl]phenyl}carbamate.
		LCMS-ES (Pos) m/z: 387 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 9.73 (s, 1H), 7.46 (d, J = 2.1 Hz, 4H), 7.38
		(d, J = 8.1 Hz, 2H), 7.12 (d, J = 8.6 Hz, 2H), 5.76 (d, J =
		1.8 Hz, 2H), 5.14 (s, 2H), 3.98 (m, 1H), 3.23 (s, 1H), 1.99
		(dt, J = 23.9, 7.8 Hz, 2H), 1.51 (d, J = 2.2 Hz, 1H), 1.41
		(s, 5H).
194	tert-butyl piperazine- 1-carboxylate
		Compound 194: (4-chlorophenyl)methyl N-(4-{2-[4-
		(oxetan-3-yl)piperazin-1-yl]-2-
		oxoethyl}phenyl)carbamate. LCMS-ES (Pos) m/z: 444
		[M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
		7.46 (s, 4H), 7.38 (d, J = 8.1 Hz, 2H), 7.12 (d, J = 8.1 Hz,
		2H), 5.14 (s, 2H), 4.51 (s, 2H), 4.41 (s, 2H), 3.64 (s, 2H),
		3.48 (s, 3H), 2.16 (m, 5H).
199	3-amino-6-picoline
		Compound 199: (4-chlorophenyl)methyl N-(4-{[(6-
		methylpyridin-3-
		yl)carbamoyl]methyl}phenyl)carbamate.
		LCMS-ES (Pos) m/z: 410 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 10.71 (s, 1H), 9.77 (s, 1H), 8.93 (s, 1H), 8.19
		(dd, J = 8.7, 2.4 Hz, 1H), 7.65 (d, J = 8.7 Hz, 1H), 7.46 (s,
		4H), 7.42 (d, J = 8.2 Hz, 2H), 7.24 (d, J = 8.2 Hz, 2H),
		5.76 (d, J = 1.7 Hz, 2H), 5.14 (s, 2H), 2.58 (d, J = 1.9 Hz,
		3H).
202	(S)-(+)-prolinol
		Example 202: (4-chlorophenyl)methyl N-(4-{2-[(2S)-2-
		(hydroxymethyl)pyrrolidin-1-yl]-2-
		oxoethyl}phenyl)carbamate. LCMS-ES (Pos) m/z: 403
		(M + H). 1H NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
		7.46 (s, 4H), 7.38 (d, J = 8.2 Hz, 2H), 7.20-7.05 (m,
		2H), 5.14 (s, 2H), 3.93 (s, 1H), 3.54-3.18 (m, 8H), 1.83
		(dq, J = 31.0, 7.9 Hz, 4H).
212	4-fluoropiperidine
		Compound 212: (4-chlorophenyl)methyl N-{4-[2-(4-
		fluoropiperidin-1-yl)-2-oxoethyl]phenyl}carbamate.
		LCMS-ES (Pos) m/z: 405 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 9.75 (s, 1H), 7.46 (s, 4H), 7.39 (d, J = 8.1
		Hz, 2H), 7.14 (d, J = 8.2 Hz, 2H), 5.14 (s, 2H), 4.82 (d, J =
		48 Hz, 1H), 3.65 (s, 1H), 3.56 (s, 1H), 3.32 (s, 4H),
		1.73 (s, 2H), 1.59 (s, 2H), 1.53 (s, 1H).
215	2-methylpyrolidine
		Compound 215: (4-chlorophenyl)methyl N-{4-[2-(2-
		methylpyrrolidin-1-yl)-2-oxoethyl]phenyl}carbamate.
		LCMS-ES (Pos) m/z: 387 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 9.73 (s, 2H), 7.46 (d, J = 2.2 Hz, 2H), 7.38
		(d, J = 8.1 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 5.14 (s, 2H),
		4.01 (s, 1H), 3.51 (s, 1H), 3.43 (dd, J = 18.0, 8.9 Hz, 2H),
		1.93-1.88 (m, 2H), 1.81 (s, 2H), 1.49 (s, 1H), 1.16-1.04
		(m, 4H).
220	morpholine
		Compound 220: (4-chlorophenyl)methyl N-{4-[2-
		(morpholin-4-yl)-2-oxoethyl]phenyl}carbamate
		LCMS-ES (Pos) m/z: 389 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 9.74 (s, 1H), 7.46 (s, 4H), 7.39 (d, J = 8.2 Hz,
		2H), 7.13 (d, J = 8.2 Hz, 2H), 5.14 (s, 2H), 3.64 (s, 2H),
		3.52 (d, J = 4.7 Hz, 8H).
221	(1R,4R)-4- (difluoromethoxy) cyclohexan-1-amine
		Compound 221: (4-chlorophenyl)methyl N-[4-
		({[(1r,4r)-4-
		(difluoromethoxy)cyclohexyl]carbamoyl}methyl)phenyl]
		carbamate. LCMS-ES (Pos) m/z:467 (M + H). 1H NMR
		(400 MHz, DMSO-d6) δ 9.74 (s, 2H), 7.72-6.97 (m, 7H),
		5.14 (s, 2H), 4.20 (t, J = 15.2 Hz, 1H), 3.78 (d, J = 13.6
		Hz, 1H), 3.62 (s, 2H), 2.63 (d, J = 11.9 Hz, 1H), 2.27 (t, J =
		11.8 Hz, 1H), 1.82-0.94 (m, 5H), 0.80 (dd, J = 19.9,
		6.6 Hz, 3H).
229	(R)-3- methoxypiperidine
		Compound 229: (4-chlorophenyl)methyl N-(4-{2-
		[(3R)-3-methoxypiperidin-1-yl]-2-
		oxoethyl}phenyl)carbamate. LCMS-ES (Pos) m/z: 417
		[M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
		7.46 (s, 4H), 7.39 (d, J = 8.1 Hz, 2H), 7.17-7.09 (m, 2H),
		5.14 (s, 2H), 3.71-3.50 (m, 2H), 3.39 (m, 3H), 3.24 (s,
		3H), 3.16 (d, J = 13.0 Hz, 2H), 1.81 (s, 1H), 1.56 (s, 1H),
		1.45 (s, 1H), 1.22 (d, J = 16.3 Hz, 1H).
235	2-oxopiperazine
		Compound 235: (4-chlorophenyl)methyl N-{4-[2-oxo-
		2-(3-oxopiperazin-1-yl)ethyl]phenyl}carbamate.
		LCMS-ES (Pos) m/z: 402 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 9.75 (s, 1H), 7.46 (s, 4H), 7.39 (d, J = 8.1
		Hz, 2H), 7.13 (t, J = 9.3 Hz, 2H), 5.14 (s, 2H), 4.04 (s,
		1H), 3.94 (s, 1H), 3.68-3.56 (m, 3H), 3.32 (s, 2H), 3.13
		(d, J = 14.6 Hz, 2H).
237	(3R)-3-piperidinol
		Compound 237: (4-chlorophenyl)methyl N-(4-{2-
		[(3R)-3-hydroxypiperidin-1-yl]-2-
		oxoethyl}phenyl)carbamate
		LCMS-ES (Pos) m/z: 403 (M + H) 1H NMR (400 MHz,
		DMSO-d6) δ 9.74 (s, 1H), 7.46 (d, J = 2.3 Hz, 4H), 7.38
		(d, J = 8.1 Hz, 2H), 7.11 (dd, J = 8.3, 3.8 Hz, 2H), 5.14 (s,
		2H), 4.83 (s, 1H), 4.13 (d, J = 12.0 Hz, 1H), 3.64 (q, J =
		13.3, 11.2 Hz, 3H), 2.99 (s, 1H), 2.55 (m, 1H), 1.78 (s,
		1H), 1.58 (d, J = 18.0 Hz, 1H), 1.38 (d, J = 10.6 Hz, 1H),
		1.27 (t, J = 11.4 Hz, 1H), 1.15 (d, J = 12.4 Hz, 1H).
240	4-methyl piperidine
		Compound 240: (4-chlorophenyl)methyl N-{4-[2-(4-
		methylpiperidin-1-yl)-2-oxoethyl]phenyl}carbamate.
		LCMS-ES (Pos) m/z: 401 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 9.73 (s, 1H), 7.55-6.97 (m, 86H), 5.14 (s,
		2H), 4.34 (d, J = 13.0 Hz, 1H), 3.88 (d, J = 13.5 Hz, 1H),
		3.34 (s, 3H), 2.92 (t, J = 13.1 Hz, 1H), 1.69-1.46 (m, 3H),
		0.86 (m,5H).
244	(3S)-3- methylpyrrolidine
		Compound 244: (4-chlorophenyl)methyl N-(4-{2-
		[(3S)-3-methylpyrrolidin-1-yl]-2-
		oxoethyl}phenyl)carbamate
		LCMS-ES (Pos) m/z: 387 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 9.73 (s, 1H), 7.46 (d, J = 2.2 Hz, 4H), 7.38
		(d, J = 8.1 Hz, 2H), 7.13 (d, J = 8.1 Hz, 2H), 5.14 (s, 2H),
		3.69-3.54 (m, 1H), 3.51-3.37 (m, 1H), 3.35 (s, 2H),
		3.20 (q, J = 9.8, 9.3 Hz, 1H), 2.96 (t, J = 9.2 Hz, 1H), 2.25-
		2.13 (m, 1H), 1.99-1.91 (m, 1H), 1.57-1.39 (m, 1H),,
		0.99 (m, 3H).
256	(3R)-3- methylpiperidine
		Compound 256: (4-chlorophenyl)methyl N-(4-{2-
		[(3R)-3-methylpiperidin-1-yl]-2-
		oxoethyl}phenyl)carbamate. LCMS-ES (Pos) m/z: 401
		(M + H). 1H NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
		7.46 (s, 4H), 7.38 (d, J = 8.2 Hz, 2H), 7.13 (d, J = 8.1 Hz,
		2H), 5.14 (s, 2H), 4.20 (t, J = 15.2 Hz, 1H), 3.78 (d, J =
		13.6 Hz, 1H), 3.62 (s, 2H), 2.61 (t, J = 12.4 Hz, 1H), 2.27
		(t, J = 11.8 Hz, 1H), 1.68 (d, J = 12.3 Hz, 1H), 1.54 (dd, J =
		27.6, 12.6 Hz, 1H), 1.24 (s, 1H), 1.06 (d, J = 12.4 Hz,
		1H), 0.80 (m, 4H).
257	(2S)-2- piperidinemethanol
		Compound 257: (4-chlorophenyl)methyl N-(4-{2-
		[(2S)-2-(hydroxymethyl)piperidin-1-yl]-2-
		oxoethyl}phenyl)carbamate. LCMS-ES (Pos) m/z: 417
		[M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
		7.46 (d, J = 2.3 Hz, 4H), 7.39 (d, J = 8.2 Hz, 2H), 7.12 (s,
		2H), 5.14 (s, 1H), 4.83 (s, 1H), 4.64 (m, 1H), 4.53 (m,
		1H), 4.35 (d, J = 13.8 Hz, 1H), 3.97 (s, 1H), 3.75 (t, J =
		17.3 Hz, 2H), 3.46 (s, 1H), 3.32 (d, J = 2.2 Hz, 3H), 1.59
		(s, 1H), 1.46 (s, 1H), 1.22 (s, 2H).
261	(S)-3-methylpiperidine
		Compound 261. (4-chlorophenyl)methyl N-(4-{2-[(3S)-
		3-methylpiperidin-1-yl]-2-oxoethyl}phenyl)carbamate
		LCMS-ES (Pos) m/z: 401 (M + H). 1H NMR (400 MHz,
		DMSO-d6) δ 9.74 (s, 1H), 7.47 (s, 1H), 7.46 (s, 3H), 7.39
		(d, J = 8.0 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 5.14 (s, 2H),
		3.79-3.67 (m, 1H), 3.63 (s, 1H), 3.34 (s, 2H), 3.27-3.09
		(m, 3H), 1.81 (s, 1H), 1.56 (s, 1H), 1.45 (s, 1H), 1.22 (d, J =
		18.0 Hz, 1H), 0.8 (m, 3H).
274	4,4-difluoropiperidine
		Compound 274: (4-chlorophenyl)methyl N-{4-[2-(4,4-
		difluoropiperidin-1-yl)-2-oxoethyl]phenyl}carbamate.
		LCMS-ES (Pos) m/z: 423 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 9.75 (s, 1H), 7.46 (s, 4H), 7.40 (d, J = 8.0
		Hz,2H), 7.14 (d, J = 8.1 Hz, 2H), 5.14 (s, 2H), 3.70 (s, 2H),
		3.56 (d, J = 6.1 Hz, 4H), 1.91-1.81 (m, 4H).
280	(1S,4S)-4- methoxycyclo- hexanamine
		Compound 280: (4-chlorophenyl)methyl N-[4-
		({[(1s,4s)-4-
		methoxycyclohexyl]carbamoyl}methyl)phenyl]carbamate.
		LCMS-ES (Pos) m/z: 431 [M + H]+. 1H NMR (400
		MHz, DMSO-d6) δ 9.71 (s, 1H), 7.88 (d, J = 7.7 Hz, 2H),
		7.46 (d, J = 2.3 Hz, 4H), 7.36 (d, J = 8.1 Hz, 2H), 7.15 (d,
		J = 8.1 Hz, 2H), 5.14 (s, 2H), 3.57 (s, 1H), 3.33 (s, 3H),
		3.21 (d, J = 2.5 Hz, 2H), 1.74 (s, 2H), 1.46 (d, J = 6.0 Hz,
		6H).
282	tert-butyl piperazine- 1-carboxylate
		Compound 282: (4-chlorophenyl)methyl N-(4-{2-[4-
		(2,2-difluoroethyl)piperazin-1-yl]-2-
		oxoethyl}phenyl)carbamate. LCMS-ES (Pos) m/z: 452
		[M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H),
		7.46 (d, J = 2.5 Hz, 4H), 7.39 (d, J = 8.0 Hz, 2H), 7.12
		(d, J = 8.2 Hz, 2H), 6.17 (m, 1H), 5.14 (s, 2H), 3.44 (m,
		8H), 3.63 (s, 2H), 2.80 (d, J = 18.4 Hz, 1H), 2.72 (s, 1H).
283	4-methoxypiperidine
		Compound 283: (4-chlorophenyl)methyl N-{4-[2-(4-
		methoxypiperidin-1-yl)-2-oxoethyl]phenyl}carbamate.
		LCMS-ES (Pos) m/z: 417 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 9.74 (s, 1H), 7.46 (s, 4H), 7.39 (d, J = 8.2 Hz,
		2H), 7.13 (d, J = 8.2 Hz, 2H), 5.14 (s, 2H), 3.90-3.73 (m,
		1H), 3.67 (s, 3H), 3.32 (s, 2H), 3.20-3.12 (m, 1H), 3.06
		(td, J = 10.0, 9.3, 5.1 Hz, 1H), 2.70 (d, J = 1.3 Hz, 2H),
		1.84-1.56 (m, 2H), 1.38-1.02 (m, 2H).
287	(2R)-2- piperidinemethanoL
		Compound 287: (4-chlorophenyl)methyl N-(4-{2-
		[(2R)-2-(hydroxymethyl)piperidin-1-yl]-2-
		oxoethyl}phenyl)carbamate.
		LCMS-ES (Pos) m/z: 417 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 9.74 (s, 1H), 7.46 (d, J = 2.3 Hz, 4H), 7.39
		(d, J = 8.1 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 5.14 (s, 2H),
		4.83 (s, 1H), 4.53 (s, 1H), 4.35 (d, J = 13.9 Hz, 1H), 3.97
		(s, 1H), 3.73 (dd, J = 33.2, 14.4 Hz, 1H), 3.62 (s, 2H), 3.55
		(d, J = 16.3 Hz, 1H), 3.46 (s, 1H), 1.59 (s, 1H), 1.46 (s,
		2H) 1.24 (m, 2H).
300	(pyrazin-2- ylmethyl)amine
		Compound 300: (4-chlorophenyl)methyl N-(4-
		{[(pyrazin-2-
		ylmethyl)carbamoyl]methyl}phenyl)carbamate
		LCMS-ES (Pos) m/z: 411 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 9.74 (s, 1H), 8.66 (s, 1H), 8.58 (s, 1H), 8.51
		(d, J = 10.0 Hz, 2H), 7.46 (s, 4H), 7.39 (d, J = 7.9 Hz,
		2H), 7.19 (d, J = 8.1 Hz, 2H), 5.14 (s, 2H), 4.41 (d, J =
		5.8 Hz, 2H), 3.44 (s, 2H).
308	4- aminotetrahydropyran
		Compound 308: (4-chlorophenyl)methyl N-(4-{[(oxan-
		4-yl)carbamoyl]methyl}phenyl)carbamate LCMS-ES
		(Pos) m/z: 403 (M + H). 1H NMR (400 MHz, Chloroform-
		d) δ 7.29 (d, J = 6.8 Hz, 4H), 7.19 (s, 3H), 7.12 (d, J =
		8.1 Hz, 2H), 6.61 (s, 1H), 5.10 (s, 2H), 3.81 (d, J = 12.2
		Hz, 1H), 3.45 (s, 2H), 3.36 (t, J = 11.6 Hz, 2H), 1.53 (s,
		4H), 1.34-1.16 (m, 2H).
317	(R)-(+)-3- hydroxypyrrolidine
		Compound 317: (4-chlorophenyl)methyl N-(4-{2-
		[(3R)-3-hydroxypyrrolidin-1-yl]-2-
		oxoethyl}phenyl)carbamate LCMS-ES (Pos) m/z: 389
		[M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
		7.46 (s, 4H), 7.38 (d, J = 8.1 Hz, 2H), 7.13 (d, J = 8.1 Hz,
		2H), 5.14 (s, 2H), 4.99 (s, 1H), 4.23 (s, 1H), 3.33 (m,
		5H), 3.31-3.21 (m, 1H), 1.82 (m, 1H), 1.73 (s, 1H).
319	(S)-(−)-3- hydroxypyrrolidine
		Compound 319: (4- chlorophenyl)methyl N-(4-{2-
		[(3S)-3-hydroxypyrrolidin-1-yl]-2-
		oxoethyl}phenyl)carbamate. LCMS-ES (Pos) m/z: 389
		[M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H),
		7.46 (s, 4H), 7.38 (d, J = 8.1 Hz, 2H), 7.13 (d, J = 8.1 Hz,
		2H), 5.14 (s, 2H), 4.99 (s, 1H), 4.89 (s, 1H), 4.29 (s, 1H),
		4.23 (s, 1H), 3.33 (s, 5H), 3.31-3.21 (m, 1H), 1.73 (s,
		1H). 1H NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H), 7.46
		(s, 4H), 7.38 (d, J = 8.1 Hz, 2H), 7.13 (d, J = 8.1 Hz,
		2H), 5.14 (s, 2H), 4.99 (s, 1H), 4.23 (s, 1H), 3.33 (m,
		5H), 3.31-3.21 (m, 1H), 1.82 (m, 1H), 1.73 (s, 1H).
323	(6-methyl-3- pyridinyl)methylamine
		Compound 323: (4-chlorophenyl)methyl N-[4-({[(6-
		methylpyridin-3-
		yl)methyl]carbamoyl}methyl)phenyl]carbamate.
		LCMS-ES (Pos) m/z: 424 [M + H]+. 1H NMR (400 MHz,
		Methanol-d4) δ 9.33 (s, 1H), 8.61 (d, J = 6.4 Hz, 1H), 8.46
		(s, 1H), 8.28 (dd, J = 8.3, 1.9 Hz, 1H), 7.81 (d, J = 8.3 Hz,
		1H), 7.37 (t, J = 7.5 Hz, 6H), 7.20 (d, J = 8.1 Hz, 2H), 5.15
		(s, 2H), 4.48 (d, J = 4.6 Hz, 2H), 3.52 (s, 2H), 2.72 (s, 3H).
332	1-methyl-2- piperazinone
		Compound 332: (4-chlorophenyl)methyl N-{4-[2-(4-
		methyl-3-oxopiperazin-1-yl)-2-
		oxoethyl]phenyl}carbamate
		LCMS-ES (Pos) m/z: 416 [M + H]+. 1H NMR (400 MHz,
		DMSO-d6) δ 9.75 (s, 1H), 7.46 (s, 4H), 7.39 (d, J = 8.1 Hz,
		2H), 7.13 (dd, J = 13.4, 8.2 Hz, 2H), 5.76 (d, J = 1.3 Hz,
		1H), 5.14 (s, 2H), 3.99 (s, 1H), 3.78-3.56 (m, 3H), 3.28
		(d, J = 5.8 Hz, 1H), 3.21-3.09 (m, 1H), 2.84 (d, J = 4.9
		Hz, 1H), 1.26 (q, J = 7.3, 6.6 Hz, 3H).
338	(1R,4R)-4- (trifluoromethoxy) cyclohexan-1-amine
		Compound 338: (4-chlorophenyl)methyl N-[4-
		({[(1r,4r)-4-
		(trifluoromethoxy)cyclohexyl]carbamoyl}methyl)phenyl]
		carbamate LCMS-ES (Pos) m/z: 485 [M + H]+. 1H
		NMR (400 MHz, DMSO-d6) δ 9.72 (s, 1H), 7.94 (d, J =
		7.5 Hz, 1H), 7.46 (d, J = 2.6 Hz, 4H), 7.36 (d, J = 8.1 Hz,
		2H), 7.14 (d, J = 8.0 Hz, 2H), 5.14 (s, 2H), 4.37 (s, 1H),
		3.36 (s, 2H), 3.30 (s, 1H), 2.03-1.94 (m, 2H), 1.85-1.76
		(m, 2H), 1.55 (q, J = 12.0 Hz, 2H), 1.31 (q, J = 12.3 Hz,
		2H).
264	N,6-dimethylpyridin- 3-amine
		Compound 264: (4-chlorophenyl)methyl N-(4-
		{[methyl(6-methylpyridin-3-
		yl)carbamoyl]methyl}phenyl)carbamate. LCMS-APCI
		(POS.) m/z: 424.1 [M + H]+. 1H NMR (400 MHz, 60° C.,
		Methanol-d6) δ 8.25 (s, 1H), 7.58 (d, J = 8.1 Hz, 1H), 7.43-
		7.27 (m, 7H), 6.94 (s, 2H), 5.15 (s, 2H), 3.52 (bs, 2H),
		3.27 (s, 3H), 2.56 (d, J = 1.9 Hz, 3H).
178	2-methyl-2,5- diazabicyclo[4.1.0] heptane
		Compound 178: 4-chlorobenzyl (4-(2-(5-methyl-2,5-
		diazabicyclo[4.1.0]heptan-2-yl)-2-
		oxoethyl)phenyl)carbamate. LCMS-APCI (POS.) m/z:
		414 [M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 9.73 (s,
		1H), 7.46 (m, 4H), 7.39 (d, J = 8.1 Hz, 2H), 7.13 (dd, J =
		18.3, 8.1 Hz, 2H), 5.14 (s, 2H), 4.05-3.60 (m, 2H), 3.32 (s,
		3H), 2.96 (d, J = 9.9 Hz, 1H), 2.61 (s, 2H), 2.35-2.26 (m,
		2H), 2.03 (t, J = 10.9 Hz, 1H), 1.24 (s, 1H), 0.63 (m, 1H).
273	5-fluoropyridin-3- amine
		Compound 273: (4-chlorophenyl)methyl N-(4-{[(5-
		fluoropyridin-3-
		yl)carbamoyl]methyl}phenyl)carbamate. LCMS-APCI
		(POS.) m/z: 414.0 [M + H]+. 1H NMR (400 MHz, DMSO-
		d6) δ 10.60 (s, 1H), 9.76 (s, 1H), 8.53 (s, 1H), 8.26 (s, 1H),
		8.05 (d, J = 11.4 Hz, 1H), 7.49-7.44 (m, 4H), 7.41 (d, J =
		8.1 Hz, 2H), 7.23 (d, J = 8.2 Hz, 2H), 5.13 (s, 2H), 3.62 (s,
		2H).
312	2-piperazinone
		Compound 312: (4-chlorophenyl)methyl N-{4-[1,1-
		difluoro-2-oxo-2-(3-oxopiperazin-1-
		yl)ethyl]phenyl}carbamate. LCMS-ES (Pos) m/z: 438
		[M + H]+. 1H NMR (400 MHz, Methanol-d4) δ 7.62 (d, J =
		8.4 Hz, 2H), 7.49 (d, J = 7.9 Hz, 2H), 7.39 (q, J = 8.2 Hz,
		4H), 5.17 (s, 2H), 4.23 (s, 1H), 4.06 (s, 1H), 3.87 (s, 1H),
		3.66 (s, 1H), 3.09 (s, 2H).

Example P

Preparation of (4-chlorophenyl)methyl N-{4-[(3-methyl-1,2,4-oxadiazol-5-yl)methyl]phenyl}carbamate (Compound 344)

To a solution of [4-({[(4-chlorophenyl)methoxy]carbonyl}amino)phenyl]acetic acid (148 mg, 0.46 mmol) and N,N-diisopropylethylamine (0.32 mL, 1.85 mmol) in DMF (1.5 mL) was added (Z)—N′-hydroxyethanimidamide (44.6 mg, 0.60 mmol) and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (228.8 mg, 0.60 mmol). The mixture was stirred at rt for 1.5 h, diluted with water, saturated sodium bicarbonate, and extracted with DCM. The combined organic layers were dried over sodium sulfate, concentrated, and used without further purification. To a crude solution of (Z)-(1-aminoethylidene)amino 2-[4-({[(4-chlorophenyl)methoxy]carbonyl}amino)phenyl]acetate (173.9 mg, 0.46 mmol) in THF (3 mL) was added DBU (0.21 mL, 1.39 mmol). The mixture was stirred at 50° C. for 16 h, cooled, filtered, and purified by reverse phase prep HPLC using a gradient of 3-40% water/acetonitrile with 0.1% formic acid to yield product (4-chlorophenyl)methyl N-{4-[(3-methyl-1,2,4-oxadiazol-5-yl)methyl]phenyl}carbamate (13 mg, 0.04 mmol, 8% yield) over 2 steps. LCMS-APCI (POS.) m/z: 358.4 [M+H]⁺. ¹H NMR (400 MHz, DMSO-d₆) δ 9.80 (s, 1H), 7.49-7.44 (m, 4H), 7.43 (d, J=7.6 Hz, 2H), 7.23 (d, J=8.0 Hz, 2H), 5.13 (s, 2H), 4.21 (s, 2H), 2.29 (d, J=2.4 Hz, 3H).

LHS Sulfonamide Synthesis

Example Q

Preparation of 4-chlorobenzyl (4-(N-methyl-N-(oxetan-3-yl)sulfamoyl)phenyl)carbamate (Compound 352)

A mixture of (4-chlorophenyl)methyl N-[4-(chlorosulfonyl)phenyl]carbamate (50 mg, 0.14 mmol, 1.0 eqiv), triethylamine (0.028 g, 0.27 mmol, 2.0 eq), and amine (1.5 eqiv) was stirred in DCM (1 mL) for 30 min. The reaction mixture was concentrated, resuspended in MeOH, and purified on reverse phase HPLC eluted with 0-95% acetonitrile:water w/0.1% formic acid) to give the desired product LCMS-APCI (POS.) m/z: 411.1 [M+H]⁺. 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 7.68 (s, 4H), 7.47 (d, J=2.1 Hz, 4H), 5.18 (s, 2H), 4.54 (s, 4H), 3.17 (d, J=5.2 Hz, 1H), 2.66 (s, 3H).

Compounds in the following table were prepared in a similar manner as Compound 352, using the intermediate 22.1 and amine as listed.

Co
#	amine	Structure, Name and Data
335	N-methyl-1- phenylmethanamine	Compound 335: 4-chlorobenzyl (4-(N-benzyl-N- methylsulfamoyl)phenyl)carbamate. LCMS-APCI (POS.) m/z: 444.0 [M + H]+. 1H NMR (400 MHZ, DMSO-d6) δ 10.32 (s, 1H), 7.80-7.69 (m, 4H), 7.48 (s, 4H), 7.36 (d, J = 7.0 Hz, 2H), 7.30 (d, J = 7.7 Hz, 3H), 5.19 (s, 2H), 4.08 (s, 2H).
337	(R)-N- methyltetrahydrofuran- 3-amine	Compound 337: 4-chlorobenzyl (R)-(4-(N-methyl-N- (tetrahydrofuran-3-yl)sulfamoyl)phenyl)carbamate. LCMS-APCI (POS.) m/z: 427.0 [M + H]+. 1H NMR (400 MHZ, DMSO-d6) δ 10.31 (s, 1H), 7.70 (q, J = 8.5 Hz, 4H), 7.47 (d, J = 1.9 Hz, 4H), 5.18 (s, 2H), 4.50 (s, 2H), 3.75 (s, 2H), 2.61 (d, J = 1.7 Hz, 3H), 1.88 (s, 2H), 1.49 (s, 1H).
342	N-methyltetrahydrofuran- 3-amine	Compound 342: 4-chlorobenzyl (4-(N- methyl-N-(tetrahydrofuran-3- yl)sulfamoyl)phenyl)carbamate. LCMS-APCI (POS.) m/z: 424.1 [M + H]+. 1H NMR (400 MHZ, DMSO-d6) δ 10.31 (s, 1H), 7.70 (q, J = 8.7 Hz, 4H), 7.48 (d, J = 2.0 Hz, 4H), 5.19 (s, 2H), 4.50 (s, 2H), 3.76 (s, 2H), 2.62 (s, 3H), 1.87 (s, 1H), 1.50 (s, 1H).

Example R

Preparation of oxazol-5-ylmethyl (4-((1-(dimethylcarbamoyl)piperidin-4-yl)methyl)phenyl)carbamate (Compound 30)

Step 1: Preparation of tert-butyl 4-(4-(((oxazol-5-ylmethoxy)carbonyl)amino)benzyl)piperidine-1l-carboxylate

To a solution of triphosgene (2.38 g, 8.0 mmol) in DCM (100 mL) at 0° C. was added a mixture of tert-butyl 4-(4-aminobenzyl)piperidine-1-carboxylate (5.81 g, 20.0 mmol), DIEA (5.68 g, 44.0 mmol), DMAP (2.22 g, 20.0 mmol) in DCM (100 mL). The mixture was stirred at 0° C. for 5 min and oxazol-5-ylmethanol (2.58 g, 26.0 mmol) was added. The resulting mixture was stirred at 24° C. for 1 h and concentrated. The residue was purified by silica gel chromatography eluted with EtOAc/Hexane (1:1) to afford the desired product (7.1 g, 85.4%) as a white solid. LRMS (ES) 416.1 [M+H]⁺.

Step 2: Preparation of oxazol-5-ylmethyl (4-(piperidin-4-ylmethyl)phenyl)carbamate hydrochloride

To a mixture of tert-butyl 4-(4-(((oxazol-5-ylmethoxy)carbonyl)amino)benzyl)piperidine-1-carboxylate (7.1 g, 17.1 mmol) in MeOH (10 mL) was added 4M HCl/dioxane (36 mL, 144 mmol). The reaction mixture was stirred at 24° C. for 2 h and concentrated to dryness to afford the crude product as a white solid (6.01 g, 100%). LRMS (m/z): 316.1 [M+H]⁺.

Step 3: Preparation of oxazol-5-ylmethyl (4-((1-(dimethylcarbamoyl)piperidin-4-yl)methyl)phenyl)carbamate

To a mixture of oxazol-5-ylmethyl (4-(piperidin-4-ylmethyl)phenyl)carbamate hydrochloride (1.97 g, 5.6 mmol), and DIEA (1.81 g, 14.0 mmol) in DCM at 0° C. was added dimethylcarbamoyl chloride (0.66 g, 6.16 mmol) dropwise. The reaction mixture was warmed to 24° C. and stirred for 1 h. The mixture was concentrated and the residue was purified by silica gel chromatography eluted with EtOAc to afford the desired product (1.66 g, 76.7%) as a white solid. LRMS (m/z): 387.1 [M+H]⁺. ¹H NMR (400 MHz, Methanol-d₄) δ 8.24 (s, 1H), 7.35 (d, J=8.0 Hz, 2H), 7.25 (s, 1H), 7.18-6.98 (m, 2H), 5.24 (s, 2H), 3.64 (d, J=13.0 Hz, 2H), 2.82 (d, J=1.4 Hz, 6H), 2.72 (td, J=12.8, 2.3 Hz, 2H), 2.52 (d, J=6.9 Hz, 2H), 1.76-1.56 (m, 3H), 1.28-1.12 (m, 2H).

Example S

Preparation of oxazol-5-ylmethyl (R)-(4-(1-(dimethylcarbamoyl)piperidin-3-yl)phenyl)carbamate (Compound 376)

Step 1: Preparation of tert-butyl (R)-3-(4-(((oxazol-5-ylmethoxy)carbonyl)amino)phenyl)piperidine-1-carboxylate

To a mixture of triphosgene (0.715 g, 2.41 mmol) in 60 mL acetonitrile at 0° C. was added a mixture of tert-butyl (R)-3-(4-aminophenyl)piperidine-1-carboxylate (2.00 g, 7.24 mmol) and N,N-diisopropylethylamine (1.87 g, 14.47 mmol) in 40 mL MeCN. The mixture was stirred at 0° C. for 15 min, warmed to 24° C., followed by addition of a mixture of DMAP (44 mg, 0.362 mmol, 0.05 equiv) and 1,3-oxazol-5-ylmethanol (790 mg, 8.00 mmol) in MeCN (10 mL). The mixture was stirred at 24° C. for 16 h and at 50° C. for 1 h. The reaction mixture was cooled and concentrated. The mixture was dissolved in 150 mL dichloromethane, washed with 0.5 N HCl, brine, dried (Na₂SO₄) and concentrated to afford the crude product (2.91 g) as an off-white foam that was used in the next reaction without further purification. LRMS (ES) 402.2 [M+H]⁺.

Step 2: Preparation of oxazol-5-ylmethyl (R)-(4-(piperidin-3-yl)phenyl)carbamate hydrochloride

To a mixture of tert-butyl (R)-3-(4-(((oxazol-5-ylmethoxy)carbonyl)amino)phenyl)piperidine-1-carboxylate (2.90 g, 7.20 mmol) in THF (36 mL) was added 4M HCl/dioxane (36 mL, 144 mmol). The reaction mixture was stirred at 24° C. for 16 h, filtered, washed with EtOAc (2×30 mL) to give the crude product as an off-white solid in quantitative yield. LRMS (m/z): 302.1 [M+H]⁺.

Step 3: Preparation of oxazol-5-ylmethyl (R)-(4-(1-(dimethylcarbamoyl)piperidin-3-yl)phenyl)carbamate

To a mixture of (3R)-3-(4-{[(1,3-oxazol-5-ylmethoxy)carbonyl]amino}phenyl)piperidin-1-ium chloride (243 mg, 0.72 mmol, 1 equiv), N,N-diisopropylethylamine (0.5 mL, 2.88 mmol, 4 equiv) and DCM (5 mL) was added dimethylcarbamyl chloride (1.17 mmol) dropwise, the mixture was stirred at 24° C. for 2 h, diluted with 5 mL DCM, washed with 0.5 N HCl, saturated NaHCO₃, and brine, dried (Na₂SO₄), and concentrated. The residue was purified by Prep-HPLC with the following conditions (Column: XBridge Prep OBD C18 Column 30×150 mm 5 um; Mobile Phase A:Water (0.1% formic acid), Mobile Phase B: MeCN (0.1% formic acid; Flow rate: 20 mL/min) to afford oxazol-5-ylmethyl (R)-(4-(1-(dimethylcarbamoyl)piperidin-3-yl)phenyl)carbamate (0.15 g, 56%) as a white solid. LRMS (m/z): 373.1 [M+H]⁺. ¹H NMR (400 MHz, DMSO-d₆) δ 9.76 (s, 1H), 8.43 (s, 1H), 7.38 (d, J=8.1 Hz, 2H), 7.31 (s, 1H), 7.18 (d, J=8.5 Hz, 2H), 5.21 (s, 2H), 3.55 (dd, J=22.5, 12.0 Hz, 2H), 2.73 (s, 6H), 2.74-2.66 (m, 2H), 2.64 (d, J=12.0 Hz, 1H), 1.87 (d, J=11.0 Hz, 1H),

Example T

Preparation of oxazol-5-ylmethyl (4-(1-isobutyrylpiperidin-4-yl)phenyl)carbamate (Compound 7)

Step 1: Preparation of tert-butyl 4-(4-(((oxazol-5-ylmethoxy)carbonyl)amino)phenyl)piperidine-1-carboxylate

To a mixture of triphosgene (1.48 g, 5.00 mmol) in 150 mL of acetonitrile at 0° C. was added a mixture of tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate (4.15 g, 15.0 mmol) and N,N-diisopropylethylamine (3.88 g, 30.0 mmol) in 100 mL acetonitrile The mixture was stirred at 0° C. for 15 min, then warmed to 24° C., followed by addition of a mixture of DMAP (92 mg, 0.75 mmol) and 1,3-oxazol-5-ylmethanol (1.82 g, 18.0 mmol) in MeCN (25 mL). The mixture was stirred at 24° C. for 16 h, then at 50° C. for 1 h. then concentrated. The mixture was dissolved in 350 mL dichloromethane, washed with 0.5 N HCl, brine, dried (Na₂SO₄) and concentrated to afford the crude product (6.00 g) as an off-white foam that was used in the next reaction without further purification. LRMS (ES) 402.2 [M+H]⁺.

Step 2: Preparation of oxazol-5-ylmethyl (4-(piperidin-4-yl)phenyl)carbamate hydrochloride

To a mixture of tert-butyl 4-(4-(((oxazol-5-ylmethoxy)carbonyl)amino)phenyl)piperidine-1-carboxylate (5.80 g, 14.4 mmol) in THF (72 mL) was added 4M HCl/dioxane (72 mL, 288 mmol). The reaction mixture was stirred at 24° C. for 16 h, filtered, and washed with EtOAc (2×60 mL) to give the desired crude product which was obtained as an off-white solid in quantitative yield. LRMS (m/z): 302.1 [M+H]⁺.

Step 3: Preparation of oxazol-5-ylmethyl (4-(1-isobutyrylpiperidin-4-yl)phenyl)carbamate

To a mixture of oxazol-5-ylmethyl (4-(piperidin-4-yl)phenyl)carbamate hydrochloride (0.74 mmol) and N,N-diisopropylethylamine (05 mL, 2.88 mmol) in dichloromethane (5 mL) was added isobutyl chloride (0.095 g, 0.89 mmol) dropwise. The mixture was allowed to stir at 24° C. for 2 h. diluted with 5 mL DCM, washed with 0.5 N HCl, saturated NaHCO₃, and brine respectively, dried (Na₂SO₄), and concentrated. The residue was purified by Prep-HPLC with the following conditions (Column: XBridge Prep OBD C18 Column 30×150 mm 5 um; Mobile Phase A:Water (0.1% formic acid), Mobile Phase B: MeCN (0.1% formic acid; Flow rate: 20 mL/min) to afford oxazol-5-ylmethyl (4-(1-isobutyrylpiperidin-4-yl)phenyl)carbamate (0.15 g, 55%) as a white solid. LRMS (m/z): 372.1 [M+H]⁺. ¹H NMR (400 MHz, DMSO-d₆) δ 9.73 (s, 1H), 8.42 (s, 1H), 7.37 (d, J=8.1 Hz, 2H), 7.30 (s, 1H), 7.16 (d, J=8.5 Hz, 2H), 5.21 (s, 2H), 4.55 (d, J=12.8 Hz, 1H), 4.05 (d, J=13.4 Hz, 1H), 3.09 (t, J=12.9 Hz, 1H), 2.90 (p, J=6.7 Hz, 1H), 2.69 (d, J=12.1 Hz, 1H), 2.58 (d, J=12.7 Hz, 1H), 1.78 (t, J=17.1 Hz, 2H), 1.52-1.34 (m, 2H), 1.01 (d, J=6.6 Hz, 6H).

Synthesis of Comparator Ureas

Example U

Preparation of 1-(4-chlorobenzyl)-3-(4-((1-(oxetan-3-yl)piperidin-4-yl)methyl)phenyl)urea (Comparator 1)

Step 1: Preparation of tert-butyl 4-(4-(3-(4-chlorobenzyl)ureido)benzyl)piperidine-1-carboxylate

A mixture of tert-butyl 4-(4-aminobenzyl)piperidine-1-carboxylate (0.55 g, 1 equiv) and 1-chloro-4-(isocyanatomethyl)benzene (1.5 equiv) in DCM (3 mL) was stirred at 24° C. for 1 h, and purified by silica gel chromatography (50% EtOAc/Hexanes) to afford tert-butyl 4-(4-(3-(4-chlorobenzyl)ureido)benzyl)piperidine-1-carboxylate (0.84 g, 96.8% yield). LRMS (ES) 403.1 288.1 [M+H-Bu]⁺.

Step 2: Preparation of 1-(4-chlorobenzyl)-3-(4-(piperidin-4-ylmethyl)phenyl)urea hydrochloride

To a mixture of tert-butyl 4-(4-(3-(4-chlorobenzyl)ureido)benzyl)piperidine-1-carboxylate (0.84 g, 1 equiv) in MeOH (1 mL) at 0° C., was added 4 M HCl in dioxane (12 equiv), the mixture was stirred at 24° C. for 1 h and concentrated to afford 1-(4-chlorobenzyl)-3-(4-(piperidin-4-ylmethyl)phenyl)urea hydrochloride (0.72 g, 99.6% yield) that was used in the next reaction without further purification. LRMS (ES) 358.1 [M+H].

equivequiv

Step 3: Preparation of 1-(4-chlorobenzyl)-3-(4-((1-(oxetan-3-yl)piperidin-4-yl)methyl)phenyl)urea

To a mixture of 1-(4-chlorobenzyl)-3-(4-(piperidin-4-ylmethyl)phenyl)urea hydrochloride (0.47 g, 1 equiv) and oxetan-3-one (2 equiv) in DCM (3 mL) was added Na(OAc)₃BH (2.2 equiv) and DIPEA (1 equiv). The reaction mixture was stirred at 24° C. for 16 hours, quenched with saturated NaHCO₃(5 mL), extracted with DCM (5 mL) twice. equivequivequivequiv The organic layer was combined, concentrated, and purified on HPLC (10% AcCN) to afford 1-(4-chlorobenzyl)-3-(4-((1-(oxetan-3-yl)piperidin-4-yl)methyl)phenyl)urea (0.27 g, 53.3% yield). LRMS (ES) 414.1 [M+H]. ¹H NMR (400 MHz, DMSO-d₆) δ 8.48 (s, 1H), 7.39 (d, J=8.5 Hz, 2H), 7.31 (d, J=8.4 Hz, 2H), 7.29 (d, J=8.3 Hz, 2H), 7.00 (d, J=8.3 Hz, 2H), 6.59 (t, J=6.0 Hz, 1H), 4.49 (t, J=6.4 Hz, 2H), 4.38 (t, J=6.1 Hz, 2H), 4.27 (d, J=6.0 Hz, 2H), 3.30 (p, J=6.5 Hz, 1H), 2.63 (d, J=11.0 Hz, 2H), 2.41 (d, J=6.9 Hz, 2H), 1.64 (t, J=11.2 Hz, 2H), 1.53 (d, J=11.4 Hz, 2H), 1.48-1.35 (m, 1H), 1.15 (qd, J=12.1, 3.7 Hz, 2H).

Compounds in the following table were prepared in a similar manner as Comparator 1, using the intermediates with alkylation/acylation reagents and methods as listed.

	Alkylation/
	acylation
Aniline	Reagent	Structure, Name and Data
4-(4- aminobenzyl)piperidine- 1-carboxylate	acetic anhydride	Comparator 2: 1-(4-((1-acetylpiperidin-4- yl)methyl)phenyl)-3-(4-chlorobenzyl)urea (0.23 g, 71.9% yield). LRMS (ES) 400.1 [M + H]. 1H NMR (400 MHz, Methanol-d4) δ 7.42-7.20 (m, 6H), 7.19-7.00 (m, 2H), 4.49 (d, J = 13.1 Hz, 1H), 4.38 (s, 2H), 3.89 (d, J = 13.8 Hz, 1H), 3.05 (t, J = 13.3 Hz, 1H), 2.64- 2.44 (m, 3H), 2.09 (s, 3H), 1.88-1.62 (m, 3H), 1.26- 1.02 (m, 2H).
tert-butyl 4-((4- aminobenzyl)oxy) piperidine- 1-carboxylate	oxetan-3-one	Comparator 3: 1-(4-chlorobenzy1)-3-(4-(((1- (oxetan-3-yl)piperidin-4-yl)oxy)methyl)phenyl)urea. LRMS (ES) 430.1 [M + H], 1H NMR (400 MHZ, Methanol-d4) δ 7.39 (d, J = 8.2 Hz, 2H), 7.32 (s, 4H), 7.27 (d, J = 8.2 Hz, 2H), 4.88-4.72 (m, 4H), 4.49 (s, 2H), 4.37 (s, 2H), 4.24 (p, J = 6.6 Hz, 1H), 3.73 (tt, J = 6.1, 3.3 Hz, 1H), 3.20-3.04 (m, 2H), 3.04-2.89 (m, 2H), 2.19-1.61 (m, 4H).

Example V

Preparation of 1-(oxazol-5-ylmethyl)-3-(4-((1-(oxetan-3-yl)piperidin-4-yl)methyl)phenyl)urea (Comparator 4)

Step 1: Preparation of tert-butyl 4-(4-isocyanatobenzyl)piperidine-1-carboxylate

A mixture of tert-butyl 4-(4-aminobenzyl)piperidine-1-carboxylate (2.4 g, 1 equiv) and sat. NaHCO₃ in DCM (50 mL) was stirred at 0° C. Triphosgene (0.33 equiv) in DCM (10 mL) was added and the mixture was stirred for 15 minutes at 0° C. The organic layer was dried to afford tert-butyl 4-(4-isocyanatobenzyl)piperidine-1-carboxylate and was used in the next reaction without further purification.

Step 2: Preparation of tert-butyl 4-(4-(3-(oxazol-5-ylmethyl)ureido)benzyl)piperidine-1-carboxylate

To a mixture of tert-butyl 4-(4-isocyanatobenzyl)piperidine-1-carboxylate (2.6 g, 1 equiv) in DCM was added oxazol-5-ylmethanamine hydrochloride (1.5 equiv) and DIPEA (1.5 equiv). The mixture was stirred at 24° C. for 1 h, washed with 1 N HCl, brine and dried over Na₂SO₄ and concentrated to afford tert-butyl 4-(4-(3-(oxazol-5-ylmethyl)ureido)benzyl)piperidine-1-carboxylate. LRMS (ES) 359.1 [M+H].

Step 3: Preparation of 1-(oxazol-5-ylmethyl)-3-(4-(piperidin-4-ylmethyl)phenyl)urea hydrochloride

A mixture of tert-butyl 4-(4-(3-(oxazol-5-ylmethyl)ureido)benzyl)piperidine-1-carboxylate in MeOH was cooled to 0° C., followed by the addition of 4 M HCl in dioxane (12 equiv), stirring at 24° C. for 1 h, and concentration to afford 1-(oxazol-5-ylmethyl)-3-(4-(piperidin-4-ylmethyl)phenyl)urea hydrochloride and was used in the next reaction without further purification. LRMS (ES) 315.1 [M+H].

Step 4: Preparation of 1-(oxazol-5-ylmethyl)-3-(4-((1-(oxetan-3-yl)piperidin-4-yl)methyl)phenyl)urea

A mixture of 1-(oxazol-5-ylmethyl)-3-(4-(piperidin-4-ylmethyl)phenyl)urea hydrochloride (150 mg, 1 equiv) and oxetan-3-one (1 equiv) in DMF (1 mL) was stirred at 24° C. for 20 minutes. Sodium triacetoxyborohydride (2.2 equiv) was added and the mixture was stirred for 1 h. The mixture was filtered and purified by prep HPLC to afford 1-(oxazol-5-ylmethyl)-3-(4-((1-(oxetan-3-yl)piperidin-4-yl)methyl)phenyl)urea (49 mg, 31% yield). LRMS (ES) 371.1 [M+H]. ¹H NMR (400 MHz, DMSO-d₆) δ 8.46 (s, 1H), 7.27 (d, J=8.0 Hz, 2H), 7.00 (d, J=7.7 Hz, 3H), 6.55 (t, J=5.9 Hz, 1H), 4.48 (t, J=6.5 Hz, 2H), 4.43-4.29 (m, 4H), 3.29 (d, J=7.5 Hz, 1H), 2.62 (d, J=11.1 Hz, 2H), 2.41 (d, J=6.9 Hz, 2H), 1.64 (t, J=11.4 Hz, 2H), 1.52 (d, J=12.9 Hz, 2H), 1.41 (s, 1H), 1.16 (t, J=11.9 Hz, 2H).

Compounds in the following table were prepared in a similar manner as Comparator 4, using the intermediates with alkylation/acylation reagents and methods as listed.

	Amine capped
Aniline	reagent	Structure, Name and Data
4-(4- aminobenzyl)piperidine- 1-carboxylate	acetic anhydride	Comparator 5: 1-(4-((1-acetylpiperidin-4- yl)methyl)phenyl)-3-(oxazol-5- ylmethyl)urea. LRMS (ES) 357.1 [M + H]. 1H NMR (400 MHZ, DMSO- d6) δ 8.46 (s, 1H), 8.28 (s, 1H), 7.29 (d, J = 7.8 Hz, 2H), 7.05-6.96 (m, 3H), 6.55 (s, 1H), 4.40-4.27 (m, 3H), 3.75 (d, J = 13.6 Hz, 1H), 2.92 (t, J = 12.9 Hz, 1H), 2.43 (t, J = 9.2 Hz, 3H), 1.95 (s, 3H), 1.67 (s, 1H), 1.55 (t, J = 12.8 Hz, 2H), 1.01 (dt, J = 50.0, 12.6 Hz, 2H).
4-(4- aminobenzyl)piperidine- 1-carboxylate	dimethylcarbamoyl chloride	Comparator 6: N,N-dimethyl-4-(4-(3-(oxazol-5- ylmethyl)ureido)benzyl)piperidine- 1-carboxamide. LRMS (ES) 386.1 [M + H]. 1H NMR (400 MHZ, DMSO- d6) δ 8.46 (s, 1H), 8.27 (s, 1H), 7.28 (d, J = 8.0 Hz, 2H), 7.00 (d, J = 7.9, 4.8 Hz, 3H), 6.57 (s, 1H), 4.35 (d, J = 5.8 Hz, 2H), 3.49 (d, J = 13.3 Hz, 2H), 2.69 (s, 6H), 2.58 (t, J = 12.3 Hz, 2H), 2.42 (d, J = 6.9 Hz, 2H), 1.69-1.47 (m, 3H), 1.08 (q, J = 12.1 Hz, 2H).

Biological Example 1

NMN Fluorescence Biochemical Assay

Human Recombinant Enzyme Assay

Compounds described herein were assayed for their ability to stimulate the synthesis of nicotinamide mononucleotide (NMN) by the enzyme NAMPT. The human recombinant enzyme assay measures the activation of the enzyme activity by compounds using recombinant enzyme and substrates in a buffered cell-free system. The assay conditions closely mimic cellular environments. Dose responses were measured using an assay to detect the formation of nicotinamide mono-nucleotide. All experiments were performed in the 384-well format. Generally, 0.5 μL of DMSO containing varying concentrations of the test compound was mixed with 10 μL of the enzyme reagent solution. Enzyme reactions were initiated with the addition of L of a solution containing the substrates. The final assay conditions were as follows: 6 nM human NAMPT, 2.5 mM ATP, 20 μM PRPP and 150 μM nicotinamide in 50 mM HEPES, pH 7.2, 1 mM DTT, 1 mM CHAPS 50 mM NaCl, 100 mM MgCl₂. Following an incubation of 60 min at ambient temperature, 10 μL of 20% acetophenone in DMSO was added, followed by 10 μL of 2 M KOH and 40 μL of formic acid. The plates were read for fluorescence (Excitation/Emission=355 nm/460 nm) using an EnVision plate reader after 40 mins of incubation at ambient temperature. The potency measurements for compounds are quantified and represented as AC_1.4 (the concentration of compounds that generates 40% higher activity over basal) and EC₅₀ (concentration of the compound that gives half-maximal activation). Table A shows the AC_1.4 and EC₅₀ data and for the tested compounds.

TABLE A
Compound	AC1.4	EC50
No.	Human (μM)	Human (μM)
1	0.03	0.44
2	0.05	0.96
3	0.05	0.31
4	0.06	21.81
5	0.07	0.29
6	0.07	0.55
7	0.11	20.81
8	0.14	32.56
9	0.15	16.00
10	0.16	11.19
11	0.21	22.51
12	0.22	0.34
13	0.22	44.66
14	0.23	10.74
15	0.24	2.16
16	0.25	3.50
17	0.25	0.90
18	0.25	16.18
19	0.26	0.59
20	0.29	2.57
21	0.30	2.00
22	0.32	10.08
23	0.32	2.76
24	0.34	1.88
25	0.35	7.80
26	0.35	27.47
27	0.36	5.25
28	0.36	3.01
29	0.37	1.51
30	0.37	25.14
31	0.37	21.68
32	0.38	20.97
33	0.38	1.01
34	0.38	0.82
35	0.39	37.92
36	0.40	1.00
37	0.41	3.67
38	0.42	1.22
39	0.43	19.17
40	0.43	2.40
41	0.44	3.48
42	0.44	5.66
43	0.45	4.56
44	0.45	4.19
45	0.46	1.88
46	0.48	2.58
47	0.49	9.61
48	0.49	31.01
49	0.50	2.02
50	0.50	0.89
51	0.50	40.31
52	0.50	5.38
53	0.51	5.89
54	0.51	8.45
55	0.51	1.82
56	0.53	2.80
57	0.54	1.29
58	0.55	1.73
59	0.56	48.93
60	0.57	1.91
61	0.57	2.62
62	0.57	2.64
63	0.57	4.93
64	0.58	4.22
65	0.58	37.12
66	0.59	5.12
67	0.59	21.33
68	0.59	11.05
69	0.59	3.07
70	0.61	22.95
71	0.61	2.51
72	0.62	5.27
73	0.62	1.76
74	0.64	1.42
75	0.64	26.31
76	0.64	0.89
77	0.65	1.67
78	0.65	7.44
79	0.66	23.59
80	0.66	28.98
81	0.66	3.41
82	0.66	3.90
83	0.66	8.11
84	0.66	3.12
85	0.67	6.38
86	0.68	6.21
87	0.68	1.75
88	0.69	37.44
89	0.71	9.40
90	0.72	7.32
91	0.74	3.80
92	0.75	3.22
93	0.75	6.80
94	0.75	2.36
95	0.75	3.11
96	0.75	3.47
97	0.76	23.61
98	0.78	1.49
99	0.79	51.18
100	0.81	1.22
101	0.82	4.14
102	0.82	1.89
103	0.83	4.31
104	0.85	5.06
105	0.85	1.94
106	0.86	26.38
107	0.89	10.81
108	0.89	8.17
109	0.90	4.71
110	0.91	3.46
111	0.91	5.33
112	0.93	5.53
113	0.94	50.96
114	0.94	19.66
115	0.94	3.13
116	0.95	6.77
117	0.95	8.14
118	0.95	3.13
119	0.95	21.72
120	0.96	44.85
121	0.97	14.49
122	0.97	6.46
123	0.98	5.01
124	0.98	15.29
125	0.98	6.02
126	0.99	4.06
127	1.00	7.30
128	1.03	4.75
129	1.03	2.22
130	1.03	8.13
131	1.05	2.55
132	1.06	41.14
133	1.07	8.60
134	1.07	13.74
135	1.07	3.28
136	1.09	2.23
137	1.11	3.83
138	1.11	8.41
139	1.11	13.06
140	1.15	4.51
141	1.17	2.24
142	1.17	7.35
143	1.18	10.78
144	1.18	7.67
145	1.19	8.23
146	1.20	2.35
147	1.22	5.21
148	1.23	11.53
149	1.23	7.00
150	1.24	4.31
151	1.25	5.89
152	1.27	10.58
153	1.27	33.82
154	1.30	11.95
155	1.31	5.80
156	1.31	9.45
157	1.32	9.11
158	1.32	1.27
159	1.33	4.30
160	1.33	5.32
161	1.33	10.11
162	1.36	4.50
163	1.37	0.68
164	1.38	1.60
165	1.38	7.53
166	1.38	5.87
167	1.39	4.54
168	1.40	13.86
169	1.41	6.11
170	1.41	9.33
171	1.43	9.75
172	1.43	3.54
173	1.46	4.39
174	1.47	28.00
175	1.47	8.92
176	1.47	4.56
177	1.49	38.27
178	1.50	14.72
179	1.50	22.42
180	1.52	15.13
181	1.53	15.60
182	1.54	10.95
183	1.57	15.15
184	1.58	14.88
185	1.59	2.04
186	1.61	3.38
187	1.62	11.25
188	1.62	6.85
189	1.64	18.62
190	1.64	9.00
191	1.69	21.95
192	1.70	6.45
193	1.71	12.71
194	1.73	26.66
195	1.73	8.13
196	1.75	7.22
197	1.75	11.77
198	1.76	8.59
199	1.77	5.28
200	1.78	2.12
201	1.78	26.42
202	1.82	24.46
203	1.82	7.14
204	1.83	21.14
205	1.84	10.06
206	1.85	14.65
207	1.85	9.34
208	1.87	17.36
209	1.88	21.61
210	1.91	3.82
211	1.91	10.57
212	1.93	10.19
213	1.95	2.92
214	1.96	9.59
215	1.96	8.35
216	1.98	5.81
217	1.98	24.43
218	1.99	9.06
219	2.03	20.58
220	2.03	32.47
221	2.04	2.16
222	2.05	27.60
223	2.05	17.62
224	2.08	10.13
225	2.08	9.10
226	2.09	6.14
227	2.11	3.47
228	2.11	21.43
229	2.13	12.84
230	2.13	15.30
231	2.13	33.82
232	2.17	20.77
233	2.18	7.80
234	2.19	3.38
235	2.22	44.87
236	2.25	50.62
237	2.25	32.27
238	2.29	10.63
239	2.32	1.89
240	2.33	2.73
241	2.37	11.77
242	2.38	19.79
243	2.38	26.27
244	2.39	5.67
245	2.39	6.35
246	2.43	6.14
247	2.45	16.53
248	2.51	2.40
249	2.55	15.80
250	2.58	21.30
251	2.59	10.95
252	2.60	26.21
253	2.62	17.89
254	2.64	15.10
255	2.65	31.65
256	2.69	10.52
257	2.70	31.24
258	2.74	7.62
259	2.75	13.87
260	2.77	14.54
261	2.83	9.46
262	2.83	11.87
263	2.92	39.09
264	2.93	19.66
265	2.94	23.23
266	2.98	14.94
267	3.04	36.49
268	3.05	13.78
269	3.13	44.12
270	3.14	47.20
271	3.15	4.80
272	3.18	10.90
273	3.21	14.41
274	3.32	6.15
275	3.32	12.58
276	3.32	18.30
277	3.36	39.88
278	3.40	17.41
279	3.43	29.04
280	3.51	14.48
281	3.56	46.88
282	3.57	19.12
283	3.61	47.93
284	3.72	19.21
285	3.78	9.55
286	3.79	14.18
287	3.81	20.55
288	3.88	3.45
289	3.95	50.31
290	3.95	16.89
291	3.97	38.19
292	4.12	20.01
293	4.16	18.43
294	4.19	46.46
295	4.57	28.03
296	4.62	14.30
297	4.65	19.81
298	4.66	20.45
299	4.67	11.64
300	4.81	26.35
301	4.81	26.79
302	4.86	17.24
303	4.87	19.44
304	4.93	23.54
305	4.95	22.95
306	4.97	13.94
307	5.02	5.55
308	5.08	8.69
309	5.19	14.87
310	5.29	32.75
311	5.40	26.77
312	5.55	39.08
313	5.55	25.57
314	5.75	38.33
315	5.91	7.32
316	6.04	28.62
317	6.19	32.43
318	6.26	56.84
319	6.50	40.75
320	6.60	34.24
321	6.86	55.67
322	7.23	39.27
323	7.41	13.33
324	7.47	50.87
325	7.87	51.06
326	8.05	31.95
327	8.21	21.07
328	8.56	36.33
329	8.65	33.56
330	8.66	46.26
331	8.67	11.86
332	8.89	50.59
333	9.58	38.57
334	9.87	9.33
335	10.05	7.94
336	10.07	24.30
337	10.15	26.38
338	10.44	18.36
339	10.65	45.48
340	10.65	45.63
341	11.08	55.56
342	11.54	11.46
343	11.85	21.90
344	13.04	34.03
345	13.49	20.31
346	13.52	45.34
347	13.92	34.75
348	14.47	35.85
349	15.55	26.02
350	20.27	44.44
351	22.18	37.34
352	22.88	46.27
353	23.63	24.33
354	23.64	38.76
355	25.86	4.96
356	29.04	18.15
357	1.09	39.93
358	0.25	28.93
359	0.104	3.50
360	0.07	2.33
361	0.08	10.84
362	0.05	4.60
363	0.03	4.49
364	0.07	3.97
365	0.33	38.65
366	0.15	10.16
367	0.07	4.77
368	0.09	2.93
369	0.16	4.36
370	0.13	5.80
371	0.27	4.57
372	0.09	5.64
373	0.013	0.24
374	0.08	4.17
375	1.32	53.78
376	0.06	2.02
377	1.08	9.37
378	0.38	18.64
379	0.12	2.96
380	0.84	41.54
381	3.37	16.99
382	0.35	22.41
383	2.58	20.27
384	0.24	23.30
385	1.69	20.76
386	0.14	14.12
387	0.08	2.76
388	0.13	10.17
389	0.09	3.75
390	0.13	1.80
391	0.05	5.50
392	0.13	6.90
393	0.13	3.84
394	0.19	4.62
395	0.12	3.20
396	0.11	6.78
397	0.98	42.55
398	0.08	3.29
399	0.15	3.88
400	0.11	15.39
401	0.04	3.37
402	0.07	12.41
403	0.15	7.47
404	0.10	14.35
405	0.11	3.42
406	0.13	6.01
407	0.26	8.55
408	0.05	3.44
409	0.20	26.77
410	0.13	4.19
411	0.04	19.03
412	0.05	48.29
413	0.10	25.63
414	0.03	26.18
415	0.18	11.94
416	0.07	2.58
417	0.18	27.01
418	0.18	5.97
419	0.32	12.70
420	0.12	6.55
421	0.13	2.33
422	0.07	11.49
423	0.18	15.42
424	0.04	1.13
425	0.57	51.95
426	1.62	32.44
427	0.16	2.64
428	0.07	2.94
429	0.19	41.64
430	0.11	19.84
431	0.17	27.49
432	0.07	4.73
433	0.21	7.43
434	0.06	2.11
435	0.08	7.52
436	0.08	6.04
437	0.27	9.67
438	0.04	2.70
439	1.47	25.62
440	0.21	3.53
441	0.17	10.73
442	0.12	3.78
443	0.22	6.45
444	0.13	6.31
445	0.56	33.52
446	0.73	19.28
447	0.08	2.31
448	0.13	4.50
449	0.10	2.93
450	0.13	4.97
451	0.16	7.79
452	0.18	13.03
453	0.35	43.95
454	0.14	16.15
455	0.84	32.43
456	0.23	17.80
457	0.250	21.55
458	0.13	15.17
459	0.18	7.06
460	0.24	12.18
461	0.13	9.34
462	0.18	13.26
463	0.42	43.64
464	0.14	3.07
465	0.14	7.25
466	1.19	14.54
467	1.07	14.51
468	0.13	14.51
469	0.24	26.09
470	0.98	37.45
471	0.50	15.00
472	0.11	5.63

Biological Example 2

MDR1-MDCK Bidirectional Permeability Assay

The blood-brain barrier (BBB) is composed of brain capillary endothelial cells, which are characterized by highly developed tight junctions. The BBB plays a key role in the brain penetration of drugs and is an obstacle to the discovery of drugs where the drug target is in the central nervous system (CNS). P-Glycoproteins (P-gp, MDR1) are highly expressed at the BBB and serve to actively efflux drugs out of the brain and therefore may limit brain penetration of drugs to the desired target. A bidirectional permeability assay using Madin Darby canine kidney cells expressing multi-drug resistance gene 1 (MDCK-MDR1) is routinely used to evaluate discovery compounds' BBB permeability and drug efflux toward the advancement of discovery compounds with brain penetration.

MDCK-MDR1 Cells (NIH cell line) were obtained from the National Institutes of Health. MDCK-MDR1 cells were diluted to 1.56 million cells/mL (NIH) with culture medium and 50 μL of cell suspension were dispensed into the filter wells of a 96-well HTS Transwell plate. Cells were cultivated for 4-8 days in a cell culture incubator at 37° C., 5% CO₂, 95% relative humidity. Cell culture medium was replaced every other day, beginning no later than 24 hours after the initial plating. The permeability assay used buffer was Hanks' balanced salt solution containing 10 mM HEPES at a pH of 7.4. The dosing solution concentration was 1 μM for the test article in the assay buffer. Cell monolayers were dosed on the apical side (A-to-B) or basolateral side (B-to-A) and incubated at 37° C. under an atmosphere of 5% CO₂ in a humidified incubator. Samples were taken from the donor and receiver chambers at 120 minutes. Each determination was performed in duplicate. After the 120 min transport period, the flux of lucifer yellow was also measured for each monolayer to ensure no damage was inflicted to the cell monolayers during the transport period. All samples were assayed by LC-MS/MS (Waters XSelect HSS T3 C18, 2.5 m, 2.1×50 mm) using electrospray ionization with 0.1% formic acid in water (mobile phase A) and 0.1% formic acid in acetonitrile (mobile phase B) as mobile phases. The apparent permeability coefficient (Papp), in units of cm per second, was calculated for MDCK-MDR1 Cells (NIH cell line) drug transport assays using the following equation:

$\mathrm{Papp}=\left(V_A\times {\left[\mathrm{drug}\right]}_{\mathrm{acceptor}}\right)/\left(\mathrm{Area}\times \mathrm{Time}\times {\left[\mathrm{drug}\right]}_{\mathrm{initial},\mathrm{donor}}\right)$

Where V_A is the volume (in mL) in the acceptor well, Area is the surface area of the membrane (0.143 cm² for Transwell-96 Well Permeable Supports), and time is the total transport time in seconds.

$\mathrm{Efflux}\mathrm{ratio}\left(\mathrm{ER}\right)\mathrm{is}\mathrm{defined}\mathrm{as}{P}_{\mathrm{app}}\left(B-\mathrm{to}-A\right)/P_{\mathrm{app}}\left(A-\mathrm{to}-B\right).$

The leakage of Lucifer Yellow (LY), in unit of percentage (%), can be calculated using the following equation:

$\%\mathrm{LY}\mathrm{leakage}=100\times {\left[\mathrm{LY}\right]}_{\mathrm{acceptor}}/\left({\left[\mathrm{LY}\right]}_{\mathrm{donor}}+{\left[\mathrm{LY}\right]}_{\mathrm{acceptor}}\right)$

LY leakage of <1% is acceptable to indicate the well-qualified MDCK-MDR1(NIH) monolayer.

The following comparator compounds were made using the procedures described above.

Results are shown in Table B.

TABLE B
Compound No.	PappAB	Efflux ratio
43	5.4	0.92
Comparator 1	1.85	14.7
40	3.4	1.9
Comparator 2	0.77	21.4
232	9.8	1.5
Comparator 3	2.1	24.5
80	13.3	2.8
Comparator 4	1.0	19.7
31	6.6	7.2
Comparator 5	0.7	27.2
234	9.80	1.52
8	9.77	5.41
452	9.47	4.01
7	9.16	3.09
464	9.11	2.19
70	9.10	1.04
35	8.31	2.90
376	8.06	4.11
26	7.93	3.82
27	7.68	1.99
31	6.63	7.25
30	6.31	4.07
Comparator 6	0.5	64
54	5.76	5.79
23	6.30	2.00
452	5.82	4.44
32	5.57	3.32
43	5.39	0.92
5	5.32	7.02
414	4.58	3.96
18	4.52	7.34
65	3.89	6.09
469	3.72	4.04
449	3.53	5.74
40	3.38	1.93
424	3.37	7.46
395	2.81	5.02
21	2.79	3.74
51	13.82	1.23
132	13.54	2.26
59	13.26	1.11
4	11.11	3.27

Biological Example 3

Brain Exposure Assay in Mice

This protocol was used to determine the brain-to-plasma ratio in vivo in mice post oral administration of test compounds. Mice (C57BL/6JNIFDC, male, non-fasted, 18-30 g body weight, 3 mice for each timepoint) were dosed orally at 100 mg/kg (10 mg test compound/mL formulation, 10 mL dosing volume/kg) with plasma and brain tissues obtained at 2- and 6-hours post-administration. The oral dosing formulation composition used was 10% N,N-dimethylacetamide:20% propylene glycol:70% of 40% aqueous 2-hydroxypropyl-β-cyclodextrin.

For the isolation of mouse plasma from dosed animals, approximately 0.3 mL blood was collected by orbital sinus bleed and centrifuged (4000 g, 5 minutes, 4° C.). The plasma samples were stored frozen at −75±15° C. until further processing.

For the isolation of brain tissue from dosed animals, whole brain tissues were collected from euthanized and fully exsanguinated mice. The tissues were quickly rinsed with distilled water, dried with absorbent paper, followed by rapid freezing on dry ice and then storage at −75±15° C. until further processing. Brain tissue samples obtained from frozen whole brain were weighed and the samples homogenized using three equivalents of distilled water (3 mL per gram of brain tissue).

Standard and quality control samples were prepared by adding 3 μL of the test compound dimethyl sulfoxide (DMSO) stock solutions to blank plasma (30 μL) and blank brain homogenate aliquots (30 μL). Standard curves for brain and plasma were generated over a 1 to 1,000 ng/g test compound concentration range. For the extraction of test compound from plasma and brain tissue homogenate samples, a solution of acetonitrile containing internal standard (400 L) was added to 30 μL of samples with added 3 μL of DMSO. The samples then were vortex-mixed followed by centrifugation at 4000 rpm (4° C., 15 minutes). The resultant supernatants were diluted 5-fold with distilled water. Finally, 10 μL of the diluted supernatant was injected onto an LC-MS/MS instrument for quantitative analysis of test compound.

The brain tissue concentration was calculated by multiplying the concentration of drug detected in the homogenized brain tissue sample by a dilution factor of 4.

The brain-to-plasma ratio was calculated by the relationship: Brain-to-plasma ratio=C_brain/C_plasma; where C_b is the concentration in brain tissue and C_p is the concentration in plasma at the corresponding timepoint.

Kp is the total brain-plasma concentration ratio; K_p=C_brain/C_plasma.

Kp, uu is the unbound brain-to-plasma partition coefficient (K_p,uu,brain). It is a measure of the extent of the distribution equilibrium of a compound between the unbound (free) fractions in brain and in blood plasma; K_{p, uu brain}=C_{u, brain}/C_{u, plasma}.

A compound is estimated as “brain penetrant” if its brain-to-plasma concentration ratio is >0.04, as cerebral blood volume is estimated at 4% of total brain volume (Shaffer CL (2010), Defining Neuropharmacokinetic Parameters in CNS Drug Discovery to Determine Cross-Species Pharmacologic Exposure-Response Relationships, Annual Reports in Medicinal Chemistry, 45:55-70, https://doi.org/10.1016/S0065-7743(10)45004-6).

		Brain
		tissue	Cplasma, total	Cbrain, total	Cplasma, free	Cbrain, free
	PPB	binding	(μM),	(μM),	(μM),	(μM),	Kp	Kp, uu
Co.	(mouse)	(mouse)	100 mg/kg,	100 mg/kg,	100 mg/kg,	100 mg/kg,	2 hr,	2 hr,
No.	% unbound	% unbound	2 hr, 6 hr	2 hr, 6 hr	2 hr, 6 hr	2 hr, 6 hr	6 hr	6 hr
54	4.5	2.2	43.0,	27.3,	1.94,	0.60,	0.63,	0.32,
			8.3	4.6	0.77	0.01	0.55	0.27
80	20	27	25.7,	14.1,	5.14,	3.8,	0.55,	0.74,
			5.3	3.0	1.06	0.81	0.57	0.77
30	4.9	8.5	45.0,	18.3,	2.20,	1.56,	0.41,	0.71,
			11.8	4.8	0.58	0.41	0.41	0.71
18	7.6	14.8	75.3,	9.4,	5.72,	1.41,	0.12,	0.25,
			25.4	3.4	1.93	0.51	0.13	0.25
27	3.7	5.3	42.1,	12.0,	1.55,	0.64,	0.29,	0.41,
			5.9	1.5	0.22	0.07	0.25	0.32
7	5.7	20.4	89.5,	20.8,	5.10,	4.24,	0.23,	0.83,
			20.2	4.0	1.15	0.82	0.20	0.71
449	2.2	3.3	59.4,	25.0,	1.30,	0.83,	0.42,	0.64,
			18	8.4	0.39	0.28	0.47	0.72
376	2.4	13.2	104,	16.5,	2.48,	2.2,	0.16,	0.89,
			45.5	7.5	1.09	1.0	0.16	0.92
400	4.3	5.4	13.5,	5.8,	0.58,	0.31,	0.43,	0.53,
			3.1	1.4	0.14	0.08	0.43	0.57
399	1.0	1.2	44,	19.5,	0.44,	0.23,	0.44,	0.52,
			26.8	11.5	0.27	0.14	0.43	0.52
424	16.5	9.2	11.7,	2.6,	1.94,	0.24,	0.22,	0.12,
			1.9	0.5	0.31	0.05	0.26	0.16
51	6.5	7.8	48.8,	18.5,	3.17,	1.44,	0.38,	0.45,
			11.0	4.5	0.72	0.35	0.41	0.49
80	19.5	26.9	25.7,	14.1,	5.01,	3.8,	0.55,	0.74,
			5.3	3.0	1.03	0.81	0.57	0.77
Compar-	52.3	51.8	40.1,	3.2,	20.6,	1.66,	0.08,	0.08,
ator 4			7.3	0.7	3.82	0.40	0.10	0.10

All publications, patent applications, patents, and other references mentioned herein are expressly incorporated by reference in their entireties, to the same extent as if each were incorporated by reference individually.

It is to be understood that, while the disclosure provided herein has been described in conjunction with the above embodiments, the foregoing description and examples are intended to illustrate and not limit the scope of the disclosure. Other aspects, advantages, and modifications within the scope of the disclosure will be apparent to those skilled in the art to which the disclosure pertains.

Claims

1. A compound of Formula (I)

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is

3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein RD is halogen or —O(C1-C6 alkyl) optionally substituted with 1 to 3 independently selected halogens.

4. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein RD is halogen.

5. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein RD is fluorine.

6. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein RD is chlorine.

7. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is 5- to 6-membered heteroaryl optionally substituted with 1 to 4 RA.

8. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is 5-membered heteroaryl optionally substituted with 1 to 4 RA.

9. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is oxazolyl, pyrazolyl, thiazolyl, isothiazolyl, or isoxazolyl, each of which is optionally substituted with 1 to 3 RA.

10. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is oxazolyl optionally substituted with 1 to 2 RA.

11. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is oxazol-5-yl optionally substituted with 1 to 2 RA.

12. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is thiazolyl optionally substituted with 1 to 2 RA.

13. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is 6-membered heteroaryl optionally substituted with 1 to 4 RA.

14. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is pyridinyl, pyridazinyl, or pyrimidinyl, each of which is optionally substituted with 1 to 4 RA.

15. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is pyridinyl optionally substituted with 1 to 4 RA.

16. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is pyridin-4-yl optionally substituted with 1 to 4 RA.

17. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each RA is independently selected from the group consisting of halogen and C1-C6 alkyl.

18. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring B is 4- to 8-membered heterocycloalkyl, 3- to 8-membered cycloalkyl, or 5- to 6-membered heteroaryl.

19. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring B is pyridinyl, piperazinyl, morpholinyl, piperidinyl, pyrrolidinyl, oxazolyl, or pyrazolyl.

20. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring B is pyridinyl, piperazinyl, morpholinyl, piperidinyl, or pyrrolidinyl.

21. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring B is

22. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each RB is independently selected from the group consisting of: halogen;oxo;—O(C1-C6 alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens;C1-C6 alkyl optionally substituted with 1 to 5 substituents independently selected from halogen, —OH, 4- to 8-membered heterocycloalkyl, and —O(C1-C6 alkyl);—S(O)2(C1-C6 alkyl);—S(O)2(4- to 8-membered heterocycloalkyl);—S(O)2(3- to 8-membered cycloalkyl);—S(O)2NRB1RB2;—C(O)NRB1RB2;—C(O)(C1-C6 alkyl);—C(O)O(C1-C6 alkyl);—C(O)(3- to 8-membered cycloalkyl) optionally substituted with 1 to 3 independently selected halogens;—C(O)(4- to 8-membered heterocycloalkyl) optionally substituted with 1 to 3 independently selected halogens;4- to 8-membered heterocycloalkyl; and5- to 6-membered heteroaryl.

23. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each RB is independently selected from the group consisting of oxo, —C(O)(C1-C6 alkyl), —C(O)NRB1RB2, —S(O)2(C1-C6 alkyl), —S(O)2NRB1RB2, unsubstituted C1-C6 alkyl, 4- to 8-membered heterocycloalkyl, and 5- to 6-membered heteroaryl.

24. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each RB is independently selected from the group consisting of —O(C1-C4 alkyl) optionally substituted with phenyl or 1 to 3 independently selected halogens; and C1-C4 alkyl optionally substituted with 1 to 5 substituents independently selected from halogen, —OH, 4- to 8-membered heterocycloalkyl, and —O(C1-C4 alkyl);

25. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each RB is independently selected from the group consisting of oxo, —C(O)(C1-C3 alkyl), —C(O)N(Me)2, —C(O)(4- to 8-membered heterocycloalkyl) optionally substituted with 1 to 3 independently selected halogens, —C(O)(3- to 8-membered cycloalkyl) optionally substituted with 1 to 3 independently selected halogens; —S(O)2(C1-C3 alkyl), —S(O)2N(Me)2, —C(O)O(C1-C4 alkyl), —S(O)2(4- to 8-membered heterocycloalkyl), —S(O)2(3- to 4-membered cycloalkyl), methyl, oxetanyl, and pyridinyl.

26. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein L is a bond, C1-C6 alk7ylene, #—C(O)—N(RL)—(C1-C6 alkylene)-$, #—C(O)—(C1-C6 alkylene)-$, or #—(C1-C6 alkylene)-C(O)—N(RL)—(C1-C6 alkylene)-$, wherein #represents the attachment point to ring B, and $ represents the attachment point to the remainder of the molecule; wherein each C1-C6 alkylene of L is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C1-C6 alkyl; andwherein each RL is independently hydrogen or C1-C6 alkyl.

27. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each C1-C6 alkylene of L is substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C1-C6 alkyl.

28. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each C1-C6 alkylene of L is substituted with 1 to 3 substituents independently selected from the group consisting of halogen and C1-C6 alkyl.

29. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each C1-C6 alkylene of L is substituted with 1 to 3 substituents independently selected from the group consisting of fluoro and methyl.

30. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each C1-C6 alkylene of L is unsubstituted.

31. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein L is a bond, C1-C3 alkylene, or #—C(O)—N(RL)—(C1-C3 alkylene)-$, wherein #represents the attachment point to ring B, and $ represents the attachment point to the remainder of the molecule; wherein each C1-C6 alkylene of L is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, and C1-C6 alkyl; andwherein each RL is independently hydrogen or C1-C6 alkyl.

32. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein L is a bond, —CH2—, —CH2CH2—, or

33. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein m is 1.

34. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein m is 0.

35. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, or 2.

36. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein RC is fluoro.

37. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein p is 0.

38. A compound selected from the group consisting of compounds 1-356 of Table 1, or a pharmaceutically acceptable salt thereof.

39. A compound selected from the group consisting of the compounds of Table 1, or a pharmaceutically acceptable salt thereof.

40. A compound selected from the group consisting of:

41. A pharmaceutical composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable-excipient.

42. A method of treating a disease or condition mediated by NAMPT activity in a subject in need thereof, comprising administering to the subject a compound of claim 1, or a pharmaceutically acceptable salt thereof.

43. The method of claim 42, wherein the disease or condition is selected from the group consisting of cancer, a hyperproliferative disease or condition, an inflammatory disease or condition, a metabolic disorder, a cardiac disease or condition, chemotherapy induced tissue damage, a renal disease, a metabolic disease, a neurological disease or injury, a neurodegenerative disorder or disease, diseases caused by impaired stem cell function, diseases caused by DNA damage, primary mitochondrial disorders, and a muscle disease or muscle wasting disorder.

44. The method of claim 42, wherein the disease or condition is selected from the group consisting of obesity, atherosclerosis, insulin resistance, type 2 diabetes, cardiovascular disease, Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, depression, Down syndrome, neonatal nerve injury, aging, axonal degeneration, carpal tunnel syndrome, Guillain-Barre syndrome, nerve damage, polio (poliomyelitis), and spinal cord injury.