Small Molecule IL-17A Modulators

Abstract

Disclosed herein are fused bi-cyclic compounds used as Small Molecule IL-17A Modulators. Disclosed herein is the use of these Small Molecule IL-17A Modulators for the use of decreasing IL-17 activity by inhibition, and the use of such compounds for the use in the treatment of autoimmune diseases or inflammatory diseases.

Description

FIELD OF THE INVENTION

Disclosed herein are fused bi-cyclic compounds used as Small Molecule IL-17A Modulators. Disclosed herein is the use of these Small Molecule IL-17A Modulators for the use of decreasing IL-17 activity by inhibition, and the use of such compounds for the use in the treatment of autoimmune diseases or inflammatory diseases.

BACKGROUND OF THE INVENTION

Interleukin-17(IL-17) family is a group of pro-inflammatory cytokines, which are involved in the immune response of tissues and played a critical role in chronic inflammation. The secretion of IL-17 can stimulate the production of other proinflammatory cytokines (IL-1, IL-6, G-CSF, GM-CSF, and TNF) and chemokines (CXCL1, CXCL2, CXCL5, CCL2, CCL7, CCL20, and IL-8), matrix metalloproteinases (MMP1, MMP3, MMP9, and MMP13), and anti-microbial peptides (β-defensins, S-100 proteins) (Frontiers in Immunology (2020) 11: 947). IL-17 family is composed of 7 members including IL17A to IL17F and vIL-17A. IL-17A, as the founder member with most widely studied, is associated with host defense against various microbial pathogens and tissue inflammation (Gene (2017) 614: 8-14). IL-17A consists of 155 amino acids and the molecular mass of the homodimer is 30-35 kDa (European Respiratory Journal (2005): 159-172). IL-17F, the closest relative of IL-17A, shares around 50% amino acid sequence homology with IL-17A over its 163 amino acids and is often co-expression with IL-17A (Immunity (2004): 467-476). Both IL-17A and IL-17F are secreted from T helper cells (Th17) and expressed as either homodimers or IL-17A/F heterodimer (European Respiratory Journal (2005): 159-172). The family of IL-17 receptors composes of five members: IL-17RA, IL-17RB, IL-17RC, IL-17RD, and IL-17RE. All of these five receptors share a common cytoplasmic motif named as SEFIR domain (Frontiers in Immunology 11 (2020): 947). The signal pathway of IL-17A and IL-17F through the same receptor complex IL-17R consists of two subunits: IL-17RA and IL-17RG (Gene (2017) 614: 8-14). The correspondent receptors activate the downstream pathway of these signaling including NFκB, MAPKs and C/EBPs to induce the expression of anti-microbial peptides, cytokines and chemokines (Frontiers in Immunology (2020): 947). IL-17A promotes tissue inflammation and bone remodeling. It can act on various cell types: keratinocytes, endothelial cells, fibroblasts, osteoclasts, chondrocytes, and osteoblasts (Archives of oral biology (2014): 897-905).

The abnormal autoimmune response of IL-17A increasing secretion is observed in many autoimmune diseases including psoriasis, spondylarthritis, rheumatoid arthritis, and multiple sclerosis (Gene (2017) 614: 8-14). One potential treatment of these diseases is to develop IL-17A inhibitors. Currently, several monoclonal antibodies targeting IL-17A are approved by the FDA for the treatment of moderate-to-severe plaque psoriasis (Expert Opin. Biol. Ther. (2019), 19, 45-54): secukinumab (Cosentyx, Novartis), ixekizumab (Taltz, Eli Lilly), and brodalumab (Kyntheum, LEO Pharma/AstraZeneca). Bimekizumab (UCB) is a bispecific anti-IL-17A/IL-17F humanized monoclonal antibody that was just approved in 2021 by EC. However, since monoclonal antibodies have a number of disadvantages, such as high cost-of-goods, non-oral applications, poor tissue penetration, and often long half-lives (Chem. Biol. (2014) 21, 1102-1114), the search for small molecules that would exhibit the same biological outcome is still ongoing. Some disclosures are known to describe the small molecule with IL-17A inhibition activity (WO2014066726, WO2018229079, WO2019138017, WO2019223718, WO2020182666, WO2020011731, WO2020127685, WO2020163554, WO2021055376, WO2021098844, 2020163554 WO2020146194, WO2021204801, WO2021170627, WO2021098844, WO2021222404, WO2021220183). Several small molecule inhibitors targeting protein/protein interaction of IL-17A and IL-17RA have been advanced into clinical trials now. Oral administration and flexible treatment regimen are supposed to be main aspects in favor of patient's convenience. The possibility of fast withdraw of small molecule drug may present approved safety when target-related adverse events occur. Therefore, there is a continuous need to develop small molecule IL-17A modulator with diverse structure, particularly that can be orally administrated.

SUMMARY OF THE INVENTION

In one embodiment, disclosed herein is fused bi-cyclic compound of Formula (I). The embodiment comprises the following aspects:

Aspect 1. A compound of Formula (I):

• • or a N-oxide thereof, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a deuterated analog thereof, wherein:
  • Cy1 is a 5-6 membered aromatic ring, said ring comprising 0-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R³;
  • n3 is independently 0, 1, 2 or 3;
  • Cy2 is a 4-8 membered saturated or partially or completely unsaturated ring, said ring comprising 0-3 heteroatoms independently selected from nitrogen, oxygen or optionally oxidized sulfur; said ring is substituted with at least one substituent R¹ and/or R²;
  • n1 is 0 or 1;
  • n2 is 0, 1 or 2;
  • n1 and n2 are not 0 at the same time;
  • Cy1 and Cy2 are fused with each other;
  • Cy3 is a 3-12 membered saturated or partially or completely unsaturated ring, said ring comprising 0-3 heteroatoms independently selected from nitrogen, oxygen or optionally oxidized sulfur; said ring is optionally substituted with at least one substituent R⁶;
  • n6 is independently 0, 1, 2, 3, 4 or 5, provided that the valency theory is met;
  • X¹ is a single bond or —CR⁹R¹⁰—;
  • R¹ is independently selected from H or

• • wherein X² is N or C(R¹⁵);
    • X³ is —C(O)—, —S(O)— or —S(O)₂—;
    • n11 and n12 are each independently 1, 2 or 3;
    • n14 is 0 or 1;
  • R¹⁵ is selected from hydrogen, halogen, —C_1-8alkyl, —C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, —CN, —OR^15a, —NR^15aR^15b, or —NR^15aCOR^15b; each of —C_1-8alkyl, C₃-C₈cycloalkyl and 3- to 8-membered heterocyclyl is optionally substituted with at least one substituent R^15c,
  • R^15a and R^15b are each independently selected from hydrogen, —C_1-8alkyl, —C_1-8haloalkyl, —C_2-8alkenyl, —C_2-8alkynyl, C_1-8alkoxy-C_1-8alkyl-, C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl, each of —C_1-8alkyl, —C_1-8haloalkyl, —C_2-8alkenyl, —C_2-8alkynyl, C_1-8alkoxy-C_1-8alkyl-, C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl and 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^15d;
  • R^15c and R^15d, at each occurrence, are each independently halogen, —OH, —CN, oxo, —C_1-8alkyl, —C_1-8 haloalkyl, —C_1-8alkoxy, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, —C₃-C₈halocycloalkyl, 3- to 8-membered heterocyclyl, —C₆-C₁₂aryl, or 5- to 12-membered heteroaryl;
  • R^11a, R^11b, R^12a and R^12b are each independently selected from hydrogen, halogen, —C_1-8alkyl, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl, 5- to 12-membered heteroaryl, —CN, —OR^11c, —COR^11c, —CO₂R^11c, —CONR^11cR^11d, —NR^11cR^11d or —NR^11cCOR^11d; each of —C_1-8alkyl, C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^11e, or
  • (R^11a and R^11b), (R^12a and R^12b), (R^11a and R^12a), (R^11a and R^12b), (R^11b and R^12a) or (R^11b and R^12b) together with the atom(s) to which they are attached, form a 3- to 8-membered unsaturated or saturated ring, said ring comprising 0-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R^11f;
  • R^11e and R^11f at each occurrence, are each independently hydrogen, halogen, —C_1-8alkyl, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl, 5- to 12-membered heteroaryl, oxo (═O), —OR^11g, thioxo (═S), —SR^11g, —CN, —SO₂R^11g, —SO₂NR^11gR^11h, —COR^11g, —CO₂R^11h, —CONR^11gR^11h, —NR^11gR^11h, —NR^11gCOR^11h, —NR^11gCO₂R^11h or —NR¹SO₂R^11h; each of —C_1-8alkyl, —C_1-8alkoxy, C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R¹¹ⁱ;
  • R^11c, R^11d, R^11g and R^11h are each independently selected from hydrogen, —C_1-8alkyl, —C_1-8haloalkyl, —C_2-8alkenyl, —C_2-8alkynyl, C_1-8alkoxy-C_1-8alkyl-, C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl; each of —C_1-8alkyl, —C_1-8haloalkyl, —C_2-8alkenyl, —C_2-8alkynyl, C_1-8alkoxy-C_1-8alkyl-, C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl and 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^11j;
  • at each occurrence, R¹¹ⁱ and R^11j are each independently halogen, —OH, —CN, oxo, —C_1-8alkyl, —C_1-8 haloalkyl, —C_1-8alkoxy, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, —C₃-C₈halocycloalkyl, 3- to 8-membered heterocyclyl, —C₆-C₁₂aryl, or 5- to 12-membered heteroaryl; each of —C_1-8alkyl, —C_1-8alkoxy, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, —C₆-C₁₂aryl, or 5- to 12-membered heteroaryl is optionally substituted with at least one substituent halogen, —OH, —CN, oxo, —C_1-8alkyl, —C_1-8haloalkyl, —C_1-8alkoxy, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, —C₃-C₈halocycloalkyl, 3- to 8-membered heterocyclyl, —C₆-C₁₂aryl, or 5- to 12-membered heteroaryl;
  • R¹³, R^14a and R^14b are each independently selected from hydrogen, —C_1-8alkyl, —C₃-C₈cycloalkyl or 3- to 8-membered heterocyclyl; each of —C_1-8alkyl, —C₃-C₈cycloalkyl and 3- to 8-membered heterocyclyl is optionally substituted with at least one substituent R^13a;
  • R^13a, at each occurrence, is independently halogen, —OH, —CN, oxo, —C_1-8alkyl, —C_1-8haloalkyl, —C_1-8alkoxy, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, —C₃-C₈halocycloalkyl, 3- to 8-membered heterocyclyl, —C₆-C₁₂aryl, or 5- to 12-membered heteroaryl;
  • R² is independently selected from H, —C_1-8alkyl, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, C₆-C₁₂aryl, 5- to 12-membered heteroaryl, —CN, —COR^2a, —CO₂R^2a, —CONR^2aR^2b, —NR^2aR^2b, or —NR^2aCOR^2b, each of —C_1-8alkyl, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, C₆-C₁₂aryl and 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^2c; or
  • when geminal or adjacent, two R² together with the carbon atom(s) to which they are attached, form a 3- to 8-membered unsaturated or saturated ring, said ring comprising 0-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R^2c;
  • R^2a and R^2b are each independently selected from hydrogen, —C_1-8alkyl, —C_2-8alkenyl, —C_2-8alkynyl, C₃-C₁₂cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl; each of —C_1-8alkyl, —C_2-8alkenyl, —C_2-8alkynyl, C₃-C₁₂cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl and 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^2d; or
  • R^2a and R^2b together with the nitrogen atom to which they are attached, form a 3- to 8-membered unsaturated or saturated ring, said ring comprising 0-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R^2d;
  • R^2c and R^2d, at each occurrence, are each independently hydrogen, halogen, —C_1-8alkyl, —C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl, 5- to 12-membered heteroaryl, oxo (═O), —OR², —SR^2e, —CN, —COR^2e, —CO₂R^2e, —CONR^2eR^2f, —NR^2eR^2f, —NR^2eCOR^2f or —NR^2eCO₂R^2f; each of —C_1-8alkyl, C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^2g;
  • R^2e and R^2fare each independently selected from hydrogen, —C_1-8alkyl, —C_1-8alkoxy, C_1-8alkoxy-C_1-8 alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, C₃-C₁₂cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl; each of —C_1-8alkyl, —C_1-8alkoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, C₃-C₁₂cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl and 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^2h;
  • R^2g and R^2h, at each occurrence, are each independently halogen, —OH, —C_1-8alkyl, —C_1-8haloalkyl, —C_1-8alkoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, —C₃-C₈halocycloalkyl, 3- to 8-membered heterocyclyl, —C₆-C₁₂aryl, or 5- to 12-membered heteroaryl;
  • when n1 and n2 are both 1, R¹ and R² are geminal or adjacent;
  • R³ is independently selected from hydrogen, halogen, —C_1-8alkyl, —C_1-8alkoxy, —C₃-C₈cycloalkyl, or —CN, wherein each of —C_1-8alkyl, —C_1-8alkoxy and —C₃-C₈cycloalkyl is optionally substituted with at least one substituent selected from halogen, —OH, —C_1-8alkyl, —C_1-8alkoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, —C₆-C₁₂aryl, or 5- to 12-membered heteroaryl;
  • R⁴ is oxo (═O) or thioxo (═S); or
  • R³ and R⁴ together with the atoms to which they are attached, form a 5- to 6-membered aromatic ring, said ring comprising 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R^3a;
  • R^3a is independently selected from hydrogen, halogen, —C_1-8alkyl, —C_1-8alkoxy, —C₃-C₈cycloalkyl, or —CN, wherein each of —C_1-8alkyl, —C_1-8alkoxy and —C₃-C₈cycloalkyl is optionally substituted with at least one substituent selected from halogen, —OH, —C_1-8alkyl, —C_1-8alkoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, —C₆-C₁₂aryl, or 5- to 12-membered heteroaryl;
  • R⁵ is C₆-C₁₂aryl, 5- to 12-membered heteroaryl, —COR^5a, —CO₂R^5a, —CONR^5aR^5b, wherein each of C₆-C₁₂aryl and 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^5c;
  • R^5a and R^5b are each independently selected from —C_1-8alkyl, —C_2-8alkenyl, —C_2-8alkynyl, C₃-C₁₂cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl; each of —C_1-8alkyl, —C_2-8alkenyl, —C_2-8alkynyl, C₃-C₁₂cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl and 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^5d; or
  • R^5a and R^5b together with the atom to which they are attached, form a 3- to 8-membered unsaturated or saturated ring, said ring comprising 0-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R^5d;
  • R^5c and R^5d, at each occurrence, are each independently selected from hydrogen, halogen, —C_1-8alkyl, —C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl, 5- to 12-membered heteroaryl, oxo (═O), —OR^5e, —SR^5e, —CN, —COR^5e, —CO₂R^5e, —CONR^5eR^5f, —NR^5eR^5f, —NR^5eCOR^5f or —NR^5eCO₂R^5f; each of —C_1-8alkyl, C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^5g;
  • R^5e and R^5fare each independently selected from hydrogen, —C_1-8alkyl, —C_1-8alkoxy, C_1-8alkoxy-C_1-8 alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, C₃-C₁₂cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl; each of —C_1-8alkyl, —C_1-8alkoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, C₃-C₁₂cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl and 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^5h;
  • R^5g and R^5h are each independently selected from halogen, —OH, —CN, —C_1-8alkyl, —C_1-8alkoxy, C_1-8 alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, —C₆-C₁₂aryl, or 5- to 12-membered heteroaryl;
  • R⁶ is H, halogen, —C_1-8alkyl, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, C₆-C₁₂aryl, 5- to 12-membered heteroaryl, —CN, —OR^6a, —NR^6aR^6b, —COR^6a, —CO₂R^6a, —CONR^6aR^6b, —COR^6a or —NR^6aCOR^6beach of —C_1-8alkyl, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, C₆-C₁₂aryl and 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^6d;
  • R^6a and R^6b are each independently selected from hydrogen, —C_1-8alkyl, —C_2-8alkenyl, —C_2-8alkynyl, C₃-C₁₂cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl; each of —C_1-8alkyl, —C_2-8alkenyl, —C_2-8alkynyl, C₃-C₁₂cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl and 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^6d;
  • R^6e, at each occurrence, is independently hydrogen, halogen, —C_1-8alkyl, —C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl, 5- to 12-membered heteroaryl, oxo (═O), —OR^6e, —SR^6e, —CN, —COR^6e, —CO₂R^6e, —CONR^6eR^6f, —NR^6eR^6f, —NR^6eCOR^6f or —NR^5eCO₂R^5f; each of —C_1-8alkyl, C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^6g;
  • R^6e and R^6f are each independently selected from hydrogen, —C_1-8alkyl, —C_1-8alkoxy, C_1-8alkoxy-C_1-8 alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, C₃-C₁₂cycloalkyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl;
  • R^6d and R^6g are each independently selected from halogen, —OH, —C_1-8alkyl, —C_1-8alkoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, —C₆-C₁₂aryl, or 5- to 12-membered heteroaryl;
  • R⁷ and R⁸ are each independently hydrogen;
  • R⁹ and R¹⁰ are each independently selected from H, halogen, —C_1-8alkyl, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl, each of —C_1-8alkyl, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, C₆-C₁₂aryl and 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^9a; and
  • R^9a, at each occurrence, is independently halogen, —OH, —C_1-8alkyl, —C_1-8alkoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈cycloalkyl, 3- to 8-membered heterocyclyl, —C₆-C₁₂aryl, or 5- to 12-membered heteroaryl.

Aspect 2. The compound of Aspect 1, wherein the compound is selected from Formula (IIa)-(IIp):

• • wherein, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, Cy3, n1, n2, n13, n6 and X¹ are defined as in Aspect 1.

Aspect 3. The compound of Aspect 1, wherein the compound is selected from Formula

• • wherein, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, Cy3, n1, n2, n3, n6 and X¹ are defined as in Aspect 1.

Aspect 4. The compound of Aspect 1, wherein the compound is selected from Formula (IIIa)-(IIIb):

• • wherein, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, Cy1, Cy2, Cy3, n1, n2, n3, n6, R⁹ and R¹⁰ are defined as in Aspect 1.

Aspect 5. The compound of Aspect 1, wherein the compound is selected from Formula (IVa)-(IVb):

• • wherein, X¹, R¹, R², R³, R⁵, R⁶, R⁷, R⁸, Cy1, Cy2, Cy3, n1, n2, n3, n6, R⁹ and R¹⁰ are defined as in Aspect 1.

Aspect 6. The compound of Aspect 1, wherein the compound is selected from Formula (Va)-(Vc):

• • wherein, X¹, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, Cy1, Cy2, Cy3, n3, n6, R⁹ and R¹⁰ are defined as in Aspect 1.

Aspect 7. The compound Aspect 1, wherein the compound is VIa,

• • preferably, the compound is selected from VIb and Vic

• • wherein, X¹, X², X³, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, Cy1, Cy2, Cy3, n2, n3, n6, R^11a, R^11b, R^12a, R^12b, R¹³, R^14a, R^14b, n11, n12 and n14 are defined as in Aspect 1.

Aspect 8. The compound Aspect 1, wherein the compound is VIIa or VIIb,

• • preferably, the compound is selected from VIIc, VIId, VIIe, VIIf, VIIg or VIIh,

• • wherein, X², R^2a, R³, R⁵, R⁶, R⁹, R¹⁰, Cy1, Cy2, Cy3, n2, n3, n6, R^11a, R^11b, R^12a, R^12b, R¹³, R^14a, R^14b, n11, n12 and n14 are defined as in Aspect 1.

Aspect 9. The compound of any one of the preceding Aspects, wherein Cy1 is a 5- or 6-membered aromatic ring, said ring comprising 0, 1 or 2 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with 0, 1, 2 or 3 substituents R³;

• • preferably, Cy1 is phenyl, pyridyl, thiophenyl, imidazolyl, furanyl or pyrazolyl; each of phenyl, pyridyl, thiophenyl, imidazolyl, furanyl or pyrazolyl is optionally substituted with 0, 1 or 2 substituents R³.

Aspect 10. The compound of any one of the preceding Aspects, wherein Cy2 a 4-, 5-, 6-, 7- or 8-membered saturated or partially or completely unsaturated ring, said ring comprising 0, 1, 2 or 3 heteroatoms independently selected from nitrogen or oxygen; said ring is substituted with at least one substituent R¹ and/or R²;

• • preferably, Cy2 a 5-, 6- or 7-membered saturated or partially or completely unsaturated ring, said ring comprising 0, 1 or 2 heteroatoms independently selected from nitrogen or oxygen; said ring is substituted with at least one substituent R¹ and/or R².

Aspect 11. The compound of any one of the preceding Aspects, wherein

moiety is selected from:

Aspect 12. The compound of any one of the preceding Aspects, wherein Cy3 is a 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11- or 12-membered saturated or partially or completely unsaturated ring, said ring comprising 0, 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen or optionally oxidized sulfur; said ring is optionally substituted with 0, 1, 2, 3, 4 or 5 substituent R⁶;

• • preferably, Cy3 is a 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11- or 12-membered saturated or partially or completely unsaturated ring, said ring is mono-cycle, bi-cycle or tri-cycle comprising 0, 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen or optionally oxidized sulfur; said ring is optionally substituted with 0, 1, 2, 3, 4 or 5 substituent R⁶;
  • more preferably,

• •  moiety is

• • even more preferably,

• •  moiety is

Aspect 13. The compound of any one of the preceding Aspects, wherein R¹ is independently selected from H,

• • wherein R^11a, R^11b, R^12a, R^12b, R¹³, n11 and n12 are defined as in Aspect 1.

Aspect 14. The compound of any one of the preceding Aspects, wherein R¹⁵ is selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, —CN, —OR^15a, —NR^15aR^15b, or —NR^15aCOR^15b; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and 3- to 8-membered heterocyclyl is optionally substituted with at least one substituent R^15C;

• • R^15a and R^15b are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_1-8haloalkyl, —C_2-8alkenyl, —C_2-8alkynyl, C_1-8alkoxy-C_1-8alkyl-, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl, each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, —C_2-8alkenyl, —C_2-8alkynyl, C_1-8 alkoxy-C_1-8alkyl-, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl and 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^15d;
  • R^15c and R^15d, at each occurrence, are each independently —F, —Cl, —Br, —I, —OH, —CN, oxo, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_1-8haloalkyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —C₃-C₈halocycloalkyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 12-membered heteroaryl.

Aspect 15. The compound of any one of the preceding Aspects, wherein R¹⁵ is selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, —CN, —OH, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy;

• • preferably, R¹⁵ is selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl;
  • more preferably, R¹⁵ is selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl;
  • even more preferably, R¹⁵ is selected from hydrogen.

Aspect 16. The compound of any one of the preceding Aspects, wherein R^11a, R^11b, R^12a and R^12b are each independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, —CN; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl and pyrazinyl is optionally substituted with at least one substituent R^11e;

• • R^11e, at each occurrence, is independently hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, oxo (═O), —OR^11g, thioxo (═S), —SR^11g, —CN, —SO₂R^11g, —SO₂NR^11gR^11h, —COR^11g, —CO₂R^11h, —CONR^11gR^11h, —NR^11gR^11h, —NR^11gCOR^11h, —NR^11gCO₂R^11h or —NR^11gSO₂R^11h; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl and pyrazinyl is optionally substituted with at least one substituent R¹;
  • R^11c, R^11d, R^11g and R^11h are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_1-8haloalkyl, —C_2-8alkenyl, —C_2-8alkynyl, C_1-8alkoxy-C_1-8alkyl-, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl or 5- to 12-membered heteroaryl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_1-8 haloalkyl, —C_2-8alkenyl, —C_2-8alkynyl, C_1-8alkoxy-C_1-8alkyl-, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl and 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^11j;
  • at each occurrence, R¹¹ⁱ and R^11j are each independently —F, —Cl, —Br, —I, —OH, —CN, oxo, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_1-8haloalkyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —C₃-C₈halocycloalkyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_1-8haloalkyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —C₃-C₈halocycloalkyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl is optionally substituted with at least one substituent —F, —Cl, —Br, —I, —OH, —CN, oxo, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_1-8haloalkyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —C₃-C₈halocycloalkyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 12-membered heteroaryl.

Aspect 17. The compound of any one of the preceding Aspects, wherein R^11a, R^11b, R^12a and R^12b are each independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, —CN; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl and pyrazinyl is optionally substituted with at least one substituent R^11e;

• • R^11e, at each occurrence, is independently hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, —OR^11g or —CN;
  • R^11g is independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl;
  • preferably, R^11a, R^11b, R^12a and R^12b are each independently selected from H, —CH₃, —CF₃, —CH₂CH₃, —CH₂CF₃, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, pyrrolidinyl, tetrahydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, benzyl, vinyl, propenyl, allyl, but-3-en-1-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl,

Aspect 18. The compound of any one of the preceding Aspects, wherein (R^11a and R^11b), (R^12aand R^12b), (R^11a and R^12a), (R^11a and R^12b), (R^11b and R^12a) or (R^11b and R^12b) together with the carbon atoms to which they are attached, form a 3-, 4-, 5-, 6- or 8-membered unsaturated or saturated ring, said ring comprising 0, 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R^11f;

• • R^11f at each occurrence, is independently hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl, 5- to 12-membered heteroaryl, oxo (═O), —OR^11g, thioxo (═S), —SR^11g, —CN, —SO₂R^11g, —SO₂NR^11gR^11h, —COR^11g, —CO₂R^11h, —CONR^11gR^11h, —NR^11gR^11h, —NR^11gCOR^11h, —NR^11gCO₂R^11h or —NR^11gSO₂R^11h.

R^11g and R^11h are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_2-8alkenyl, —C_2-8alkynyl, C_1-8alkoxy-C_1-8alkyl-, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, C₆-C₁₂aryl or 5- to 12-membered heteroaryl;

• • at each occurrence, R^11h is independently —F, —Cl, —Br, —I, —OH, —CN, oxo, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_1-8haloalkyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —C₃-C₈halocycloalkyl, 3- to 8-membered heterocyclyl, —C₆-C₁₂aryl, or 5- to 12-membered heteroaryl;
  • preferably, (R^11a and R^11b), (R^12a and R^12b), (R^11a and R^12a), (R^11a and R^12b), (R^11b and R^12a) or (R^11b and R^12b) together with the carbon atoms to which they are attached, form a 3-, 4-, 5-, 6- or 8-membered unsaturated or saturated ring;
  • more preferably, (R^11a and R^11b), (R^12a and R^12b), (R^11a and R^12a), (R^11a and R^12b), (R^11b and R^12a) or (R^11b and R^12b) together with the carbon atoms to which they are attached, form a 3-, 4-, 5-, 6- or 8-membered saturated ring;

Aspect 19. The compound of any one of the preceding Aspects, wherein R¹³, R^14a and R^14bare each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or 3- to 8-membered heterocyclyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or 3- to 8-membered heterocyclyl is optionally substituted with at least one substituent R^13a;

• • R^13a, at each occurrence, is independently halogen, —OH, —CN, oxo, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —C_1-8haloalkyl, —C_1-8alkoxy, —C_2-8alkenyl, —C_2-8alkynyl, —C₃-C₈halocycloalkyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 12-membered heteroaryl;
  • preferably, R¹³, R^14a and R^14b are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or 3- to 8-membered heterocyclyl;
  • more preferably, R¹³ is hydrogen, methyl, ethyl, propyl or butyl; R^14a and R^14b are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or 3- to 8-membered heterocyclyl; even more preferably, R¹³ is hydrogen; R^14a and R^14b are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl.

Aspect 20. The compound of any one of the preceding Aspects, wherein R¹ is selected from

Aspect 21. The compound of any one of the preceding Aspects, wherein R² is independently selected from H, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, —CN, —COR^2a, —CO₂R^2a, —CONR^2aR^2b, —NR^2aR^2b, —NR^2aCOR^2b, each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl and imidazopyridinyl is optionally substituted with at least one substituent R^2c;

• • R^2a and R^2b are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl is optionally substituted with at least one substituent R^2d; or
  • R^2a and R^2b together with the carbon atoms to which they are attached, form a 3-, 4-, 5-, 6-, 7- or 8-membered unsaturated or saturated ring, said ring comprising 0, 1, 2, 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R^2d;
  • R^2c and R^2d, at each occurrence, are each independently hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, oxo (═O), —OR^2e, —SR^2e, —CN, —COR^2e, —CO₂R^2e, —CONR^2eR^2f, —NR^2eR^2f, —NR^2eCOR^2f or —NR^2eCO₂R^2f; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl is optionally substituted with at least one substituent R^2g;
  • R^2e and R^2fare each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl or 5- to 12-membered heteroaryl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl or 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^2h
  • R^2g and R^2h, at each occurrence, are each independently —F, —Cl, —Br, —I, —OH, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_1-8haloalkyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —C₃-C₈halocycloalkyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 12-membered heteroaryl.

Aspect 22. The compound of any one of the preceding Aspects, wherein R² is independently selected from H, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, —CN, —COR^2a, —CO₂R^2a or —CONR^2aR^2b, each of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl is optionally substituted with at least one substituent R^2c;

• • R^2a and R^2b are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl is optionally substituted with at least one substituent R^2d; or
  • R^2a and R^2b together with the carbon atoms to which they are attached, form a 3-, 4-, 5- or 6-membered unsaturated or saturated ring, said ring comprising 0 or 1 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R^2d;
  • R^2c and R^2d, at each occurrence, are each independently hydrogen (H or D), —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, —OR^2e, —CN or —NR^2eR^2f; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl is optionally substituted with at least one substituent R^2g;
  • R^2e and R^2fare each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl is optionally substituted with at least one substituent R^2h
  • R^2g and R^2h, at each occurrence, are each independently —F, —Cl, —Br, —I, —OH, methyl, ethyl, propyl, butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;
  • preferably, R² is

Aspect 23. The compound of any one of the preceding Aspects, wherein R³ is independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or —CN, wherein each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl is optionally substituted with at least one substituent selected from —F, —Cl, —Br, —I, —OH, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, —C₆-C₁₂aryl, or 5- to 12-membered heteroaryl;

• • preferably, R³ is independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or —CN; more preferably, R³ is independently selected from hydrogen, —F, —Cl, —Br, —I.

Aspect 24. The compound of any one of the preceding Aspects, wherein R⁴ is oxo (═O).

Aspect 25. The compound of any one of the preceding Aspects, wherein R³ and R⁴ together with the carbon atoms to which they are attached, form a 5- to 6-membered aromatic ring, said ring comprising 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R^3a;

• • R^3a is independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —CN, wherein each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl is optionally substituted with at least one substituent selected from —F, —Cl, —Br, —I, —OH, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, —C₆-C₁₂aryl, or 5- to 12-membered heteroaryl.

Aspect 26. The compound of any one of the preceding Aspects, wherein R⁵ is phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, —COR^5a, —CO₂R^5a, or —CONR^5aR^5b, wherein each of phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl is optionally substituted with at least one substituent R^5c;

• • R^5a and R^5b are each independently selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, oxadiazolyl, triazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, oxadiazolyl, triazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl is optionally substituted with at least one substituent R^5d; or
  • R^5a and R^5b together with the nitrogen atom to which they are attached, form a 3-, 4-, 5-, 6-, 7- or 8-membered unsaturated or saturated ring, said ring comprising 0, 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R^5d;
  • R^5c and R^5d, at each occurrence, are independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, oxo (═O), —OR^5e, —SR^5e, —CN, —COR^5e, —CO₂R^5e, —CONR^5eR^5f, —NR^5eR^5f, —NR^5eCOR^5f or —NR^5eCO₂R^5f; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl is optionally substituted with at least one substituent R^5g;
  • R^5e and R^5fare each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C_1-8alkoxy-C_1-8alkyl-, —C_1-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl is optionally substituted with at least one substituent R^5h;
  • R^5g and R^5h are each independently selected from halogen, —OH, —CN, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C_1-8 alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl or 5- to 12-membered heteroaryl.

Aspect 27. The compound of any one of the preceding Aspects, wherein R⁵ is pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl, wherein each of pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, is optionally substituted with at least one substituent R^5c;

• • R^5c, at each occurrence, is independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl;
  • preferably, R is benzooxazolyl;
  • more preferably, R⁵ is

Aspect 28. The compound of any one of the preceding Aspects, wherein R⁵ is —COR^5a, CO₂R^5a, or —CONR^5aR^5b;

• • wherein R^5a and R^5b are each independently selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, oxadiazolyl, triazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl is optionally substituted with at least one substituent R^5d;
  • R^5d, at each occurrence, is independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, —OR^5e or —CN; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl is optionally substituted with at least one substituent R^5g;
  • R^5e is selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl is optionally substituted with at least one substituent R^5h;
  • R^5g and R^5h are each independently selected from halogen, —OH, —CN, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl or 5- to 12-membered heteroaryl;
  • preferably, R⁵ is

Aspect 29. The compound of any one of the preceding Aspects, wherein R⁶ is H, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, —CN, —OR^6a, —NR^6aR^6b, —COR^6a, —C₂R^6a, —CONR^6aR^6b, —COR^6a or —NR^6aCOR^6b, each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl is optionally substituted with at least one substituent R^6c;

• • R^6a and R^6b are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl or 5- to 12-membered heteroaryl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl or 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^6d;
  • R^6c, at each occurrence, is independently hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, 5- to 12-membered heteroaryl, oxo (═O), —OR^6e, —SR^6e, —CN, —COR^6e, —CO₂R^6e, —CONR^6eR^6f, —NR^6eR^6f, —NR^6eCOR^6f or —NR^6eCO₂R^6f; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^6g;
  • R^6e and R^6f are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl or 5- to 12-membered heteroaryl;
  • R^6d and R^6g are each independently selected from —F, —Cl, —Br, —I, —OH, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 12-membered heteroaryl;

Aspect 30. The compound of any one of the preceding Aspects, wherein R⁶ is H, —F, —Cl, —Br, —I, methyl, —CF₃, ethyl, —CH₂CF₃, —CF₂CH₃, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, —CN, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy,

• • preferably,

• •  moiety is

Aspect 31. The compound of any one of the preceding Aspects, wherein R⁹ and R¹⁰ are each independently selected from H, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl or 5- to 12-membered heteroaryl, each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl or 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R^9a;

• • R^9a, at each occurrence, is independently halogen, —OH, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C_1-8alkoxy-C_1-8alkyl-, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 12-membered heteroaryl;
  • preferably, R⁹ and R¹⁰ are each independently selected from H, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C_2-8alkenyl, —C_2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl or 5- to 12-membered heteroaryl;
  • more preferably, R⁹ and R¹⁰ are each independently selected from H, methyl, ethyl, propyl, butyl, pentyl, cyclopropyl, cyclobutyl, cyclopentyl;
  • more preferably, R⁹ and R¹⁰ are each independently selected from H, cyclopropyl.

Aspect 32. The compound of any one of the preceding Aspects, wherein the compound is selected from

Aspect 33. A pharmaceutical composition comprising a compound of any one of Aspects 1-32 or a pharmaceutically acceptable salt, stereoisomer, tautomer or prodrug thereof, together with a pharmaceutically acceptable excipient.

Aspect 34. A method of decreasing IL-17 activity by inhibition, which comprises administering to an individual the compound according to any one of Aspects 1-32, or a pharmaceutically acceptable salt thereof, including the compound of formula (I) or the specific compounds exemplified herein.

Aspect 35. The method of Aspect 34, wherein the disease is selected from cancer.

Aspect 36. Use of a compound of any one of Aspects 1-32 or a pharmaceutically acceptable salt, stereoisomer, tautomer or prodrug thereof in the preparation of a medicament for treating a disease that can be affected by IL-17.

Aspect 37. The use of Aspect 36, wherein the disease is autoimmune disease or inflammatory disease.

Aspect 38. The use of Aspect 37, wherein the disease is chronic inflammation, psoriasis, spondylarthritis, rheumatoid arthritis or multiple sclerosis.

DETAILED DESCRIPTION OF THE INVENTION

The following terms have the indicated meanings throughout the specification:

As used herein, including the appended Aspects, the singular forms of words such as “a”, “an” and “the”, include their corresponding plural references unless the context clearly dictates otherwise.

The term “or” is used to mean, and is used interchangeably with, the term “and/or” unless the context clearly dictates otherwise.

The term “alkyl” refers to a hydrocarbon group selected from linear and branched saturated hydrocarbon groups comprising from 1 to 18, such as from 1 to 12, further such as from 1 to 10, more further such as from 1 to 8, or from 1 to 6, or from 1 to 4, carbon atoms. Examples of alkyl groups comprising from 1 to 6 carbon atoms (i.e., C_1-6 alkyl) include, but not limited to, methyl, ethyl, 1-propyl or n-propyl (“n-Pr”), 2-propyl or isopropyl (“i-Pr”), 1-butyl or n-butyl (“n-Bu”), 2-methyl-1-propyl or isobutyl (“i-Bu”), 1-methylpropyl or s-butyl (“s-Bu”), 1,1-dimethylethyl ort-butyl (“t-Bu”), 1-pentyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, 2-methyl-1-butyl, 1-hexyl, 2-hexyl, 3-hexyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl and 3,3-dimethyl-2-butyl groups.

The term “cycloalkyl” refers to a hydrocarbon group selected from saturated cyclic hydrocarbon groups, comprising monocyclic and polycyclic (e.g., bicyclic and tricyclic) groups including fused, bridged or spiro cycloalkyl.

The term “aryl” used alone or in combination with other terms refers to a group selected from:

• • 5- and 6-membered carbocyclic aromatic rings, e.g., phenyl;
  • bicyclic ring systems such as 7- to 12-membered bicyclic ring systems, wherein at least one ring is carbocyclic and aromatic, e.g., naphthyl and indanyl; and,
  • tricyclic ring systems such as 10- to 15-membered tricyclic ring systems wherein at least one ring is carbocyclic and aromatic, e.g., fluorenyl.

The terms “aromatic hydrocarbon ring” and “aryl” are used interchangeable throughout the disclosure herein. In some embodiments, a monocyclic or bicyclic aromatic hydrocarbon ring has 5 to 10 ring-forming carbon atoms (i.e., C_5-10 aryl). Examples of a monocyclic or bicyclic aromatic hydrocarbon ring include, but not limited to, phenyl, naphth-1-yl, naphth-2-yl, anthracenyl, phenanthrenyl, and the like. In some embodiments, the aromatic hydrocarbon ring is a naphthalene ring (naphth-1-yl or naphth-2-yl) or phenyl ring. In some embodiments, the aromatic hydrocarbon ring is a phenyl ring.

The term “aryl-alkyl-” refers to an alkyl group as defined above which is further substituted by an aryl group. Examples of an aryl-alkyl group include aryl-C_1-8alkyl, such as phenylethyl, or phenylmethyl (benzyl).

The term “heteroaryl” refers to a group selected from:

• • 5-, 6- or 7-membered aromatic, monocyclic rings comprising at least one heteroatom, for example, from 1 to 4, or, in some embodiments, from 1 to 3, in some embodiments, from 1 to 2, heteroatoms, selected from nitrogen (N), sulfur (S) and oxygen (O), with the remaining ring atoms being carbon;
  • 7- to 12-membered bicyclic rings comprising at least one heteroatom, for example, from 1 to 4, or, in some embodiments, from 1 to 3, or, in other embodiments, 1 or 2, heteroatoms, selected from N, O, and S, with the remaining ring atoms being carbon and wherein at least one ring is aromatic and at least one heteroatom is present in the aromatic ring; and
  • 11- to 14-membered tricyclic rings comprising at least one heteroatom, for example, from 1 to 4, or in some embodiments, from 1 to 3, or, in other embodiments, 1 or 2, heteroatoms, selected from N, O, and S, with the remaining ring atoms being carbon and wherein at least one ring is aromatic and at least one heteroatom is present in an aromatic ring.

When the total number of S and O atoms in the heteroaryl group exceeds 1, those heteroatoms are not adjacent to one another. 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 aromatic heterocycle is not more than 1. When the heteroaryl group contains more than one heteroatom ring member, the heteroatoms may be the same or different. The nitrogen atoms in the ring(s) of the heteroaryl group can be oxidized to form N-oxides. The term “C-linked heteroaryl” as used herein means that the heteroaryl group is connected to the core molecule by a bond from a C-atom of the heteroaryl ring

The terms “aromatic heterocyclic ring” and “heteroaryl” are used interchangeable throughout the disclosure herein. In some embodiments, a monocyclic or bicyclic aromatic heterocyclic ring has 5-, 6-, 7-, 8-, 9- or 10-ring forming members with 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen (N), sulfur (S) and oxygen (O) and the remaining ring members being carbon. In some embodiments, the monocyclic or bicyclic aromatic heterocyclic ring is a monocyclic or bicyclic ring comprising 1 or 2 heteroatom ring members independently selected from nitrogen (N), sulfur (S) and oxygen (O). In some embodiments, the monocyclic or bicyclic aromatic heterocyclic ring is a 5- to 6-membered heteroaryl ring, which is monocyclic and which has 1 or 2 heteroatom ring members independently selected from nitrogen (N), sulfur (S) and oxygen (O). In some embodiments, the monocyclic or bicyclic aromatic heterocyclic ring is an 8- to 10-membered heteroaryl ring, which is bicyclic and which has 1 or 2 heteroatom ring members independently selected from nitrogen, sulfur and oxygen.

“Heterocyclyl”, “heterocycle” or “heterocyclic” are interchangeable and refer to a non-aromatic heterocyclyl group comprising one or more heteroatoms selected from nitrogen, oxygen or optionally oxidized sulfur as ring members, with the remaining ring members being carbon, including monocyclic, fused, bridged, and spiro ring, i.e., containing monocyclic heterocyclyl, bridged heterocyclyl, spiro heterocyclyl, and fused heterocyclic groups. The term “optionally oxidized sulfur” used herein refers to S, SO or SO₂.

Compounds disclosed herein may contain an asymmetric center and may thus exist as enantiomers. “Enantiomers” refer to two stereoisomers of a compound which are non-superimposable mirror images of one another. Where the compounds disclosed herein possess two or more asymmetric centers, they may additionally exist as diastereomers. Enantiomers and diastereomers fall within the broader class of stereoisomers. All such possible stereoisomers as substantially pure resolved enantiomers, racemic mixtures thereof, as well as mixtures of diastereomers are intended to be included. All stereoisomers of the compounds disclosed herein and/or pharmaceutically acceptable salts thereof are intended to be included. Unless specifically mentioned otherwise, the reference to one isomer applies to any of the possible isomers. Whenever the isomeric composition is unspecified, all possible isomers are included.

The term “substantially pure” as used herein means that the target stereoisomer contains no more than 35%, such as no more than 30%, further such as no more than 25%, even further such as no more than 20%, by weight of any other stereoisomer(s). In some embodiments, the term “substantially pure” means that the target stereoisomer contains no more than 10%, for example, no more than 5%, such as no more than 1%, by weight of any other stereoisomer(s).

When compounds disclosed herein contain olefinic double bonds, unless specified otherwise, such double bonds are meant to include both E and Z geometric isomers.

When compounds disclosed herein contain a di-substituted cyclohexyl or cyclobutyl group, substituents found on cyclohexyl or cyclobutyl ring may adopt cis and trans formations. Cis formation means that both substituents are found on the upper side of the 2 substituent placements on the carbon, while trans would mean that they were on opposing sides.

It may be advantageous to separate reaction products from one another and/or from starting materials. The desired product of each step or series of steps is separated and/or purified (hereinafter separated) to the desired degree of homogeneity by the techniques common in the art. Typically such separations involve multiphase extraction, crystallization from a solvent or solvent mixture, distillation, sublimation, or chromatography. Chromatography can involve any number of methods including, for example: reverse-phase and normal phase; size exclusion; ion exchange; high, medium and low pressure liquid chromatography methods and apparatus; small scale analytical; simulated moving bed (“SMB”) and preparative thin or thick layer chromatography, as well as techniques of small scale thin layer and flash chromatography. One skilled in the art will apply techniques most likely to achieve the desired separation.

“Diastereomers” refers to stereoisomers of a compound with two or more chiral centers but which are not mirror images of one another. Diastereomeric mixtures can be separated into their individual diastereomers on the basis of their physical chemical differences by methods well known to those skilled in the art, such as by chromatography and/or fractional crystallization. Enantiomers can be separated by converting the enantiomeric mixture into a diastereomeric mixture by reaction with an appropriate optically active compound (e.g., chiral auxiliary such as a chiral alcohol or Mosher's acid chloride), separating the diastereomers and converting (e.g., hydrolyzing) the individual diastereoisomers to the corresponding pure enantiomers. Enantiomers can also be separated by use of a chiral HPLC column.

“Pharmaceutically acceptable salts” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. A pharmaceutically acceptable salt may be prepared in situ during the final isolation and purification of the compounds disclosed herein, or separately by reacting the free base function with a suitable organic acid or by reacting the acidic group with a suitable base.

In addition, if a compound disclosed 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 product is a free base, an addition salt, such as a pharmaceutically acceptable addition salt, may be produced by dissolving the free base in a suitable organic solvent and/or water and treating the solution with an acid, in accordance with conventional procedures for preparing acid addition salts from base compounds. Those skilled in the art will recognize various synthetic methodologies that may be used without undue experimentation to prepare non-toxic pharmaceutically acceptable addition salts.

As defined herein, “a pharmaceutically acceptable salt thereof” includes salts of at least one compound of Formula (I), and salts of the stereoisomers of the compound of Formula (I), such as salts of enantiomers, and/or salts of diastereomers.

The terms “administration”, “administering”, “treating” and “treatment” herein, when applied to an animal, human, experimental subject, cell, tissue, organ, or biological fluid, mean contact of an exogenous pharmaceutical, therapeutic, diagnostic agent, or composition to the animal, human, subject, cell, tissue, organ, or biological fluid. Treatment of a cell encompasses contact of a reagent to the cell, as well as the contact of a reagent to a fluid, where the fluid is in contact with the cell. The term “administration” and “treatment” also means in vitro and ex vivo treatments, e.g., of a cell, by a reagent, diagnostic, binding compound, or by another cell. The term “subject” herein includes any organism, preferably an animal, more preferably a mammal (e.g., rat, mouse, dog, cat, and rabbit) and most preferably a human.

The term “effective amount” or “therapeutically effective amount” refers to an amount of the active ingredient, such as a compound that, when administered to a subject for treating a disease, or at least one of the clinical symptoms of a disease or disorder, is sufficient to affect such treatment for the disease, disorder, or symptom. The “therapeutically effective amount” can vary with the compound, the disease, disorder, and/or symptoms of the disease or disorder, severity of the disease, disorder, and/or symptoms of the disease or disorder, the age of the subject to be treated, and/or the weight of the subject to be treated. An appropriate amount in any given instance can be apparent to those skilled in the art or can be determined by routine experiments. In some embodiments, “therapeutically effective amount” is an amount of at least one compound and/or at least one stereoisomer thereof, and/or at least one pharmaceutically acceptable salt thereof disclosed herein effective to “treat” as defined above, a disease or disorder in a subject. In the case of combination therapy, the “therapeutically effective amount” refers to the total amount of the combination objects for the effective treatment of a disease, a disorder or a condition.

The pharmaceutical composition comprising the compound disclosed herein can be administrated via oral, inhalation, rectal, parenteral or topical administration to a subject in need thereof. For oral administration, the pharmaceutical composition may be a regular solid formulation such as tablets, powder, granule, capsules and the like, a liquid formulation such as water or oil suspension or other liquid formulation such as syrup, solution, suspension or the like; for parenteral administration, the pharmaceutical composition may be a solution, water solution, oil suspension concentrate, lyophilized powder or the like. Preferably, the formulation of the pharmaceutical composition is selected from a tablet, coated tablet, capsule, suppository, nasal spray or injection, more preferably tablet or capsule. The pharmaceutical composition can be a single unit administration with an accurate dosage. In addition, the pharmaceutical composition may further comprise additional active ingredients.

All formulations of the pharmaceutical composition disclosed herein can be produced by the conventional methods in the pharmaceutical field. For example, the active ingredient can be mixed with one or more excipients, then to make the desired formulation. The “pharmaceutically acceptable excipient” refers to conventional pharmaceutical carriers suitable for the desired pharmaceutical formulation, for example: a diluent, a vehicle such as water, various organic solvents, etc., a filler such as starch, sucrose, etc. a binder such as cellulose derivatives, alginates, gelatin and polyvinylpyrrolidone (PVP); a wetting agent such as glycerol; a disintegrating agent such as agar, calcium carbonate and sodium bicarbonate; an absorption enhancer such as quaternary ammonium compound; a surfactant such as hexadecanol; an absorption carrier such as Kaolin and soap clay; a lubricant such as talc, calcium stearate, magnesium stearate, polyethylene glycol, etc. In addition, the pharmaceutical composition further comprises other pharmaceutically acceptable excipients such as a decentralized agent, a stabilizer, a thickener, a complexing agent, a buffering agent, a permeation enhancer, a polymer, aromatics, a sweetener, and a dye.

The term “disease” refers to any disease, discomfort, illness, symptoms or indications, and can be interchangeable with the term “disorder” or “condition”.

Throughout this specification and the Aspects which follow, unless the context requires otherwise, the term “comprise”, and variations such as “comprises” and “comprising” are intended to specify the presence of the features thereafter, but do not exclude the presence or addition of one or more other features. When used herein the term “comprising” can be substituted with the term “containing”, “including” or sometimes “having”.

Throughout this specification and the Aspects which follow, the term “C_n-m” indicates a range which includes the endpoints, wherein n and m are integers and indicate the number of carbons. Examples include C_1-8, C_1-6, and the like.

Unless specifically defined elsewhere in this document, all other technical and scientific terms used herein have the meaning commonly understood by one of ordinary skill in the art to which this invention belongs.

EXAMPLES

The present invention is further exemplified, but not limited to, by the following examples that illustrate the invention.

In the following examples, the abbreviations below are used:

AcOH or HOAc      Acetic acid
aq.               Aqueous
BINAP             (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl)
BH3               Borane
Brine             Saturated aqueous sodium chloride solution
Boc2O             di(tert-butyl) carbonate
BSA               Bovine serum albumin
CDI               1,1′-Carbonyldiimidazole
DAST              Diethylaminosulfur trifluoride
DBN               1,5-Diazabicyclo[4.3.0]non-5-ene
DBU               1,8-Diazabicyclo[5.4.0]undec-7-ene
DCE               1,2-Dichloroethane
DCM               Dichloromethane
DMAP              4-Dimethylaminopyridine
CH3MgBr           Methyl magnesium bromide
DIPEA             N,N-Diisopropylethylamine
DMF               N,N-Dimethylformamide
DMAC              Dimethylacetamide
DMSO              Dimethyl sulfoxide
DPPA              Diphenylphosphoryl azide
EA                Ethyl acetate
EDCI              1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Hydrochloride
EDTA              Ethylenediaminetetraacetic acid
EtOH              Ethyl alcohol
h or hr           Hour
HATU              1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-
                  b]pyridinium 3-oxide hexafluorophosphate
Hex               Hexane
1H NMR            Proton Nuclear Magnetic Resonance
H2O2              Hydrogen peroxide
HOBt              Hydroxybenzotriazole
IPA (i-PrOH)      Isopropyl alcohol
KOAc              Potassium Acetate
LAH               Lithium aluminum hydride
LC-MS             Liquid chromatography-mass spectrometry
LDA               Lithium diisopropylamide
MeOH              Methanol
MsOH              Methanesulfonic acid
Min               Minutes
n-BuLi            n-Butyllithium
NaH               Sodium hydride
NaBH(OAc)3 (STAB) Sodium triacetoxyborohydride
NaBH3CN           Sodium cyanoborohydride
NH4Cl             Ammonium chloride
Pd/C              Palladium on carbon powder
Pd(dppf)Cl2       [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II)
Pd(PPh3)4         Tetrakis(triphenylphosphine)palladium(0)
Pd(OAc)2          Palladium acetate
Pd(OH)2/C         Palladium hydroxide on carbon powder
PE                Petroleum ether
pH                -lg(hydrogen ion concentration)
Prep-HPLC         Preparative high-pressure liquid chromatography
Prep-MPLC         Preparative medium pressure liquid chromatography
Prep-SFC          Preparative supercritical fluid chromatography
Pre-TLC           Preparative thin layer chromatography
p-TsOH            p-Toluenesulfonic acid
r.t. or RT        room temperature
sat.              Saturated
t-BuOK            Potassium tert-butoxide
TBS               tert-butyldimethylsilyl
THF               Tetrahydrofuran
TEA               Triethylamine
TFA               Trifluoroacetic acid
TsCl              4-methylbenzenesulfonyl chloride
TMSCN             Trimethylsilyl cyanide
TMSCF3            (Trifluoromethyl)trimethylsilane
TBAF              Tetrabutylammonium fluoride
TBSOTf            Trifluoromethanesulfonic acid tert-butyldimethylsilyl ester
TiCl4             Titanium tetrachloride
TIPT              propylphosphonic anhydride solution
TMSI              Trimethyliodosilane

The examples below are intended to be purely exemplary and should not be considered to be limiting in any way. Efforts have been made to ensure accuracy with respect to numbers used (for example, amounts, temperature, etc.), but some experimental errors and deviations should be accounted for. Unless indicated otherwise, temperature is in degrees Centigrade. Reagents were purchased from commercial suppliers such as Sigma-Aldrich, Alfa Aesar, or TCI, and were used without further purification unless indicated otherwise.

Unless indicated otherwise, the reactions set forth below were performed under a positive pressure of nitrogen or argon or with a drying tube in anhydrous solvents; the reaction flasks were fitted with rubber septa for the introduction of substrates and reagents via syringe; and glassware was oven dried and/or heat dried.

¹H NMR spectra were recorded on a Agilent instrument operating at 400 MHz. ¹HNMR spectra were obtained using CDCl₃, CD₂Cl₂, CD₃OD, D₂O, d₆-DMSO, d₆-acetone or (CD₃)₂CO as solvent and tetramethylsilane (0.00 ppm) or residual solvent (CDCl₃: 7.25 ppm; CD₃OD: 3.31 ppm; D₂0: 4.79 ppm; d₆-DMSO: 2.50 ppm; d6-acetone: 2.05; (CD₃)₂CO: 2.05) as the reference standard. When peak multiplicities are reported, the following abbreviations are used: s (singlet), d (doublet), t (triplet), q (quartet), qn (quintuplet), sx (sextuplet), m (multiplet), br (broadened), dd (doublet of doublets), dt (doublet of triplets). Coupling constants, when given, are reported in Hertz (Hz).

LC-MS spectrometer (Agilent 1260) Detector: MWD (190-400 nm), Mass detector: 6120 SQ

• • Mobile phase: A: acetonitrile with 0.10% Formic acid, B: water with 0.1% Formic acid
  • Column: Poroshell 120 EC-C18, 4.6×50 mm, 2.7 μm
  • Gradient method: Flow rate: 1.8 mL/min

Time (min)	A (%)	B (%)
0.00	5	95
1.5	95	5
2.0	95	5
2.1	5	95
3.0	5	95

Preparative HPLC was conducted on a column (150×21.2 mm ID, 5 μm, Gemini NX—C18) and (150×19 mm, 5 m, SunFire Prep C18 OBD™) at a different flow rate and injection volume, at room temperature and UV Detection at 214 nm and 254 nm.

Combi Flash was conducted on a column (C18 spherical 20-35 m) at a different flow rate and injection volume, at room temperature and UV Detection at 214 nm and 254 nm.

Preparation of Intermediates (Int):

Int A1: 5-((S)-2-amino-2-cyclohexylacetamido)-N-methyl-2-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-2,3-dihydro-1H-indene-2-carboxamide

Step 1: 2-amino-N-methyl-2,3-dihydro-1H-indene-2-carboxamide

The mixture of methyl 2-amino-2,3-dihydro-1H-indene-2-carboxylate (3.8 g, 20 mmol) in MeNH₂ solution (in EtOH, 33%, wt, 20 mL) was heated to 80° C. in a sealed tube for 4 hrs. The reaction was allowed to cool to ambient temperature and concentrated in vacuum to afford the title compound (3.7 g, yield: 97.32%)

Step 2: 2-amino-N-methyl-5-nitro-2,3-dihydro-1H-indene-2-carboxamide

To the mixture of H₂SO₄ (3 mL) and HNO₃ (3 mL) was added 2-amino-N-methyl-2,3-dihydro-1H-indene-2-carboxamide (3.7 g, 19.46 mmol, a solution in 6 mL HOAc) at 0° C. in batches slowly and stirred for 15 mins. The reaction mixture was poured into NaHCO₃ solution (aq, 200 mL) at 0° C. and then diluted with DCM (200 mL). The organic layer was separated, dried, concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=20/0 to 20/1) to afford the title compound. (3.28 g, yield: 71.56%).

Step 3: tert-butyl (2-(methylcarbamoyl)-5-nitro-2,3-dihydro-1H-inden-2-yl)carbamate

The mixture of 2-amino-N-methyl-5-nitro-2,3-dihydro-1H-indene-2-carboxamide (1.18 g, 5 mmol) and Boc₂O (1.15 g, 5.25 mmol) in DCM (50 mL) was stirred overnight. The mixture was quenched with brine (50 mL), separated and organic phase was dried over Na₂SO₄, concentrated in vacuum. The crude product was purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=50/1 to 20/1) to afford the tittle product (1.31 g, yield: 77.52%). MS (ESI, m/e) [M+1]⁺ 336.3.

Step 4: tert-butyl (5-amino-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-2-yl)carbamate

To the mixture of tert-butyl (2-(methylcarbamoyl)-5-nitro-2,3-dihydro-1H-inden-2-yl)carbamate (1.31 g, 3.90 mmol) and Pd/C (150 mg) in MeOH (50 mL) was bubbled with H₂ balloon and stirred overnight. The mixture was filtrated, concentrated in vacuum, purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=50/1 to 20/1) to afford the tittle product (1.06 g, yield: 88.99%). MS (ESI, m/e) [M+1]⁺ 306.0.

Step 5: tert-butyl (5-((S)-2-(((benzyloxy)carbonyl)amino)-2-cyclohexylacetamido)-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-2-yl)carbamate

The mixture of (S)-2-(((benzyloxy)carbonyl)amino)-2-cyclohexylacetic acid (909 mg, 3.0 mmol), tert-butyl (5-amino-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-2-yl)carbamate (915 mg, 3.0 mmol), HATU (1.14 g, 3.0 mmol) and TEA (606 mg, 6.0 mmol) in DCM (100 mL) was stirred at room temperature for 4 hrs. The mixture was quenched with aq. NaHCO₃ (150 mL), separated and organic phase was dried over Na₂SO₄, concentrated in vacuo. The crude product was purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=50/1 to 20/1) to afford the tittle product (1.41 g, yield: 80.67%). MS (ESI, m/e) [M+1]⁺ 579.3.

Step 6: benzyl ((1S)-2-((2-amino-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)carbamate

A mixture of tert-butyl (5-((S)-2-(((benzyloxy)carbonyl)amino)-2-cyclohexylacetamido)-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-2-yl)carbamate (5 g, 8.6 mmol) in DCM (50 mL) and TFA (20 mL) was stirred at 20° C. for 2 hrs. The reaction mixture was then concentrated under reduced pressure. The residue was diluted with H₂O (50 mL) and the aqueous phase was basified by Na₂CO₃ to pH ˜8-9. The mixture was extracted with EtOAc (50 mL×3). The combined organic layers were dried over Na₂SO₄, filtered and concentrated in vacuum to obtain benzyl ((1S)-2-((2-amino-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)carbamate (4 g, crude). MS (ESI, m/e) [M+H]⁺ 479.3.

Step 7: benzyl ((1S)-2-((2-(((1-(((tert-butoxycarbonyl)amino)methyl)cyclopropyl)methyl)amino)-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)carbamate

To a solution of benzyl ((1S)-2-((2-amino-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)carbamate (0.8 g, 1.7 mmol) and tert-butyl ((1-formylcyclopropyl)methyl)carbamate (0.5 g, 2.5 mmol) in DCM (15 mL) was added AcOH (0.2 g, 3.4 mmol) and NaBH(OAc)3 (0.931 g, 4.2 mmol) at 0° C. The mixture was stirred at 25° C. for 3 hrs. The reaction mixture was then diluted with aq·NaHCO₃ (20 mL) and extracted with DCM (10 mL×3), washed with brine, dried over Na₂SO₄, filtered and concentrated in vacuum. The crude product was purified by column chromatography on silica gel (eluent: Petroleum ether/Ethyl acetate (v/v)=100/1 to 0/1). Title compound (0.65 g, yield: 59%) was obtained.

Step 8: benzyl ((1S)-2-((2-(((1-(aminomethyl)cyclopropyl)methyl)amino)-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)carbamate

A mixture of benzyl ((1S)-2-((2-(((1-(((tert-butoxycarbonyl)amino)methyl)cyclopropyl)methyl)amino)-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)carbamate (0.65 g, 0.982 mmol) in HCl/EtOAc (10 mL) was stirred at 25° C. for 2 hrs. The reaction mixture was concentrated under reduced pressure to obtain benzyl ((1S)-2-((2-(((1-(aminomethyl)cyclopropyl)methyl)amino)-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)carbamate (0.55 g, HCl salt). MS (ESI, m/e) [M+H]⁺ 562.3.

Step 9: benzyl ((1S)-1-cyclohexyl-2-((2-(methylcarbamoyl)-2-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-2,3-dihydro-1H-inden-5-yl)amino)-2-oxoethyl)carbamate

To a solution of benzyl ((1S)-2-((2-(((1-(aminomethyl)cyclopropyl)methyl)amino)-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)carbamate (0.55 g, 0.98 mmol) in THF (10 mL) was added TEA (0.198 g, 1.9 mmol) and CDI (0.317 g, 1.9 mmol). The mixture was stirred at 60° C. for 8 hours. The reaction mixture was poured into ice/water (10 mL), extracted with EtOAc (10 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuum. The crude product was purified by column chromatography on silica gel (eluent: Petroleum ether/Ethyl acetate (v/v)=100/1 to 0/1) to obtain benzyl ((1S)-1-cyclohexyl-2-((2-(methylcarbamoyl)-2-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-2,3-dihydro-1H-inden-5-yl)amino)-2-oxoethyl)carbamate (0.46 g, yield: 80%).

Step 10: 5-((S)-2-amino-2-cyclohexylacetamido)-N-methyl-2-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-2,3-dihydro-1H-indene-2-carboxamide (Int A1)

To a solution of benzyl ((1S)-1-cyclohexyl-2-((2-(methylcarbamoyl)-2-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-2,3-dihydro-1H-inden-5-yl)amino)-2-oxoethyl)carbamate (0.41 g, 0.698 mmol) in MeOH (10 mL) and MeNH2·H2O (1 mL) was added Pd(OH)2 (0.1 g, 0.698 mmol). The mixture was stirred at 50° C. for 1 hr under H₂ (15 Psi). The reaction mixture was diluted with water (5 mL) and extracted with EtOAc (5 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to obtain 5-((S)-2-amino-2-cyclohexylacetamido)-N-methyl-2-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-2,3-dihydro-1H-indene-2-carboxamide (280 mg, yield: 87%). ¹H NMR (400 MHz, DMSO-d₆) δ ppm: 10.08-9.41 (m, 1H), 7.50 (s, 1H), 7.40-7.22 (m, 2H), 7.06 (d, J=8.4 Hz, 1H), 6.42 (s, 1H), 3.55-3.39 (m, 3H), 3.12-2.93 (m, 5H), 2.91-2.81 (m, 2H), 2.56 (d, J=4.8 Hz, 3H), 2.00-1.81 (m, 1H), 1.69 (d, J=10.0 Hz, 3H), 1.62-1.45 (m, 3H), 1.23-0.97 (m, 5H), 0.45-0.32 (m, 2H), 0.19-0.44 (m, 2H). MS (ESI, m/e) [M+H]⁺ 454.3.

Int A2: 5-((S)-2-amino-2-cyclohexylacetamido)-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-N-methyl-2,3-dihydro-1H-indene-2-carboxamide

Step 1: tert-butyl ((2R)-3-methyl-1-((2-(methylcarbamoyl)-5-nitro-2,3-dihydro-1H-inden-2-yl)amino)butan-2-yl)carbamate

To a solution of 2-amino-N-methyl-5-nitro-2,3-dihydro-1H-indene-2-carboxamide (10 g, 42.51 mmol) and (R)-tert-butyl (3-methyl-1-oxobutan-2-yl)carbamate (15.4 g, 78.52 mmol) in MeOH (100 mL) was added NaBH₃CN (5.17 g, 858.02 mmol). The mixture was stirred at 25° C. for 12 hrs. The reaction mixture was then concentrated under reduced pressure. The residue was diluted in water (50 mL) and extracted with DCM (50 mL×3). The combined organic layers were dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The crude product was purified by prep-MPLC (SiO₂ column, eluent: Petroleum ether/Ethyl acetate (v/v)=10/1 to 0/1) to obtain tert-butyl ((2R)-3-methyl-1-((2-(methylcarbamoyl)-5-nitro-2,3-dihydro-1H-inden-2-yl)amino)butan-2-yl)carbamate (13 g, yield: 73%). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 8.08 (d, J=10.0 Hz, 2H), 7.63-7.61 (m, 1H), 7.34 (d, J=8.0 Hz, 1H), 7.19 (d, J=3.2 Hz, 1H), 4.31 (s, 1H), 3.70-3.59 (m, 3H), 3.44 (s, 1H), 3.02-2.99 (m, 2H), 2.88 (d, J=4.8 Hz, 1H), 2.58-2.55 (m, 1H), 2.35-2.33 (m, 1H), 1.68-1.66 (m, 2H), 1.45 (s, 9H), 0.89-0.85 (m, 6H).

Step 2: 2-(((R)-2-amino-3-methylbutyl)amino)-N-methyl-5-nitro-2,3-dihydro-1H-indene-2-carboxamide

To a solution of tert-butyl ((2R)-3-methyl-1-((2-(methylcarbamoyl)-5-nitro-2,3-dihydro-1H-inden-2-yl)amino)butan-2-yl)carbamate (7.8 g, 18.55 mmol) in DCM (80 mL) was added TFA (10 mL). The mixture was stirred at 20° C. for 13 hrs. After concentrated to remove TFA, the reaction mixture was quenched by saturated NaHCO₃ (50 mL) and then extracted with DCM (100 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The crude product was purified by prep-MPLC (SiO₂ column, eluent: Petroleum ether/Ethyl acetate (v/v)=100/1 to 0/1) to obtain 2-(((R)-2-amino-3-methylbutyl)amino)-N-methyl-5-nitro-2,3-dihydro-1H-indene-2-carboxamide (4.5 g, yield: 76%). MS (ESI, m/e) [M+H]⁺ 321.2.

Step 3: 2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-N-methyl-5-nitro-2,3-dihydro-1H-indene-2-carboxamide

A mixture of 2-(((R)-2-amino-3-methylbutyl)amino)-N-methyl-5-nitro-2,3-dihydro-1H-indene-2-carboxamide (4 g, 12.48 mmol), TEA (0.5 mL) and CDI (3.04 g, 18.73 mmol) in THF (40 mL) was stirred at reflux for 1 hour. The reaction mixture was concentrated under reduced pressure and then diluted with water (50 mL) and extracted with DCM (50 mL×3). The combined organic layers were dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The crude product was purification by prep-MPLC (SiO₂ column, eluent: Petroleum ether/Ethyl acetate (v/v)=100/1 to 0/1) to obtain 2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-N-methyl-5-nitro-2,3-dihydro-1H-indene-2-carboxamide (3.5 g, yield: 80%). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 8.08 (d, J=7.2 Hz, 2H), 7.69 (s, 1H), 7.37-7.33 (m, 1H), 7.12 (s, 1H), 7.05 (s, 1H), 4.75 (s, 1H), 3.87-3.83 (m, 2H), 3.63-3.55 (m, 2H), 3.44-3.39 (m, 2H), 3.14-3.12 (m, 1H), 2.77 (d, J=7.6 Hz, 3H), 1.63-1.62 (m, 1H), 0.89-0.83 (m, 6H).

Step 4: 5-amino-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-N-methyl-2,3-dihydro-1H-indene-2-carboxamide

To a solution of 2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-N-methyl-5-nitro-2,3-dihydro-1H-indene-2-carboxamide (8.1 g, 25.58 mmol) in CH₃OH (80 mL) was added Pd/C (1 g). The reaction mixture was purged with H₂ for 3 times and hydrogenated under H₂ atmosphere (50 psi) at 50° C. for 12 hrs. The reaction mixture was filtered and the filtrate was concentrated in vacuum. The crude product was purification by prep-MPLC (SiO₂ column, eluent: Petroleum ether/Ethyl acetate (v/v)=100/1 to 0/1) to obtain 5-amino-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-N-methyl-2,3-dihydro-1H-indene-2-carboxamide (6.1 g, yield: 70%). MS (ESI, m/e) [M+H]⁺ 317.3.

Step 5: tert-butyl ((1S)-1-cyclohexyl-2-((2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-2-oxoethyl)carbamate

To a solution of 5-amino-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-N-methyl-2,3-dihydro-1H-indene-2-carboxamide (1.5 g, 4.74 mmol), TEA (719.59 mg, 7.11 mmol) and (S)-2-((tert-butoxycarbonyl)amino)-2-cyclohexylacetic acid (1.45 g, 5.69 mmol) in DCM (20 mL) was added HATU (2.16 g, 5.69 mmol) at 0° C. The mixture was stirred at 20° C. for 3 hrs. The reaction mixture was then quenched by H₂O (50 mL) and extracted with DCM (50 mL×3). The combined organic layers were dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The crude product was purified by prep-MPLC (SiO₂ column, eluent: Petroleum ether/Ethyl acetate (v/v)=100/1 to 1/1) to obtain tert-butyl ((1S)-1-cyclohexyl-2-((2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-2-oxoethyl)carbamate (2.5 g, yield: 95%). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 9.75 (s, 1H), 7.52-7.45 (m, 2H), 7.34-7.26 (m, 1H), 7.16-7.08 (m, 1H), 6.82-6.75 (m, 2H), 3.92-3.90 (m, 1H), 3.56-3.48 (m, 2H), 3.21-3.18 (m, 2H), 3.11-3.08 (m, 2H), 2.90-2.88 (m, 1H), 2.56 (d, J=4.4 Hz, 3H), 1.75-1.50 (m, 6H), 1.42 (s, 9H), 1.15-1.02 (m, 4H), 0.74-0.65 (m, 6H).

Step 6: 5-((S)-2-amino-2-cyclohexylacetamido)-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-N-methyl-2,3-dihydro-1H-indene-2-carboxamide (Int A2)

A solution of tert-butyl ((1S)-1-cyclohexyl-2-((2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-2-oxoethyl)carbamate (2.5 g, 4.5 mmol) in DCM (20 mL) and TFA (5 m) was stirred at 20° C. for 3 hrs. After concentrated in vacuum to remove TFA, the reaction mixture was quenched by saturated NaHCO₃ (50 mL) and extracted with DCM (100 mL×3). The combined organic layers were dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The crude product was purified by prep-MPLC (SiO₂ column, eluent: Petroleum ether/Ethyl acetate (v/v)=100/1 to 0/1) to obtain 5-((S)-2-amino-2-cyclohexylacetamido)-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-N-methyl-2,3-dihydro-1H-indene-2-carboxamide (1270 mg, yield: 62%). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.25 (s, 1H), 7.55-7.44 (m, 4H), 7.37-7.31 (m, 1H), 7.15 (d, J=8.0 Hz, 1H), 6.77 (d, J=11.2 Hz, 1H), 3.60-3.48 (m, 3H), 3.36-3.34 (m, 3H), 3.22-3.16 (m, 2H), 2.84-2.82 (m, 1H), 2.56 (d, J=4.4 Hz, 3H), 1.75-1.50 (m, 6H), 1.45 (s, 1H), 1.15-1.02 (m, 5H), 0.74-0.67 (m, 6H). MS (ESI, m/e) [M+H]⁺ 456.3.

Int A3: 5-((S)-2-amino-3,3-dicyclopropylpropanamido)-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-N-(o-tolyl)-2,3-dihydro-1H-indene-2-carboxamide

Step 1: methyl 5-amino-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2,3-dihydro-1H-indene-2-carboxylate

To a solution of methyl 2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-5-nitro-2,3-dihydro-1H-indene-2-carboxylate (5.9 g, 16.9 mmol, prepared by the procedure similar with 2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-N-methyl-5-nitro-2,3-dihydro-1H-indene-2-carboxamide as described in Int A2) in MeOH (60 mL) was added Raney Ni (0.6 g, 1.69 mmol) at r.t. under N₂. The mixture was hydrogenated under H₂ atmosphere (15 psi) at 60° C. for 1 hour. The reaction mixture was filtered through a celite pad and washed with MeOH (50 mL). The filtrate was concentrated in vacuum to obtain methyl 5-amino-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2,3-dihydro-1H-indene-2-carboxylate (2.5 g, crude), which was used directly for next step. MS (ESI, m/e) [M+H]⁺ 318.1.

Step 2: methyl 5-((S)-2-(((benzyloxy)carbonyl)amino)-3,3-dicyclopropylpropanamido)-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2,3-dihydro-1H-indene-2-carboxylate

To a solution of methyl 5-amino-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2,3-dihydro-1H-indene-2-carboxylate (2.5 g), DIEA (3.05 g, 23.6 mmol) and (S)-2-(((benzyloxy)carbonyl)amino)-3,3-dicyclopropylpropanoic acid (2.39 g, 7.88 mmol) in DCM (25 mL) was added HATU (3.0 g, 7.88 mmol) at 0° C. The mixture was stirred at r.t. for 12 hrs. The reaction mixture was diluted with water (30 mL) and then extracted with DCM (30 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The crude product was purified by column chromatography on silica gel(eluent: Petroleum ether/Ethyl acetate (v/v)=100/1 to 0/1) to obtain methyl 5-((S)-2-(((benzyloxy)carbonyl)amino)-3,3-dicyclopropylpropanamido)-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2,3-dihydro-1H-indene-2-carboxylate (2.5 g, yield: 53%). MS (ESI, m/e) [M+H]⁺ 603.3.

Step 3: 5-((S)-2-(((benzyloxy)carbonyl)amino)-3,3-dicyclopropylpropanamido)-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2,3-dihydro-1H-indene-2-carboxylic acid

To a solution of methyl 5-((S)-2-(((benzyloxy)carbonyl)amino)-3,3-dicyclopropylpropanamido)-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2,3-dihydro-1H-indene-2-carboxylate (2.5 g, 4.13 mmol) in THF (47 mL) was added H₂O (10 mL), LiOH·H₂O (654 mg, 8.26 mmol) under N₂. The mixture was stirred at r.t. for 2 hours. The reaction mixture was diluted with HCl acid (30 mL, 0.5M) under stirring and then extracted with EtOAc (35 mL×3). The combined organic phase was washed with brine (40 mL), dried with anhydrous Na₂SO₄, filtered and concentrated in vacuum to obtain the 5-((S)-2-(((benzyloxy)carbonyl)amino)-3,3-dicyclopropylpropanamido)-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2,3-dihydro-1H-indene-2-carboxylic acid (1.0 g, yield: 50%). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 12.5 (s, 1H), 9.84 (s, 1H), 7.23-7.53 (m, 8H), 7.13-7.11 (m, 1H), 6.75 (d, J=2.4 Hz, 1H), 5.06 (s, 2H), 4.29-4.44 (m, 1H), 3.42-3.52 (m, 2H), 3.36 (s, 2H), 3.16-3.24 (m, 1H), 3.04-3.13 (m, 1H), 1.50-1.47 (m, 1H), 0.70-0.92 (m, 9H), 0.08-0.61 (m, 10H). MS found: [M+H]⁺ 589.4.

Step 4: benzyl ((2S)-1,1-dicyclopropyl-3-((2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(o-tolylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)carbamate

To a solution of 5-((S)-2-(((benzyloxy)carbonyl)amino)-3,3-dicyclopropylpropanamido)-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2,3-dihydro-1H-indene-2-carboxylic acid (0.15 g, 254.80 umol) in DCM (5 mL) was added o-toluidine (0.027 g, 0.255 mmol), DIEA (65.86 mg, 509.60 umol) and HATU (116.24 mg, 305.76 umol) at 0° C. The mixture was stirred at r.t. for 12 hrs. The reaction mixture was diluted with H₂O (5 mL) and then extracted with DCM (5 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The crude product was purified by prep-TLC (silica gel, eluent: Petroleum ether/Ethyl acetate (v/v)=5:1, R_f=0.1) to obtain benzyl ((2S)-1,1-dicyclopropyl-3-((2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(o-tolylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)carbamate (0.105 g, yield: 61%).

Step 5: 5-((S)-2-amino-3,3-dicyclopropylpropanamido)-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-N-(o-tolyl)-2,3-dihydro-1H-indene-2-carboxamide (Int A3)

To a solution of benzyl ((2S)-1,1-dicyclopropyl-3-((2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(o-tolylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)carbamate (0.105 g, 0.155 mmol) in MeOH (1 mL) and MeNH2·H2O (0.1 mL) was added Pd(OH)2/C (0.1 g, 0.155 mmol) at 20° C. under H₂. The mixture was stirred at 50° C. for 1 hour under H₂ (20 Psi) atmosphere. The reaction mixture was filtered, and the filtrate was concentrated in vacuum. The crude product was purified by prep-TLC (silica gel, eluent: Ethyl acetate/MeOH (v/v)=10/1, R_f=0.2) obtain the title compound Int A3 (65 mg, yield: 77%). MS found: [M+H]⁺ 544.5.

Another key intermediates with carboxamide group at 2-position of 2,3-dihydro-1H-indene core fragment were synthesized according to the similar method/procedure as intermediate IntA1 or IntA2 or IntA3, which are known to those skilled in this art; the diverse materials of aldehyde and amino acid were also listed in Table.

		Protected Amino
Int	Structure	acid
A4
A5
A6
A7
A8
A9
A10
A11
A12
A13
A14
A15
A16
A17
A18
A19
A20
A21
A22
A23
A24
A25
A26
A27
A28
A29
A30
A31
A32
A33
A34
A35
A36
A37
A38
A39
A40
A41
A42
A43
A44
A45
A46
A47
A48
A49
A50
A51
A52
A53
A54
A55
A56
A57
A58
A59
A60
A61
A62
A63
A64
A65
A66
A67
A68
A69
A70
A71
A72
A73
A74
A75
A76
A77
A78
A79
A80
A81
A82
A83
	Int	Aldehyde	Data
	A4		MS (ESI, m/e) [M + 1]+ 428.2
	A5		MS (ESI, m/e) [M + 1]+ 460.3
	A6		MS (ESI, m/e) [M + 1]+ 456.3
	A7		MS (ESI, m/e) [M + 1]+ 434.4.
	A8		MS (ESI, m/e) [M + 1]+ 414.3
	A9		MS (ESI, m/e) [M + 1]+ 414.2
	A10		MS (ESI, m/e) [M + 1]+ 442.3
	A11		MS (ESI, m/e) [M + 1]+ 439.2
	A12		MS (ESI, m/e) [M + 1]+ 428.2
	A13		MS (ESI, m/e) [M + 1]+ 442.3
	A14		MS (ESI, m/e) [M + 1]+ 470.3
	A15		MS (ESI, m/e) [M + 1]+ 492.2.
	A16		MS (ESI, m/e) [M + 1]+ 468.2.
	A17		MS (ESI, m/e) [M + 1]+ 464.3.
	A18		MS (ESI, m/e) [M + 1]+ 486.3.
	A19		MS (ESI, m/e) [M + 1]+ 633.4.
	A20		MS (ESI, m/e) [M + 1]+ 510.2.
	A21		MS (ESI, m/e) [M + 1]+ 458.3.
	A22		MS (ESI, m/e) [M + 1]+ 484.3
	A23		MS (ESI, m/e) [M + 1]+ 470.3
	A24		MS (ESI, m/e) [M + 1]+ 510.4.
	A25		MS (ESI, m/e) [M + 1]+ 530.3.
	A26		MS (ESI, m/e) [M + 1]+ 474.3
	A27		MS (ESI, m/e) [M + 1]+ 496.3
	A28		MS (ESI, m/e) [M + 1]+ 482.3
	A29		MS (ESI, m/e) [M + 1]+ 468.4.
	A30		MS (ESI, m/e) [M + 1]+ 442.2.
	A31		MS (ESI, m/e) [M + 1]+ 490.3.
	A32		MS (ESI, m/e) [M + 1]+ 442.2.
	A33		MS (ESI, m/e) [M + 1]+ 518.4.
	A34		MS (ESI, m/e) [M + 1]+ 484.3.
	A35		MS (ESI, m/e) [M + 1]+ 470.3.
	A36		MS (ESI, m/e) [M + 1]+ 470.3.
	A37		MS (ESI, m/e) [M + 1]+ 466.3.
	A38		MS (ESI, m/e) [M + 1]+ 468.3.
	A39		MS (ESI, m/e) [M + 1]+ 508.3.
	A40		MS (ESI, m/e) [M + 1]+ 482.4.
	A41		MS (ESI, m/e) [M + 1]+ 482.3
	A42		MS (ESI, m/e) [M + 1]+ 512.5.
	A43		MS (ESI, m/e) [M + 1]+ 504.3.
	A44		MS (ESI, m/e) [M + 1]+ 428.3.
	A45		MS (ESI, m/e) [M + 1]+ 529.3.
	A46		MS (ESI, m/e) [M + 1]+ 519.4
	A47		MS (ESI, m/e) [M + 1]+ 482.1.
	A48		MS (ESI, m/e) [M + 1]+ 468.3
	A49		MS (ESI, m/e) [M + 1]+ 468.3
	A50		MS (ESI, m/e) [M + 1]+ 454.3.
	A51		MS (ESI, m/e) [M + 1]+ 536.5.
	A52		MS (ESI, m/e) [M + 1]+ 538.3.
	A53		MS (ESI, m/e) [M + 1]+ 538.1.
	A54		MS (ESI, m/e) [M + 1]+ 538.3.
	A55		MS (ESI, m/e) [M + 1]+ 498.0.
	A56		MS (ESI, m/e) [M + 1]+ 490.3
	A57		MS (ESI, m/e) [M + 1]+ 610.4.
	A58		MS (ESI, m/e) [M + 1]+ 628.4.
	A59		MS (ESI, m/e) [M + 1]+ 572.3.
	A60		MS (ESI, m/e) [M + 1]+ 568.3.
	A61		MS (ESI, m/e) [M + 1]+ 560.5.
	A62		MS (ESI, m/e) [M + 1]+ 564.4.
	A63		MS (ESI, m/e) [M + 1]+ 632.3.
	A64		MS (ESI, m/e) [M + 1]+ 544.4.
	A65		MS (ESI, m/e) [M + 1]+ 548.4.
	A66		MS (ESI, m/e) [M + 1]+ 564.3.
	A67		MS (ESI, m/e) [M + 1]+ 598.2.
	A68		MS (ESI, m/e) [M + 1]+ 598.3.
	A69		MS (ESI, m/e) [M + 1]+ 604.2.
	A70		MS (ESI, m/e) [M + 1]+ 580.3.
	A71		MS (ESI, m/e) [M + 1]+ 564.3.
	A72		MS (ESI, m/e) [M + 1]+ 598.4.
	A73		MS (ESI, m/e) [M + 1]+ 530.3.
	A74		MS (ESI, m/e) [M + 11]+ 565.3.
	A75		MS (ESI, m/e) [M + 1]+ 582.3.
	A76		MS (ESI, m/e) [M + 1]+ 524.4.
	A77		MS (ESI, m/e) [M + 1]+ 548.4.
	A78		MS (ESI, m/e) [M + 1]+ 522.3.
	A79		MS (ESI, m/e) [M + 1]+ 555.3.
	A80		MS (ESI, m/e) [M + 1]+ 565.4.
	A81		MS (ESI, m/e) [M + 1]+ 537.3.
	A82		MS (ESI, m/e) [M + 1]+ 572.4.
	A83		MS (ESI, m/e) [M + 1]+ 558.4.

The protected amino acid or aldehyde are either commercially available, known in the literature or can be synthesized as outlined in indicated preparation.

Int B1: 5-(5-amino-2-(1H-benzo[d]imidazol-2-yl)-2,3-dihydro-1H-inden-2-yl)-5,7-diazaspiro[2.5]octan-6-one

Step 1: 5-nitro-2-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-2,3-dihydro-1H-indene-2-carboxylic acid

To a solution of N-methyl-5-nitro-2-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-2,3-dihydro-1H-indene-2-carboxamide (2.1 g, 6.1 mol, prepared by the procedure similar with 2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-N-methyl-5-nitro-2,3-dihydro-1H-indene-2-carboxamide as described in IntA2) in DCM (15 mL) was added TFA (5 mL) and stirred at room temperature for 4 hrs. The reaction mixture was cooled to r.t. and concentrated to remove TFA and solvent in vacuum. The residue was diluted with DCM (50 mL), washed with saturated NaHCO₃ (20 mL), then saturated NH4Cl (20 mL). The organic solution was dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum to obtain 5-nitro-2-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-2,3-dihydro-1H-indene-2-carboxylic acid (2 g, yield: 98%). MS found: [M+H]⁺ 332.4.

Step 2: N-(2-aminophenyl)-5-nitro-2-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-2,3-dihydro-1H-indene-2-carboxamide

To a solution of 5-nitro-2-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-2,3-dihydro-1H-indene-2-carboxylic acid (0.5 g, 1.51 mmol), benzene-1,2-diamine (0.26 g, 1.51 mmol) and TEA (0.3 g, 3 mmol) in DCM (10 mL) was added HATU (0.0.65 g, 1.7 mmol) at 0° C. The mixture was stirred at room temperature for 4 hrs. The reaction mixture was diluted with water (15 mL), extracted with EtOAc (20 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: Petroleum ether/Ethyl acetate (v/v)=100/1 to 1/1 to obtain N-(2-aminophenyl)-5-nitro-2-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-2,3-dihydro-1H-indene-2-carboxamide (0.18 g, yield: 28%). MS found: [M+H]⁺ 422.4.

Step 3: 5-(2-(1H-benzo[d]imidazol-2-yl)-5-nitro-2,3-dihydro-1H-inden-2-yl)-5,7-diazaspiro[2.5]octan-6-one

A solution of N-(2-aminophenyl)-5-nitro-2-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-2,3-dihydro-1H-indene-2-carboxamide (0.18 g, 0.45 mmol) in AcOH (8 mL) was heated to 50° C. and stirred for 4 hrs. The reaction mixture was diluted with water (15 mL), extracted with EtOAc (20 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The crude product was purified by column chromatography on silica gel (eluent: Petroleum ether/Ethyl acetate (v/v)=50/1 to 5/1) to obtain 5-(2-(1H-benzo[d]imidazol-2-yl)-5-nitro-2,3-dihydro-1H-inden-2-yl)-5,7-diazaspiro[2.5]octan-6-one (80 mg, yield: 44%). MS found: [M+H]⁺ 404.2.

Step 4: 5-(5-amino-2-(1H-benzo[d]imidazol-2-yl)-2,3-dihydro-1H-inden-2-yl)-5,7-diazaspiro[2.5]octan-6-one (Int B1)

To a solution of 5-(2-(1H-benzo[d]imidazol-2-yl)-5-nitro-2,3-dihydro-1H-inden-2-yl)-5,7-diazaspiro[2.5]octan-6-one (80 mg, 0.09 mmol) in MeOH (10 mL) was added Raney-Ni (11 mg) and NH3·H₂O (1 mL) under N₂ The suspension was degassed under vacuum and purge with H₂ three times. The mixture was stirred at 50° C. under H₂ atmosphere for 1 hour. The reaction mixture was filtered and concentrated in vacuum to obtain 5-(5-amino-2-(1H-benzo[d]imidazol-2-yl)-2,3-dihydro-1H-inden-2-yl)-5,7-diazaspiro[2.5]octan-6-one (70 mg, yield: 54%). ¹H NMR (400 MHz, DMSO-d6) δ ppm 11.89 (s, 1 H), 7.55-7.38 (m, 2H), 7.07 (s, 2H), 6.79 (d, J=6.8 Hz, 1H), 6.47-6.11 (m, 3H), 4.79 (s, 2H), 4.06-3.82 (m, 2H), 3.27-3.09 (m, 4H), 2.86 (d, J=7.2 Hz, 2H), 0.49-0.27, 4H). [M+H]⁺ 374.2.

Int B2: 5-(5-amino-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-yl)-5,7-diazaspiro[2.5]octan-6-one

Step 1: Ethyl 5-bromo-2-((tert-butoxycarbonyl)amino)-2,3-dihydro-1H-indene-2-carboxylate

To a solution of ethyl 2-amino-5-bromo-2,3-dihydro-1H-indene-2-carboxylate (4 g, 14.1 mmol) in DCM (60 mL) was added Boc₂O (7.7 g, 35.3 mmol). The mixture was heated to reflux and stirred for 15 hrs. The reaction mixture was cooled to room temperature and concentrated. The residue was purified by column chromatography on silica gel (eluent: EtOAc/PE (v/v)=1/5) to obtain ethyl 5-bromo-2-((tert-butoxycarbonyl)amino)-2,3-dihydro-1H-indene-2-carboxylate (4.8 g, yield: 91%). MS (ESI) m/e [M−56+1]⁺328.1.

Step 2: 5-bromo-2-((tert-butoxycarbonyl)amino)-2,3-dihydro-1H-indene-2-carboxylic acid

To a solution of Ethyl 5-bromo-2-((tert-butoxycarbonyl)amino)-2,3-dihydro-1H-indene-2-carboxylate (3.45 g, 9.0 mmol) in THF (45 mL) was added NaOH solution (1.44 g in 15 mL H₂O) dropwise under stirring at room temperature. The resulting mixture was heated to 55° C. and stirred for 16 hrs. The reaction mixture was cooled to room temperature and concentrated in vacuum. The residue was diluted with water and the mixture was adjusted to pH˜5 with HCl acid (1 N), and was then extracted with EtOAc (50×3 mL). The organic layer was washed with brine, dried and concentrated in vacuum. The crude product was stirred in EtOAc/PE (1:1) for 10 min at room temperature. The solid was collected by filtration and dried in vacuum to obtain 5-bromo-2-((tert-butoxycarbonyl)amino)-2,3-dihydro-1H-indene-2-carboxylic acid (3 g, yield: 93%). MS (ESI) m/e [M+23]⁺378.1.

Step 3: Tert-butyl (5-bromo-2-(methoxy(methyl)carbamoyl)-2,3-dihydro-1H-inden-2-yl)carbamate

To a solution of 5-bromo-2-((tert-butoxycarbonyl)amino)-2,3-dihydro-1H-indene-2-carboxylic acid (2.3 g, 6.5 mmol) in DCM (50 mL) was added N,O-dimethylhydroxylamine hydrochloride (698 mg, 7.1 mmol) and HATU (2.7 g, 7.1 mmol), DIPEA (3.3 g, 25.9 mmol) dropwise at room temperature. The resulting mixture was stirred at room temperature for 2 hrs. The reaction mixture was diluted with EtOAc. The organic layer was washed with saturated NaHCO₃ solution (aq.) and brine, dried and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: EtOAc/PE (v/v)=1/2) to obtain tert-butyl (5-bromo-2-(methoxy(methyl)carbamoyl)-2,3-dihydro-1H-inden-2-yl)carbamate (2.3 g, yield: 88%). MS (ESI) m/e [M−56+1]+343.2.

Step 4: Tert-butyl (2-acetyl-5-bromo-2,3-dihydro-1H-inden-2-yl)carbamate

To a solution of tert-butyl (5-bromo-2-(methoxy(methyl)carbamoyl)-2,3-dihydro-1H-inden-2-yl)carbamate (1.55 g, 3.9 mmol) in THF (25 mL) was added CH₃MgCl (4 mL, 11.7 mmol) at below −10° C. under N₂ atmosphere. The resulting mixture was stirred for 1 hour at 0° C. The reaction mixture was poured into saturated aq. NH₄Cl (30 mL) at 0° C. and then extracted with EtOAc (30 mL×3). The combined organic layer was washed with brine, dried and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: EtOAc/PE (v/v)=1/6) to obtain tert-butyl (2-acetyl-5-bromo-2,3-dihydro-1H-inden-2-yl)carbamate (1.3 g, yield: 94%). MS (ESI) m/e [M+23]⁺376.1.

Step 5: Tert-butyl (5-bromo-2-(1-((trimethylsilyl)oxy)vinyl)-2,3-dihydro-1H-inden-2-yl)carbamate

Tert-butyl (2-acetyl-5-bromo-2,3-dihydro-1H-inden-2-yl)carbamate (1.1 g, 3.1 mmol) was dissolved into THF (15 mL) and cooled to −70° C. under N₂ atmosphere. To this solution was added LDA (3.1 mL, 6.2 mmol) dropwise with stirring at −70° C. under N₂ atmosphere. After the resulting mixture was stirred for 30 min, TMSCl (680 mg, 6.2 mmol) was added at −70° C. After further stirred at −60° C. for 1 hour, the reaction mixture was quenched by NH₄Cl (aq.) below −20° C. and then was diluted with EtOAc. The organic layer was separated, washed with water and brine, dried and concentrated in vacuum to obtain crude product (1.5 g), which used in next step directly.

Step 6: Tert-butyl (5-bromo-2-(2-bromoacetyl)-2,3-dihydro-1H-inden-2-yl)carbamate

To a solution of tert-butyl (5-bromo-2-(1-((trimethylsilyl)oxy)vinyl)-2,3-dihydro-1H-inden-2-yl)carbamate (1.5 g, crude) in THF (20 mL) was added NBS (625 mg, 3.5 mmol) in several portions at 0° C. The mixture was stirred for 1 hour at 0° C. The reaction mixture was quenched by NaHCO₃ (aq.) and diluted with EtOAc (30 mL). The organic layer was separated, washed with water and brine, dried and concentrated. The residue was purified by column chromatography on silica gel (eluent: EtOAc/PE (v/v)=1/7) to obtain tert-butyl (5-bromo-2-(2-bromoacetyl)-2,3-dihydro-1H-inden-2-yl)carbamate (740 mg, yield: 55% for two steps). MS (ESI) m/e [M+23]⁺ 456.1.

Step 7: Tert-butyl (5-bromo-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-yl)carbamate

A solution of Tert-butyl (5-bromo-2-(2-bromoacetyl)-2,3-dihydro-1H-inden-2-yl)carbamate (740 mg, 1.72 mmol) and pyridin-2-amine (162 mg, 1.72 mmol) in MeOH (10 mL) was heated to 80° C. and stirred for 24 h under N₂ atmosphere. The reaction mixture was cooled to room temperature and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: EtOAc/PE (v/v)=1/2) to obtain tert-butyl (5-bromo-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-yl)carbamate (250 mg, yield: 34%). MS (ESI) m/e [M+1]⁺ 428.2.

Step 8: 5-bromo-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-amine

To a solution of tert-butyl (5-bromo-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-yl)carbamate (250 mg, 0.59 mmol) in DCM (16 mL) was added HCl (4N in dioxane, 4 mL) dropwise at room temperature. The resulting mixture was stirred for 2 hrs at room temperature. The reaction mixture was then concentrated in vacuum. 5-bromo-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-amine (180 mg, crude) as HCl salts. MS (ESI) m/e [M+1]⁺ 328.1.

Step 9: Tert-butyl ((1-(((5-bromo-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-yl)amino)methyl)cyclopropyl)-methyl)carbamate

A mixture of 5-bromo-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-amine (180 mg, 0.55 mmol) and tert-butyl ((1-formylcyclopropyl)methyl)carbamate (154 mg, 0.77 mmol) in DCM (10 mL) was stirred at room temperature for 1 hour. To this mixture was then added NaBH₃CN (351 mg, 1.66 mmol) in portions at 0° C. The resulting mixture was stirred at room temperature overnight. The reaction mixture was quenched by NaHCO₃ (aq.) and extracted with EtOAc (30 mL). The organic layer was washed with brine, dried and concentrated in vacuum. The residue was purified by Prep-TLC (eluent: DCM/EtOAc (v/v)=1/1) to obtain tert-butyl ((1-(((5-bromo-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-yl)amino)methyl)cyclopropyl)-methyl)carbamate (200 mg, yield: 67% for two steps). MS (ESI) m/e [M+1]⁺ 511.3.

Step 10: N-((1-(aminomethyl)cyclopropyl)methyl)-5-bromo-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-amine

To a solution of tert-butyl ((1-(((5-bromo-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-yl)amino)methyl)cyclopropyl)-methyl)carbamate (200 mg, 0.39 mmol) in DCM (9 mL) was added HCl (4N in dioxane, 3 mL) dropwise at 0° C. The resulting mixture was stirred for 2 h at room temperature. The reaction mixture was then concentrated and N-((1-(aminomethyl)cyclopropyl)methyl)-5-bromo-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-amine HCl salts (200 mg, crude) was obtained, which used in next step directly. MS (ESI) m/e [M+1]⁺ 411.2.

Step 11: 5-(5-bromo-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-yl)-5,7-diazaspiro[2.5]octan-6-one

To a solution of N-((1-(aminomethyl)cyclopropyl)methyl)-5-bromo-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-amine (200 mg) and TEA (1 mL) in THF (10 mL) was added CDI (198 mg, 1.22 mmol). The mixture was heated to 60° C. and stirred for 1 hour. The reaction mixture was cooled to room temperature, diluted with EtOAc, washed with water and brine, dried and concentrated in vacuum. The crude product was purified by Prep-TLC (eluent: DCM/MeOH (v/v)=15/1) to obtain 5-(5-bromo-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-yl)-5,7-diazaspiro[2.5]octan-6-one (100 mg, yield: 58% for two steps). MS (ESI) m/e [M+1]⁺ 437.2.

Step 12: 5-(5-((diphenylmethylene)amino)-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-yl)-5,7-diazaspiro[2.5]octan-6-one

To a solution of 5-(5-bromo-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-yl)-5,7-diazaspiro[2.5]octan-6-one (100 mg, 0.23 mmol) in dioxane (15 mL) were added diphenylmethanimine (62.3 mg, 0.34 mmol), Pd₂dba₃ (21 mg, 0.02 mmol), Xantphos (27 mg, 0.04 mmol) and Cs₂CO₃ (150 mg, 0.46 mmol). The mixture was degassed with N₂, heated to 100° C. and then stirred for 6 hrs under N₂ atmosphere. The reaction mixture was cooled to room temperature and diluted with DCM/MeOH (v/v=15/1). After solids were filtered out, the filtrate was concentrated and purified by Prep-TLC (eluent: DCM/MeOH (v/v)=20/1) to obtain 5-(5-((diphenylmethylene)amino)-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-yl)-5,7-diazaspiro[2.5]octan-6-one (58 mg, yield: 47%). MS (ESI) m/e [M+1]+538.4.

Step 13: 5-(5-amino-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-yl)-5,7-diazaspiro[2.5]octan-6-one (Int B2)

To a solution of 5-(5-((diphenylmethylene)amino)-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-yl)-5,7-diazaspiro[2.5]octan-6-one (58 mg, 0.11 mmol) in THF (5 mL) was added HCl (3N, 1 mL) at room temperature and stirred for 30 min. The resulting reaction mixture was poured into saturated aq. NaHCO₃ and then extracted with EA (30×3 mL). The combined organic layer were washed with brine, dried, filtered and concentrated in vacuum. The residue was purified by Prep-TLC (eluent: DCM/MeOH (v/v)=10/1) to obtain 5-(5-amino-2-(imidazo[1,2-a]pyridin-2-yl)-2,3-dihydro-1H-inden-2-yl)-5,7-diazaspiro[2.5]octan-6-one (22 mg, yield: 55%). MS (ESI) m/e [M+1]⁺ 374.3.

Int C1: (4S)-1-(1-(6-amino-2,3-dihydrobenzofuran-2-yl)ethyl)-4-(trifluoromethyl)imidazolidin-2-one

Step 1: 1-(6-nitrobenzofuran-2-yl)ethan-1-one

To a solution of 2-hydroxy-4-nitrobenzaldehyde (2 g, 12 mmol) and 1-chloropropan-2-one (1.1 g, 12 mmol) in CH₃CN (20 mL) was added K₂CO₃ (3.3 g, 24 mmol). The mixture was stirred for 4 hrs at room temperature. The reaction mixture was poured into water (40 mL) and then extracted with EtOAc (20 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: PE/EA (v/v)=100/1 to 10/1) to obtain 1-(6-nitrobenzofuran-2-yl)ethanone (0.61 g, yield: 25%). MS (ESI) m/e [M+1]⁺ 206.2.

Step 2: (S)-1,1,1-trifluoro-3-((1-(6-nitrobenzofuran-2-yl)ethylidene)amino)propan-2-amine

To a solution of 1-(6-nitrobenzofuran-2-yl)ethanone (0.4 g, 1.9 mmol) and (S)-3,3,3-trifluoropropane-1,2-diamine hydrochloride (0.164 g, 2.9 mmol) in DCM (10 mL) was added TEA (0.101 g, 19.5 mmol) and 4A MS (1 g). The mixture was stirred at 45° C. for 3 hrs. After the reaction mixture was filtered, the filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluent: PE/EA (v/v)=100/1 to 0/1) to give (S)-3,3,3-trifluoro-N1-(1-(6-nitrobenzofuran-2-yl)ethylidene)propane-1,2-diamine (0.5 g, yield: 81%). MS (ESI) m/e [M+1]+316.1.

Step 3: (2S)-3,3,3-trifluoro-N1-(1-(6-nitrobenzofuran-2-yl)ethyl)propane-1,2-diamine

To a solution of (S)-3,3,3-trifluoro-N1-(1-(6-nitrobenzofuran-2-yl)ethylidene)propane-1,2-diamine (0.5 g, 1.6 mmol) in MeOH (10 mL) was added NaBH₃CN (1 g, 16 mmol). The mixture was stirred at 70° C. for 12 hrs. The mixture was poured into water (20 mL) and then extracted with EtOAc (10 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The residue was purified The crude product was purified by column chromatography on silica gel (eluent: DCM/CH₃OH(v/v)=100/1 to 10/1) to obtain (2S)-3,3,3-trifluoro-N1-(1-(6-nitrobenzofuran-2-yl)ethyl)propane-1,2-diamine (0.32 g, yield: 64%). MS (ESI) m/e [M+1]+318.2.

Step 4: (4S)-1-(1-(6-nitrobenzofuran-2-yl)ethyl)-4-(trifluoromethyl)imidazolidin-2-one

To a solution of (2S)-3,3,3-trifluoro-N1-(1-(6-nitrobenzofuran-2-yl)ethyl)propane-1,2-diamine (1.2 g, 3.8 mmol) in THF (15 mL) was added CDI (0.92 g, 5.7 mmol) and TEA (0.5 mL) at 20° C. The mixture was stirred at 60° C. for 6 hrs. The reaction mixture was diluted with EtOAc (30 mL) and then were washed with brine. The organic layer was dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: PE/EAE (v/v)=100/1 to 10/1) to obtain (4S)-1-(1-(6-nitrobenzofuran-2-yl)ethyl)-4-(trifluoromethyl)imidazolidin-2-one (0.34 g, yield: 26%). MS (ESI) m/e [M+1]⁺ 344.3.

Step 5: (4S)-1-(1-(6-amino-2,3-dihydrobenzofuran-2-yl)ethyl)-4-(trifluoromethyl)imidazolidin-2-one (Int C1)

To a solution of (4S)-1-(1-(6-nitrobenzofuran-2-yl)ethyl)-4-(trifluoromethyl)imidazolidin-2-one (0.32 g, 0.932 mmol) in i-PrOH (5 mL) was added Pd/C (0.1 g, 0.932 mmol) at room temperature. The mixture was heated to 50° C. and stirred and hydrogenated for 2 hrs under H₂ (15 Psi) atmosphere. The reaction mixture was filtered, and the filtrate was concentrated in vacuum. (4S)-1-(1-(6-amino-2,3-dihydrobenzofuran-2-yl)ethyl)-4-(trifluoromethyl)imidazolidin-2-one (282 mg) was obtained. ¹H NMR (400 MHz, CDCl₃) δ ppm 7.02-6.84 (m, 1H), 6.79-6.12 (m, 2H), 5.10-4.92 (m, 1H), 4.91-4.72 (m, 1H), 4.20-4.09 (m, 1H), 4.06-3.90 (m, 1H), 3.83-3.66 (m, 1H), 3.65-3.49 (m, 2H), 3.48-2.80 (m, 1H), 1.58-1.12 (m, 3H). MS (ESI, m/e) [M+H]⁺ 316.1.

Example 32: N-((1S)-cyclohexyl(6-((R)-4-ethyl-2-oxoimidazolidin-1-yl)-6-(methylcarbamoyl)-1,5,6,7-tetrahydroindeno[5,6-d]imidazol-2-yl)methyl)-4-methyl-1,2,5-oxadiazole-3-carboxamide

Step 1: 2-amino-N-methyl-5,6-dinitro-2,3-dihydro-1H-indene-2-carboxamide

To the mixture of H₂SO₄ (100 mL) and HNO₃ (25 mL) was slowly added 2-amino-N-methyl-2,3-dihydro-1H-indene-2-carboxamide (19 g, 100 mmol, dissolved in 10 mL HOAc) in batches at 0° C. After addition, the mixture was stirred for 4 hrs at room temperature. The reaction mixture was poured into saturated NaHCO₃ (aq, 500 mL) at 0˜10° C. carefully and then extracted with DCM (500 mL). The organic layer was separated and was purified by column chromatogram silica gel (eluent: DCM to DCM/MeOH (v/v)=20/1) to afford the title compound (16.81 g, yield: 60.0%).

Step 2: tert-butyl (2-(methylcarbamoyl)-5,6-dinitro-2,3-dihydro-1H-inden-2-yl)carbamate

The mixture of 2-amino-N-methyl-5,6-dinitro-2,3-dihydro-1H-indene-2-carboxamide (16.81 g, 60 mmol) and Boc₂O (26.16 g) in DCM (200 mL) was stirred overnight at room temperature. The reaction mixture was diluted with PE (200 mL), washed with brine (500 mL), dried over Na₂SO₄, and concentrated in vacuum. The crude product was purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=50/1 to 20/1) to afford the tittle product (19.76 g, yield: 86.7%). MS (ESI, m/e) [M+1]⁺ 381.3.

Step 3: tert-butyl (5,6-diamino-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-2-yl)carbamate

To the mixture of tert-butyl (2-(methylcarbamoyl)-5,6-dinitro-2,3-dihydro-1H-inden-2-yl)carbamate (19.76 g, 52 mmol) and Pd/C (1.5 g) in MeOH (500 mL) was bubbled with H₂ balloon and stirred overnight under H₂ atmosphere. The reaction mixture was filtered and the filtrate was concentrated in vacuum, then purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=50/1 to 20/1) to afford the tittle compound (14.7 g, yield: 88.46%). MS (ESI, m/e) [M+1]⁺ 321.3.

Step 4: benzyl ((1S)-2-((6-amino-2-((tert-butoxycarbonyl)amino)-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)carbamate

The mixture of (S)-2-(((benzyloxy)carbonyl)amino)-2-cyclohexylacetic acid (13.4 g, 46 mmol), tert-butyl (5,6-diamino-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-2-yl)carbamate (14.70 g, 46 mmol), HATU (19 g, 50 mmol) and TEA (10 g, 100 mmol) in DCM (500 mL) was stirred overnight at room temperature. The reaction mixture was quenched with NaHCO₃ (aq, 500 mL). The organic layer was separated, washed with brine (500 mL), dried over Na₂SO₄, and concentrated in vacuum. The crude product was purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=50/1 to 20/1) to afford the tittle compound (9.0 g, yield: 32.95%). MS (ESI, m/e) [M+1]⁺ 594.3.

Step 5: benzyl ((1S)-(6-((tert-butoxycarbonyl)amino)-6-(methylcarbamoyl)-1,5,6,7-tetrahydroindeno[5,6-d]imidazol-2-yl)(cyclohexyl)methyl)carbamate

The mixture of benzyl ((1S)-2-((6-amino-2-((tert-butoxycarbonyl)amino)-2-(methylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)carbamate (9.0 g) and AcOH (50 mL) was heated to 100° C. and stirred overnight. The reaction mixture was concentrated in vacuum, the residue was diluted with NaHCO₃ (aq, 250 mL), and extracted with DCM (250 mL), washed with brine (500 mL), dried over Na₂SO₄, and concentrated in vacuum. The crude product was purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=50/1 to 20/1) to afford the tittle compound (1.63 g, yield: 39.36%). MS (ESI, m/e) [M+1]⁺ 576.3.

Step 6: benzyl ((1S)-(6-amino-6-(methylcarbamoyl)-1,5,6,7-tetrahydroindeno[5,6-d]imidazol-2-yl)(cyclohexyl)methyl)carbamate

To a solution of benzyl ((1S)-(6-((tert-butoxycarbonyl)amino)-6-(methylcarbamoyl)-1,5,6,7-tetrahydroindeno[5,6-d]imidazol-2-yl)(cyclohexyl)methyl)carbamate (5.0 g, 8.69 mmol) in DCM (100 mL) was added HCl acid (4M, in Dioxane, 100 mL). The mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure to remove solvent. The residue was diluted with NaHCO₃ (aq, 250 mL), and extracted with DCM (250 mL). The organic layer was washed with brine (200 mL), dried over Na₂SO₄, and concentrated in vacuum. The crude product was purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=50/1 to 20/1) to afford the tittle compound (1.63 g, yield: 39.36%). MS (ESI, m/e) [M+1]⁺ 476.2.

Step 7: benzyl ((1S)-(6-(((R)-2-((tert-butoxycarbonyl)amino)butyl)amino)-6-(methylcarbamoyl)-1,5,6,7-tetrahydroindeno[5,6-d]imidazol-2-yl)(cyclohexyl)methyl)carbamate

The mixture of benzyl ((1S)-(6-amino-6-(methylcarbamoyl)-1,5,6,7-tetrahydroindeno[5,6-d]imidazol-2-yl)(cyclohexyl)methyl)carbamate (300 mg, 0.63 mmol), tert-butyl (R)-(3-methyl-1-oxobutan-2-yl)carbamate (252 mg, 1.26 mmol) and NaBH(OAc)₃ (267 mg, 1.26 mmol) in DCM (50 mL) was stirred for 2 hrs at room temperature. The reaction mixture was quenched with NaHCO₃ (aq, 100 mL), and extracted with DCM (50 mL). The organic layer was dried over Na₂SO₄ and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=50/1). Benzyl ((1S)-(6-(((R)-2-((tert-butoxycarbonyl)amino)butyl)amino)-6-(methylcarbamoyl)-1,5,6,7-tetrahydroindeno[5,6-d]imidazol-2-yl)(cyclohexyl)methyl)carbamate (310 mg, yield: 71.4%) was obtained. MS (ESI, m/e) [M+1]⁺ 647.4.

Step 8: benzyl ((1S)-(6-(((R)-2-aminobutyl)amino)-6-(methylcarbamoyl)-1,5,6,7-tetrahydroindeno[5,6-d]imidazol-2-yl)(cyclohexyl)methyl)carbamate

The mixture of benzyl ((1S)-(6-(((R)-2-((tert-butoxycarbonyl)amino)butyl)amino)-6-(methylcarbamoyl)-1,5,6,7-tetrahydroindeno[5,6-d]imidazol-2-yl)(cyclohexyl)methyl)carbamate (310 mg, 0.45 mmol) and TFA (2 mL) in DCM (5 mL) was stirred for 2 hrs. The mixture was concentrated in vacuo to afford benzyl ((1S)-(6-(((R)-2-aminobutyl)amino)-6-(methylcarbamoyl)-1,5,6,7-tetrahydroindeno[5,6-d]imidazol-2-yl)(cyclohexyl)methyl)carbamate (236 mg, crude), which was used directly in next step. MS (ESI, m/e) [M+1]⁺ 547.3.

Step 9: benzyl ((1S)-cyclohexyl(6-((R)-4-ethyl-2-oxoimidazolidin-1-yl)-6-(methylcarbamoyl)-1,5,6,7-tetrahydroindeno[5,6-d]imidazol-2-yl)methyl)carbamate

The mixture of benzyl ((1S)-(6-(((R)-2-aminobutyl)amino)-6-(methylcarbamoyl)-1,5,6,7-tetrahydroindeno[5,6-d]imidazol-2-yl)(cyclohexyl)methyl)carbamate (236 mg, 0.44 mmol), TEA (0.5 mL) and CDI (142 mg, 0.88 mmol) in THF (20 mL) was heated to 60° C. and stirred for 2 hrs. The reaction mixture was quenched with brine (50 mL), extracted with EA (50×2 mL). Combined layers were dried over Na₂SO₄ and concentrated in vacuum. The crude product was purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=50/1 to 20/1). Benzyl ((1S)-cyclohexyl(6-((R)-4-ethyl-2-oxoimidazolidin-1-yl)-6-(methylcarbamoyl)-1,5,6,7-tetrahydroindeno[5,6-d]imidazol-2-yl)methyl)carbamate was obtained (236 mg, yield: 93.18%). MS (ESI, m/e) [M+1]⁺ 573.3.

Step 10: 2-((S)-amino(cyclohexyl)methyl)-6-((R)-4-ethyl-2-oxoimidazolidin-1-yl)-N-methyl-1,5,6,7-tetrahydroindeno[5,6-d]imidazole-6-carboxamide

To the mixture of was benzyl ((1S)-cyclohexyl(6-((R)-4-ethyl-2-oxoimidazolidin-1-yl)-6-(methylcarbamoyl)-1,5,6,7-tetrahydroindeno[5,6-d]imidazol-2-yl)methyl)carbamate (236 mg, 0.41 mmol), and Pd/C (20 mg) in MeOH (50 mL) was bubbled with H₂ balloon and stirred overnight at H₂ atmosphere for deprotection. The reaction mixture was then filtrated, and the filtrate was concentrated in vacuum. The crude product was purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=50/1 to 20/1) to afford the tittle amine compound (142 mg, yield: 55.66%). MS (ESI, m/e) [M+1]⁺ 439.3.

Step 11: N-((1S)-cyclohexyl(6-((R)-4-ethyl-2-oxoimidazolidin-1-yl)-6-(methylcarbamoyl)-1,5,6,7-tetrahydroindeno[5,6-d]imidazol-2-yl)methyl)-4-methyl-1,2,5-oxadiazole-3-carboxamide

Example 32

To a solution of 2-((S)-amino(cyclohexyl)methyl)-6-((R)-4-ethyl-2-oxoimidazolidin-1-yl)-N-methyl-1,5,6,7-tetrahydroindeno[5,6-d]imidazole-6-carboxamide (22 mg, 0.05 mmol) in DCM (10 mL) were added 4-methyl-1,2,5-oxadiazole-3-carboxylic acid (7 mg, 0.05 mmol), HATU (19 mg, 0.05 mmol) and TEA (10 mg, 0.1 mmol). The mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched with aq. NaHCO₃ (50 mL) and diluted with DCM (20 mL). The organic layers were dried over Na₂SO₄, filtered and concentrated in vacuum. The crude product was purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=50/1 to 20/1). The tittle compound was obtained (13 mg, yield: 47.4%). ¹H NMR (400 MHz, DMSO-d₆) δ ppm: 12.20 (br, 1H), 9.42 (d, J=8.8 Hz, 1H), 7.55-7.25 (m, 3H), 6.69 (s, 1H), 5.05 (t, J=8.4 Hz, 1H), 3.65-3.40 (m, 4H), 3.32-3.23 (m, 2H), 2.93-2.87 (m, 1H), 2.58 (d, J=4.4 Hz, 3H), 2.10-1.55 (m, 5H), 1.42-1.27 (m, 3H), 1.21-0.95 (m, 5H), 0.71 (t, J=7.2 Hz, 3H). MS (ESI, m/e) [M+1]⁺ 549.4.

Example 145: N-((1S)-1-cyclohexyl-2-((6-(methylcarbamoyl)-6-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide

Step 1: 9,12-dioxa-1,3-diazadispiro[4.2.4⁸.2⁵]tetradecane-2,4-dione

A mixture of 1,4-dioxaspiro[4.5]decan-8-one (9.55 g, 61.2 mmol), NaCN (3 g, 61.2 mmol) and (NH₄)₂CO₃ (23.5 g, 244.8 mmol) in H₂O (100 mL) and EtOH (5 mL) was stirred at 60° C. overnight. The reaction mixture was cooled to room temperature and stayed 1 day. The precipitate was filtered and then the cake was dried in air to obtain 9,12-dioxa-1,3-diazadispiro[4.2.4⁸.2⁵]tetradecane-2,4-dione (7.38 g, crude). H NMR (400 MHz, DMSO-d₆) δ ppm: 10.59 (s, 1H), 8.44 (s, 1H), 3.87 (s, 4H), 1.95-1.78 (m, 2H), 1.73-1.69 (m, 4H), 1.59-1.56 (m, 2H).

Step 2: 8-amino-1,4-dioxaspiro[4.5]decane-8-carboxylic acid

A solution of 9,12-dioxa-1,3-diazadispiro[4.2.4⁸.2⁵]tetradecane-2,4-dione (2 g) in NaOH solution (6 N, 15 mL) was stirred at 140° C. in a sealed tube for 3 hrs. The reaction mixture was cooled to room temperature and acidified to pH=4 with 6N HCl acid. After the mixture was concentrated in vacuum to remove solvent, the residue was dissolved with DCM/MeOH=10/1 (80 mL) and stirred for 10 min. The mixture was filtered and the filtrate was concentrated to obtain 8-amino-1,4-dioxaspiro[4.5]decane-8-carboxylic acid (1.13 g, crude). MS (ESI) m/e [M+1]⁺ 202.1

Step 3: 8-(((benzyloxy)carbonyl)amino)-1,4-dioxaspiro[4.5]decane-8-carboxylic acid

A mixture of 8-amino-1,4-dioxaspiro[4.5]decane-8-carboxylic acid (1.13 g), CbzCl (966 mg) and Et₃N (1.15 g, 3.06 mmol) in THF (30 mL) and H₂O (30 mL) was stirred at room temperature for 3 hrs. The reaction mixture was diluted with MTBE (30 mL) and stirred for 10 min. The water phase was collected and concentrated in vacuum. The resulted sloid was dried in air to obtain 8-(((benzyloxy)carbonyl)amino)-1,4-dioxaspiro[4.5]decane-8-carboxylic acid (1.86 g, crude). MS (ESI) m/e [M+1]⁺ 337.1.

Step 4: benzyl (8-(methylcarbamoyl)-1,4-dioxaspiro[4.5]decan-8-yl)carbamate

A mixture of 8-(((benzyloxy)carbonyl)amino)-1,4-dioxaspiro[4.5]decane-8-carboxylic acid (1.86 g), methylamine hydrochloride (385 mg, 5.7 mmol), HATU (2.17 g, 5.7 mmol) and Et₃N (1.15 g, 11.4 mmol) in DCM (60 mL) was stirred at room temperature overnight. The reaction mixture was concentrated and the residue was then purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=50/1). benzyl (8-(methylcarbamoyl)-1,4-dioxaspiro[4.5]decan-8-yl)carbamate (1.77 g) was obtained. MS (ESI) m/e [M+1]⁺ 349.2.

Step 5: benzyl (1-(methylcarbamoyl)-4-oxocyclohexyl)carbamate

A solution of benzyl (8-(methylcarbamoyl)-1,4-dioxaspiro[4.5]decan-8-yl)carbamate (1.77 g, 5.7 mmol) in TFA (10 mL) was stirred at room temperature for 3 hrs. The reaction mixture was concentrated to remove TFA. The residue was neutralized with aq. NaHCO₃ and was then extracted with DCM (50 mL×3). The organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. Benzyl (1-(methylcarbamoyl)-4-oxocyclohexyl)carbamate (615 mg, crude) was obtained. MS (ESI) m/e [M+1]⁺ 305.1

Step 6: tert-butyl 2-amino-6-(((benzyloxy)carbonyl)amino)-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate

A mixture of benzyl (1-(methylcarbamoyl)-4-oxocyclohexyl)carbamate (615 mg, 2.02 mmol), tert-butyl 2-cyanoacetate (500 mg, 2.02 mmol), sulfur (65 mg, 2.02 mmol) and morpholine (176 mg, 2.02 mmol) in EtOH (25 mL) was stirred at 80° C. overnight. The mixture was cooled to room temperature and concentrated in vacuum. The residue was purified by pre-TLC (eluent: EA/PE (v/v)=1/1). Tert-butyl 2-amino-6-(((benzyloxy)carbonyl)amino)-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (287 mg) was obtained. MS (ESI) m/e [M+1]⁺ 460.3.

Step 7: benzyl (2-amino-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)carbamate

To a solution of tert-butyl 2-amino-6-(((benzyloxy)carbonyl)amino)-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (287 mg, 0.625 mmol) in THF (30 mL) were added HCl acid (6 N, 10 mL). The mixture was stirred at 60° C. for 4 hrs. After cooled to room temperature, the reaction mixture was neutralized with aq. NaHCO₃ and was then extracted with DCM (50 mL×3). The organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The residue was purified by pre-TLC (eluent: MeOH/DCM (v/v)=1/10) to obtain benzyl (2-amino-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)carbamate (237 mg). MS (ESI) m/e [M+1]+360.2.

Step 8: benzyl (2-((S)-2-((tert-butoxycarbonyl)amino)-2-cyclohexylacetamido)-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)carbamate

To a solution of benzyl (2-amino-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)carbamate (237 mg, 0.625 mmol) in DCM (15 mL) were added (S)-2-((tert-butoxycarbonyl)amino)-2-cyclohexylacetic acid (161 mg, 0.625 mmol), HATU (238 mg, 0.625 mmol) and Et₃N (189 mg, 1.875 mmol). The mixture was stirred at room temperature overnight. The reaction mixture was concentrated, and the residue was purified by pre-TLC (MeOH/DCM=1/10). Benzyl (2-((S)-2-((tert-butoxycarbonyl)amino)-2-cyclohexylacetamido)-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)carbamate (223 mg) was obtained. MS (ESI) m/e [M+1]⁺ 599.3.

Step 9: benzyl (2-((S)-2-amino-2-cyclohexylacetamido)-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)carbamate

A solution of benzyl (2-((S)-2-((tert-butoxycarbonyl)amino)-2-cyclohexylacetamido)-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)carbamate (223 mg, 0.372 mmol) in TFA (5 mL) was stirred at room temperature for 1 hr. The reaction was concentrated in vacuum to give the crude title compound (300 mg). MS (ESI) m/e [M+1]⁺ 499.4.

Step 10: benzyl (2-((S)-2-cyclohexyl-2-(1-methyl-1H-pyrazole-5-carboxamido)acetamido)-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)carbamate

To a solution of benzyl (2-((S)-2-amino-2-cyclohexylacetamido)-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)carbamate (300 mg) in DCM (15 mL), were added 1-methyl-1H-pyrazole-5-carboxylic acid (47 mg, 0.372 mmol), HATU (141 mg, 0.372 mmol) and Et₃N (190 mg, 1.86 mmol). The mixture was stirred at room temperature for 48 hrs. The reaction mixture was concentrated in vacuum. The residue was purified by pre-TLC (eluent: MeOH/DCM (v/v)=1/10) to obtain benzyl (2—((S)-2-cyclohexyl-2-(1-methyl-1H-pyrazole-5-carboxamido)acetamido)-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)carbamate (90 mg). MS (ESI) m/e [M+1]⁺ 607.4.

Step 11: N-((1S)-2-((6-amino-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-1-cyclohexyl-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide

To a solution of benzyl (2-((S)-2-cyclohexyl-2-(1-methyl-1H-pyrazole-5-carboxamido)acetamido)-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)carbamate (80 mg, 0.13 mmol) in DCM (10 mL) was added TMSI (1 mL, 1 mol/L). The mixture was stirred at room temperature for 30 min. The reaction mixture was neutralized with aq. NaHCO₃ and extracted with DCM (50 mL×3). The organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. N-((1S)-2-((6-amino-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-1-cyclohexyl-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide (63 mg, crude) was obtained. MS (ESI) m/e [M+1]⁺ 473.2.

Step 12: tert-butyl ((1-(((2-((S)-2-cyclohexyl-2-(1-methyl-1H-pyrazole-5-carboxamido)acetamido)-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)amino)methyl)cyclopropyl)methyl)carbamate

A mixture of N-((1S)-2-((6-amino-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-1-cyclohexyl-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide (30 mg, 0.063 mmol), tert-butyl ((1-formylcyclopropyl)methyl)carbamate (13 mg, 0.063 mmol) and NaBH(OAc)₃ (14 mg, 0.063 mmol) in DCM (10 mL) was stirred at room temperature overnight. The reaction mixture was concentrated in vacuum. The residue was purified by pre-TLC (eluent: MeOH/DCM (v/v)=1/15) to obtain the desired product (10 mg). MS (ESI) m/e [M+1]⁺ 656.5.

Step 13: N-((1S)-2-((6-(((1-(aminomethyl)cyclopropyl)methyl)amino)-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-1-cyclohexyl-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide

A mixture of tert-butyl ((1-(((2-((S)-2-cyclohexyl-2-(1-methyl-1H-pyrazole-5-carboxamido)acetamido)-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)amino)methyl)cyclopropyl)methyl)carbamate (10 mg) in TFA (2 mL) was stirred at room temperature for 30 min. The reaction was concentrated to give the desired product as a white solid (10 mg). MS (ESI) m/e [M+1]⁺ 556.4.

Step 14: N-((1S)-1-cyclohexyl-2-((6-(methylcarbamoyl)-6-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide

Example 145

To a solution of N-((1S)-2-((6-(((1-(aminomethyl)cyclopropyl)methyl)amino)-6-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-1-cyclohexyl-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide (10 mg) and Et₃N (30 mg) in DMF (2 mL), was added CDI (3 mg). The mixture was stirred at 60° C. for 2 hrs. The reaction mixture was concentrated in vacuum and the residue was purified by pre-TLC (eluent: MeOH/DCM (v/v)=1/15). The title compound example 145 was obtained (2 mg). MS (ESI) m/e [M+1]⁺ 582.2.

Example 170: N-((1S)-1-cyclohexyl-2-((2-isopropyl-2-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-2,3-dihydro-1H-inden-5-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide

Step 1: methyl 6-bromo-2-isopropyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate

To a solution of methyl 6-bromo-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (27 g) in dry DMF (250 ml) was added sodium hydride (8 g of a 60% suspension in oil, 200 mmol) in portions over 20 minutes under N₂ protection. The mixture was stirred for 45 minutes. 2-iodopropane (34 g, 200 mmol) was added dropwise over 15 minutes and the mixture was then stirred for 18 hrs at room temperature. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between EA (150 mL) and HCl acid (2N, 50 mL). The organic layer was separated, dried and concentrated in vacuum. The crude product was purified by column chromatography on silica gel (eluent: PE/EA (v/v)=10/1). Methyl 6-bromo-2-isopropyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (10 g, yield: 33%) was obtained. MS (ESI, m/e) [M+1]⁺ 311.0/313.0.

Step 2: methyl 6-((diphenylmethylene)amino)-2-isopropyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate

A mixture of Methyl 6-bromo-2-isopropyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (3.11 g, 10 mmol), diphenylmethanimine (2.7 g, 15 mmol), BINAP (1.87 g, 0.3 mmol), Pd₂(dba)₃ (1.4 g, 0.15 mmol) and Cs₂CO₃ (10 g, 30 mmol) in toluene (50 ml) was degassed with N₂. The mixture was heated to 100° C. and stirred for 12 hrs under N₂ atmosphere. The reaction mixture was cooled to room temperature and washed with H₂O, brine. The organic layer was dried over MgSO₄, filtered and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: hexane/EtOAc (v/v)=10/1). Methyl 6-((diphenylmethylene)amino)-2-isopropyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2.2 g, yield: 53.5%) was obtained. MS (ESI, m/e) [M+1]⁺ 412.1

Step 3: methyl 6-amino-2-isopropyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate

methyl 6-((diphenylmethylene)amino)-2-isopropyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2.2 g) was dissolved into HCl acid (1N, 15 mL) and stirred for lhour. The reaction mixture was basified with aq. NaHCO₃ to pH=8-9 and extracted with EtOAc (30 mL×3). The combined organic layers were washed with H₂O, brine, dried over MgSO₄, filtered and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: hexane/EtOAc (v/v)=1/1). Methyl 6-amino-2-isopropyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (1 g, yield: 76.9%) was obtained. MS (ESI, m/e) [M+1]⁺ 248.1.

Step 4: methyl 6-amino-1-hydroxy-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate

A solution of methyl 6-amino-2-isopropyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (1 g, 4 mmol) in MeOH (50 mL) was added NaBH₄ (154 mg, 12 mmol) in portions at 0° C. The reaction mixture was stirred for 1 hour and was then concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic layer was dried over MgSO₄ and concentrated in vacuum. Methyl 6-amino-1-hydroxy-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate (1 g, crude) was obtained. MS (ESI, m/e) [M+1]⁺ 250.1.

Step 5: methyl 5-amino-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate

To a solution of methyl 6-amino-1-hydroxy-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate (249 mg, 1 mmol) in TFA (10 mL) was added triethyl silane (2 mL). The mixture was stirred at room temperature for 1 hour. After the reaction mixture was concentrated to remove TFA, the residue was dissolved in DCM (25 mL) and washed with sat·aq·NaHCO₃. The organic layer was dried over MgSO₄ and concentrated in vacuum. Methyl 5-amino-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate (240 mg, crude) was obtained. MS (ESI, m/e) [M+1]⁺ 234.1.

Step 6: methyl 5-((S)-2-((tert-butoxycarbonyl)amino)-2-cyclohexylacetamido)-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate

To a solution of methyl 5-amino-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate (466 mg, 2 mmol) in DCM (25 mL) were added (S)-2-((tert-butoxycarbonyl)amino)-2-cyclohexylacetic acid (819 mg, 3 mmol), HATU (1.35 g, 3.6 mmol) and TEA (1 mL). The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated to remove solvent and the residue was purified by prep-TLC (eluent: DCM/MeOH (v/v)=15:1). methyl 5-((S)-2-((tert-butoxycarbonyl)amino)-2-cyclohexylacetamido)-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate (623 mg, yield: 56%) was obtained. MS (ESI, m/e) [M+1]⁺ 473.3.

Step 7: methyl 5-((S)-2-amino-2-cyclohexylacetamido)-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate

Methyl 5-((S)-2-((tert-butoxycarbonyl)amino)-2-cyclohexylacetamido)-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate (623 mg, 1.32 mmol) was dissolved into HCl solution (10 mL, 2M in dioxane) and stirred at room temperature for 1 hour. After the reaction mixture was concentrated to remove solvent in vacuum, methyl 5-((S)-2-amino-2-cyclohexylacetamido)-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate salts of HCl (491 mg, crude) was obtained. MS (ESI, m/e) [M+1]⁺ 373.1.

Step 8: methyl 5-((S)-2-cyclohexyl-2-(1-methyl-1H-pyrazole-5-carboxamido)acetamido)-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate

To a solution of methyl 5-((S)-2-amino-2-cyclohexylacetamido)-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate (491 mg, crude) and TEA (1.0 mL) in DCM (25 mL) were added 1-methyl-1H-pyrazole-5-carboxylic acid (200 mg, 1.58 mmol) and HATU (752 mg, 1.98 mmol). The mixture was stirred at room temperature for 2 hrs. The reaction mixture was quenched with aq. NaHCO₃ (50 mL) and diluted with DCM (20 mL). The organic layers were dried over Na₂SO₄ and concentrated in vacuum. The residue was purified by prep-TLC (eluent: DCM/MeOH (v/v)=15:1). Methyl 5-((S)-2-cyclohexyl-2-(1-methyl-1H-pyrazole-5-carboxamido)acetamido)-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate (200 mg, yield: 32%) was obtained. MS (ESI, m/e) [M+1]⁺ 481.1.

Step 9: 5-((S)-2-cyclohexyl-2-(1-methyl-1H-pyrazole-5-carboxamido)acetamido)-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylic acid

To a solution of methyl 5-((S)-2-cyclohexyl-2-(1-methyl-1H-pyrazole-5-carboxamido)acetamido)-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate (200 mg, 0.42 mmol) in methanol (5 mL), was added aq. NaOH (2 mL, 1.0 N). The mixture was stirred overnight at room temperature. The reaction mixture was acidified to pH=5-6 with diluted HCl acid and extracted with EtOAc (15 mL×3). The organic layers were washed with H₂O, brine, dried over MgSO₄, filtered and concentrated in vacuum. 5-((S)-2-cyclohexyl-2-(1-methyl-1H-pyrazole-5-carboxamido)acetamido)-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylic acid (100 mg, crude) was obtained. MS (ESI, m/e) [M+1]+467.0.

Step 10: N-((1S)-2-((2-amino-2-isopropyl-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide

To a solution of 5-((S)-2-cyclohexyl-2-(1-methyl-1H-pyrazole-5-carboxamido)acetamido)-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylic acid (60 mg, 0.13 mmol) in toluene (5 mL) was added DPPA (53 mg) and TEA (0.1 mL). The mixture was heated to 90° C. and stirred for 1 hour. The reaction mixture was cooled and concentrated to remove solvent. The residue was dissolved into HCl acid (5 mL, 1N) and then stirred for 1 hour. The mixture was basified with aq. NaHCO₃ to pH ˜9 and was extracted with EtOAc (10 mL×3). The organic layer was washed with H₂O, brine, dried over MgSO₄, filtered and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: hexane/EtOAc (v/v)=1/1). N-((1S)-2-((2-amino-2-isopropyl-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide (30 mg, yield: 54%) was obtained. MS (ESI, m/e) [M+1]⁺ 438.1.

Step 11: tert-butyl ((1-(((5-((S)-2-cyclohexyl-2-(1-methyl-1H-pyrazole-5-carboxamido)acetamido)-2-isopropyl-2,3-dihydro-1H-inden-2-yl)amino)methyl)cyclopropyl)methyl)carbamate

A mixture of N-((1S)-2-((2-amino-2-isopropyl-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide (30 mg, 0.069 mmol), tert-butyl ((1-formylcyclopropyl)methyl)carbamate (14 mg, 0.069 mmol) and NaBH(OAc)₃ (50 mg) in DCM (5 mL) was stirred at room temperature for 1 hour. The reaction mixture was diluted with DCM (15 mL) and then washed with H₂O, brine. The organic layer was separated and dried over MgSO₄, filtered and concentrated in vacuum. The residue was purified by prep-TLC (eluent: DCM/MeOH (v/v)=15:1). Tert-butyl ((1-(((5-((S)-2-cyclohexyl-2-(1-methyl-1H-pyrazole-5-carboxamido)acetamido)-2-isopropyl-2,3-dihydro-1H-inden-2-yl)amino)methyl)cyclopropyl)methyl)carbamate (20 mg, yield: 47%) was obtained. MS (ESI, m/e) [M+1]⁺ 621.1.

Step 12: N-((1S)-2-((2-(((1-(aminomethyl)cyclopropyl)methyl)amino)-2-isopropyl-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide

Tert-butyl ((1-(((5-((S)-2-cyclohexyl-2-(1-methyl-1H-pyrazole-5-carboxamido)acetamido)-2-isopropyl-2,3-dihydro-1H-inden-2-yl)amino)methyl)cyclopropyl)methyl)carbamate (20 mg) was dissolved into HCl solution (10 mL, 2M in dioxane) and stirred at room temperature for 1 hour. The reaction mixture was concentrated in vacuum, N-((1S)-2-((2-(((1-(aminomethyl)cyclopropyl)methyl)amino)-2-isopropyl-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide salts of HCl (20 mg crude) was obtained. MS (ESI, m/e) [M+1]⁺ 521.3.

Step 13: N-((1S)-1-cyclohexyl-2-((2-isopropyl-2-(6-oxo-5,7-diazaspiro[2.5]octan-5-yl)-2,3-dihydro-1H-inden-5-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide (Example 170)

To a solution of methyl N-((1S)-2-((2-(((1-(aminomethyl)cyclopropyl)methyl)amino)-2-isopropyl-2,3-dihydro-1H-inden-5-yl)amino)-1-cyclohexyl-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide (20 mg) and TEA (0.5 mL) in THF (5 mL) was added CDI (20 mg). The mixture was heated to reflux and stirred for 3 hrs. The reaction mixture was cooled to room temperature and concentrated in vacuum. The residue was purified by prep-TLC (eluent: DCM/MeOH (v/v)=15:1). The title compound (10 mg, yield: 28.6% for 2 steps) was obtained. ¹H NMR (400 MHz, DMSO-d₆) δ ppm: 10.05 (s, 1H), 8.45 (d, J=8.0 Hz, 1H), 7.45 (t, J=8.6 Hz, 2H), 7.29 (s, 1H), 7.04 (d, J=10.4 Hz, 2H), 6.05 (s, 1H), 4.44-4.31 (m, 1H), 4.03 (s, 3H), 3.21-2.92 (m, 4H), 2.86 (s, 2H), 2.67 (s, 2H), 1.94-1.49 (m, 8H), 128-1.15 (m, 4H), 0.70 (d, J=6.6 Hz, 6H), 0.52-0.38 (m, 4H). MS (ESI, m/e) [M+1]⁺ 547.7.

Example 212: N-((2S)-1,1-dicyclopropyl-3-((2-isopropyl-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)-4-methyl-1,2,5-oxadiazole-3-carboxamide

Step 1: methyl 2-isopropyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate

To a solution of methyl 1-oxo-2,3-dihydro-1H-indene-2-carboxylate (14 g, 73.6 mmol) in dry DMF (250 ml) was added sodium hydride (8.8 g of a 60% suspension in oil, 222 mmol) in portions over 20 minutes at 0° C. After the mixture was further stirred for 45 minutes, 2-iodopropane (25 g, 148 mmol) was added dropwise over 15 minutes. The mixture was then heated to 90° C. and and stirred for 18 hrs. The reaction mixture was cooled to r.t and then poured into ice/water (100 mL), extracted with EA (100 mL×3). The combined organic layers were dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: PE/EA (v/v)=10/1). Methyl 2-isopropyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (8 g, 50%) was obtained. MS (ESI, m/e) [M+1]⁺ 233.1.

Step 2: methyl 1-hydroxy-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate

To a solution of methyl 2-isopropyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (1.8 g, 7.8 mmol) in MeOH (50 mL) was added NaBH₄ (1.2 g, 32 mmol) in portions at 0° C. The mixture was stirred for 1 hour and then was concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic layer was dried over MgSO₄, filtered and concentrated in vacuum. Methyl 1-hydroxy-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate (1.8 g, crude) was obtained, which was used directly in next step. MS (ESI, m/e) [M−17]⁺ 217.1.

Step 3: methyl 2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate

To a solution of methyl 1-hydroxy-2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate (1.7 g, 7.2 mmol) in TFA (25 mL) was added triethyl silane (5 mL). The mixture was stirred at room temperature for 1 hour. The reaction mixture was then concentrated under reduced pressure to remove solvent. The residue was dissolved in DCM (25 mL) and washed with sat·aq·NaHCO₃ (10 mL). The organic layer was washed with brine, dried over MgSO₄ and concentrated in vacuum. Methyl 2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate (1.5 g, crude) was obtained, which was used directly in next step. MS (ESI, m/e) [M+1]⁺ 219.1.

Step 4: 2-isopropyl-2,3-dihydro-1H-indene-2-carboxylic acid

To a solution of methyl 2-isopropyl-2,3-dihydro-1H-indene-2-carboxylate (218 mg, 1 mmol) in methanol (3 mL) was added aq. NaOH (1.0 N, 2 mL, 2 mmol). The mixture was stirred overnight at room temperature. The reaction mixture was then acidified with HCl acid (2.0 N), and extracted with EtOAc (10 mL×3). The combined organic layers were washed with brine, H₂O, dried over MgSO₄, filtered and concentrated in vacuum. 2-isopropyl-2,3-dihydro-1H-indene-2-carboxylic acid (200 mg, crude) was obtained. MS (ESI, m/e) [M+1]⁺ 205.1.

Step 5: 2-isopropyl-2,3-dihydro-1H-inden-2-amine

To a solution of 2-isopropyl-2,3-dihydro-1H-indene-2-carboxylic acid (1.2 g, 6.8 mmol) in toluene (25 mL) was added DPPA (2.75 g) and TEA (3 mL). The mixture was heated to 90° C. and stirred for 1 hour. The reaction mixture was concentrated under reduced pressure. The residue was diluted into HCl acid (1N, 15 mL) and then stirred for 1 hour. The mixture was basified with aq. NaHCO₃ to pH ˜8-9 and extracted with EtOAc (10 mL×3). The combined organic layers were washed with H₂O, brine, dried over MgSO₄, filtered and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: hexane/EtOAc (v/v)=4/1). 2-isopropyl-2,3-dihydro-1H-inden-2-amine (700 mg, yield: 69%) was obtained. MS (ESI, m/e) [M+1]⁺ 176.1

Step 6: tert-butyl (1,1,1-trifluoro-3-((2-isopropyl-2,3-dihydro-1H-inden-2-yl)amino)-3-oxopropan-2-yl)carbamate

To the mixture of 2-(((benzyloxy)carbonyl)amino)-3,3,3-trifluoropropanoic acid (1.17 g, 4.8 mmol), HATU (1.98 g, 5.2 mmol) in DCM (30 mL) were added 2-isopropyl-2,3-dihydro-1H-inden-2-aminen (700 mg, 4 mmol) and TEA (1.6 g, 15.4 mmol) at 0° C. The mixture was stirred for 1.5 hrs at room temperature. The reaction mixture was diluted with DCM and quenched with aq. NaHCO₃. The organic layer was washed with brine, dried and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: hexane/EtOAc (v/v)=5/1). Tert-butyl (1,1,1-trifluoro-3-((2-isopropyl-2,3-dihydro-1H-inden-2-yl)amino)-3-oxopropan-2-yl)carbamate (750 mg, yield: 46%) was obtained. MS (ESI, m/e) [M+1]⁺ 401.1.

Step 7: tert-butyl (1,1,1-trifluoro-3-((2-isopropyl-2,3-dihydro-1H-inden-2-yl)amino)propan-2-yl)carbamate

To a solution of tert-butyl (1,1,1-trifluoro-3-((2-isopropyl-2,3-dihydro-1H-inden-2-yl)amino)-3-oxopropan-2-yl)carbamate (750 mg, 1.8 mmol) in THF (10 mL) was added BH₃-Me₂S (10 mL) dropwise. The mixture was heated to 70° C. and stirred for 4 hrs. The reaction mixture was quenched with MeOH (10 mL). After solvent was removed, the residue was purified by column chromatography on silica gel (eluent: hexane/EtOAc (v/v)=4/1). Tert-butyl (1,1,1-trifluoro-3-((2-isopropyl-2,3-dihydro-1H-inden-2-yl)amino)propan-2-yl)carbamate (500 mg, 72%) was obtained. MS (ESI, m/e) [M+1]⁺ 387.2

Step 8: 3,3,3-trifluoro-N¹-(2-isopropyl-2,3-dihydro-1H-inden-2-yl)propane-1,2-diamine

To a solution of tert-butyl (1,1,1-trifluoro-3-((2-isopropyl-2,3-dihydro-1H-inden-2-yl)amino)propan-2-yl)carbamate (500 mg) in THF was added HCl in dioxane (2M, 10 mL). The mixture was stirred at room temperature for 1 hour. After the solvent was removed in vacuum, 3,3,3-trifluoro-N¹-(2-isopropyl-2,3-dihydro-1H-inden-2-yl)propane-1,2-diamine salts (450 mg, crude) was obtained, which was used directly in next step.

Step 9: 1-(2-isopropyl-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one

To a solution of 3,3,3-trifluoro-N1-(2-isopropyl-2,3-dihydro-1H-inden-2-yl)propane-1,2-diamine (400 mg, 1.4 mmol) and TEA (1.5 mL) in THF (15 mL) was added CDI (324 mg, 2 mmol). The mixture was heated to reflux and stirred for 3 hrs. After cooled to r.t., the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/EtOAc (v/v)=5/1). 1-(2-isopropyl-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one (150 mg, 2 steps yield: 34%) was obtained. MS (ESI, m/e) [M+1]+313.0.

Step 10: 1-(2-isopropyl-5-nitro-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one

To the mixture of H₂SO₄ (2 mL) and HNO₃ (3 mL) was added a solution of 1-(2-isopropyl-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one (80 mg, 0.25 mmol) in HOAc (2 mL) in batches at 0° C. The mixture was stirred for 5 mins at 0° C. and then quenched with saturated aq. NaHCO₃ (10 mL), extracted with DCM (10 mL×3). The organic layers were washed with H₂O, brine, dried over MgSO₄, filtered, and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: hexane/EtOAc (v/v)=4/1). 1-(2-isopropyl-5-nitro-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one (40 mg, yield: 44%) was obtained. MS (ESI, m/e) [M+1]⁺ 358.0.

Step 11: 1-(5-amino-2-isopropyl-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one

To a solution of 1-(2-isopropyl-5-nitro-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one (40 mg, 0.11 mmol) in MeOH (10 mL) was added Pd/C (10 mg). The mixture was stirred under H₂ atmosphere for 1 hour. The reaction mixture was filtered and the filtrate was concentrated in vacuum. 1-(5-amino-2-isopropyl-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one (40 mg, crude) was obtained. MS (ESI, m/e) [M+1]⁺ 328.0.

Step 12: tert-butyl ((2S)-1,1-dicyclopropyl-3-((2-isopropyl-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)carbamate

To a solution of 1-(5-amino-2-isopropyl-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one (40 mg, 0.11 mmol) in DCM were added (S)-2-((tert-butoxycarbonyl)amino)-3,3-dicyclopropylpropanoic acid (30 mg, 0.11 mmol), HATU (63 mg, 0.17 mmol) and TEA (0.1 mL). The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated and purified by prep-TLC to give tert-butyl ((2S)-1,1-dicyclopropyl-3-((2-isopropyl-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)carbamate (30 mg, yield: 47%). MS (ESI, m/e) [M+1]⁺ 579.1.

Step 13: (2S)-2-amino-3,3-dicyclopropyl-N-(2-isopropyl-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)propanamide

To a solution of tert-butyl ((2S)-1,1-dicyclopropyl-3-((2-isopropyl-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)carbamate (30 mg) in THF was added HCl in dioxane (2M, 10 mL). The mixture was stirred at room temperature for 1 hour. After the solvent was removed in vacuum, (2S)-2-amino-3,3-dicyclopropyl-N-(2-isopropyl-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)propanamide (20 mg, crude) was obtained. MS (ESI, m/e) [M+1]⁺ 479.1.

Step 14: N-((2S)-1,1-dicyclopropyl-3-((2-isopropyl-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)-4-methyl-1,2,5-oxadiazole-3-carboxamide

Example 212

To a solution of (2S)-2-amino-3,3-dicyclopropyl-N-(2-isopropyl-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)propanamide (20 mg, 0.042 mmol) in DCM (10 mL) were added 4-methyl-1,2,5-oxadiazole-3-carboxylic acid (5 mg, 0.042 mmol), HATU (24 mg, 0.063 mmol) and TEA (0.1 mL). The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated to remove solvent. The residue was purified by prep-TLC (eluent: DCM/CH3OH (v/v)=20/1). The title compound example 212 (8 mg, yield: 32%) was obtained. ¹H NMR (400 MHz, DMSO-d₆) δ ppm: 10.06 (s, 1H), 9.02 (d, J=8.8 Hz, 1H), 7.46 (d, J=7.8 Hz, 1H), 7.33 (d, J=8.2 Hz, 1H), 7.22 (s, 1H), 7.12 (d, J=8.0 Hz, 1H), 4.89-4.80 (m, 1H), 4.24 (s, 1H), 3.65 (d, J=10.6 Hz, 1H), 3.49-3.41 (m, 2H), 3.09-3.01 (m, 3H), 2.59-2.53 (m, 1H), 2.48 (s, 3H), 0.94-0.76 (m, 9H), 0.50-0.11 (m, 8H). MS (ESI, m/e) [M+1]⁺ 589.5.

Example 238

N-((2S)-1,1-dicyclopropyl-3-((2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(2,2,2-trifluoro-1-hydroxyethyl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)-4-methyl-1,2,5-oxadiazole-3-carboxamide

Step 1: (R)-1-(2-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)-4-isopropylimidazolidin-2-one

To a solution of methyl (R)-2-(4-isopropyl-2-oxoimidazolidin-1-yl)-2,3-dihydro-1H-indene-2-carboxylate (430 mg, 1.4 mmol, prepared by the procedure similar with 2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-N-methyl-5-nitro-2,3-dihydro-1H-indene-2-carboxamide as described in intermediate A2) in THF (8 mL) was added a solution of LAH (2.5 M, 1.5 mL, 3.7 mmol) dropwise with stirring at 0° C. under N₂ atmosphere. After addition, the mixture was stirred for 1 hour at 0° C. The reaction mixture was quenched by aq. Na₂SO₄ and extracted with EA (15 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The residue was purified by Prep-TLC (eluent: DCM/MeOH (v/v)=20/1) to afford (R)-1-(2-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)-4-isopropylimidazolidin-2-one (270 mg, yield: 69%). MS (ESI) m/e [M+1]⁺ 275.1.

Step 2: (R)-2-(4-isopropyl-2-oxoimidazolidin-1-yl)-2,3-dihydro-1H-indene-2-carbaldehyde

To a solution of (R)-1-(2-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)-4-isopropylimidazolidin-2-one (270 mg, 1.0 mmol) in DCM (20 mL). The resulting solution was cooled to 0° C. under nitrogen atmosphere was added Dess-Martin reagent (636 mg, 1.5 mmol) in portions at 0° C. under nitrogen atmosphere. The mixture was stirred at room temperature for 2 hrs. The reaction mixture was quenched by aq. Na₂S₂O₃ (5 mL) at 0° C. and was then diluted with aq. NaHCO₃ (10 mL) and extracted with EA (15 mL×3). The combined organic layers were washed with brine, dried and concentrated in vacuum. The residue was purified by Prep-TLC (eluent: DCM/MeOH (v/v)=30/1) to afford (R)-2-(4-isopropyl-2-oxoimidazolidin-1-yl)-2,3-dihydro-1H-indene-2-carbaldehyde (240 mg, yield: 88%). MS (ESI) m/e [M+1]⁺ 273.1.

Step 3: (4R)-4-isopropyl-1-(2-(2,2,2-trifluoro-1-((trimethylsilyl)oxy)ethyl)-2,3-dihydro-1H-inden-2-yl)imidazolidin-2-one

To a solution of (R)-2-(4-isopropyl-2-oxoimidazolidin-1-yl)-2,3-dihydro-1H-indene-2-carbaldehyde (240 mg, 0.88 mmol) in THF (10 mL) was added CsF (174 mg, 1.15 mmol) under nitrogen atmosphere. The resulting mixture was cooled to 0° C. To this mixture was added TMS-CF₃ (163 mg, 1.15 mmol). The mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with EtOAc (50 mL) and then washed with brine. The organic layer was separated, dried over Na₂SO₄ and concentrated in vacuum. (4R)-4-isopropyl-1-(2-(2,2,2-trifluoro-1-((trimethylsilyl)oxy)ethyl)-2,3-dihydro-1H-inden-2-yl)imidazolidin-2-one (300 mg, crude) was obtained, which used directly in next step.

Step 4: (4R)-4-isopropyl-1-(2-(2,2,2-trifluoro-1-hydroxyethyl)-2,3-dihydro-1H-inden-2-yl)imidazolidin-2-one

(4R)-4-isopropyl-1-(2-(2,2,2-trifluoro-1-((trimethylsilyl)oxy)ethyl)-2,3-dihydro-1H-inden-2-yl)imidazolidin-2-one (300 mg, crude) was dissolved into THF (10 mL) and was cooled to 0° C. To this solution was added TBAF (0.1 mL, 1M). The mixture was stirred at 0° C. for 1 hour. The reaction mixture was diluted with EtOAc (50 mL) and then washed with brine. The organic layer was separated, dried over Na₂SO₄ and concentrated in vacuum. The residue was purified by Prep-TLC (eluent: DCM/MeOH (v/v)=25/1) to afford (4R)-4-isopropyl-1-(2-(2,2,2-trifluoro-1-hydroxyethyl)-2,3-dihydro-1H-inden-2-yl)imidazolidin-2-one (60 mg, yield: 20% for two steps). MS (ESI) m/e [M+1]⁺ 343.2.

Step 5: (4R)-1-(5-amino-2-(2,2,2-trifluoro-1-hydroxyethyl)-2,3-dihydro-1H-inden-2-yl)-4-isopropylimidazolidin-2-one

To the mixture of H₂SO₄ (1 mL) and HNO₃ (1.5 mL) was added a solution of (4R)-4-isopropyl-1-(2-(2,2,2-trifluoro-1-hydroxyethyl)-2,3-dihydro-1H-inden-2-yl)imidazolidin-2-one (60 mg) in AcOH (2 mL) in batches at −5° C. The mixture was further stirred for 5 min at −5° C. The reaction mixture was poured in water/ice and was then extracted with EtOAc (15 mL×3). The combined organic layers were washed with water, aq. NaHCO₃ and brine, dried and concentrated in vacuum. (4R)-1-(5-amino-2-(2,2,2-trifluoro-1-hydroxyethyl)-2,3-dihydro-1H-inden-2-yl)-4-isopropylimidazolidin-2-one (70 mg, crude) was afforded. The crude nitro product was dissolved in MeOH (10 mL), stirred and hydrogenated with H₂ in presence of Pd/C (35 mg) for 1 hour at room temperature. (4R)-1-(5-amino-2-(2,2,2-trifluoro-1-hydroxyethyl)-2,3-dihydro-1H-inden-2-yl)-4-isopropylimidazolidin-2-one (40 mg, crude) was obtained. MS (ESI) m/e [M+1]+358.3.

Step 6: benzyl ((2S)-1,1-dicyclopropyl-3-((2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(2,2,2-trifluoro-1-hydroxyethyl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)carbamate

To a solution of (4R)-1-(5-amino-2-(2,2,2-trifluoro-1-hydroxyethyl)-2,3-dihydro-1H-inden-2-yl)-4-isopropylimidazolidin-2-one (40 mg, crude) in DCM (5 mL) was added (S)-2-(((benzyloxy)carbonyl)amino)-3,3-dicyclopropylpropanoic acid (34 mg, 0.11 mmol), DIPEA (43.4 mg, 0.34 mmol) and HATU (55.4 mg, 0.15 mmol). The mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with DCM (15 mL) and then washed with aq. NaHCO₃. The organic layer was washed with brine, dried and concentrated in vacuum. The crude product was purified by Prep-TLC (eluent: EA/PE (v/v)=1/1). Benzyl ((2S)-1,1-dicyclopropyl-3-((2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(2,2,2-trifluoro-1-hydroxyethyl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)carbamate (30 mg, yield: 42%) was obtained. MS (ESI) m/e [M+1]⁺ 643.5.

Step 7: (2S)-2-amino-3,3-dicyclopropyl-N-(2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(2,2,2-trifluoro-1-hydroxyethyl)-2,3-dihydro-1H-inden-5-yl)propanamide

A solution of benzyl ((2S)-1,1-dicyclopropyl-3-((2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(2,2,2-trifluoro-1-hydroxyethyl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)carbamate (30 mg, 0.05 mmol) in MeOH was added Pd/C (30 mg). This mixture was then degassed with H₂ and stirred at room temperature for 1 hour under H₂ atmosphere. The reaction mixture was diluted with DCM and filtered. The filtrate was concentrated to afford (2S)-2-amino-3,3-dicyclopropyl-N-(2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(2,2,2-trifluoro-1-hydroxyethyl)-2,3-dihydro-1H-inden-5-yl)propanamide (29 mg, crude). MS (ESI) m/e [M+1]⁺ 509.4.

Step 8: N-((2S)-1,1-dicyclopropyl-3-((2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(2,2,2-trifluoro-1-hydroxyethyl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)-4-methyl-1,2,5-oxadiazole-3-carboxamide (Example 238)

To a solution of (2S)-2-amino-3,3-dicyclopropyl-N-(2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(2,2,2-trifluoro-1-hydroxyethyl)-2,3-dihydro-1H-inden-5-yl)propanamide (29 mg, crude) in DCM (5 mL) was added 4-methyl-1,2,5-oxadiazole-3-carboxylic acid (7.3 mg, 0.06 mmol), DIPEA (22 mg, 0.17 mmol) and HATU (33 mg, 0.09 mmol). The mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with DCM (15 mL) and then washed with aq. NaHCO₃. The organic layer was washed with brine, dried and concentrated in vacuum. The residue was firstly purified by prep-TLC. The crude product was then purified by Prep-HPLC (mobile phase: MeCN/water (0.1% FA); column: SunFire; elution: 60%-80% MeCN). The title compound example 238 (8.16 mg, 28% for two steps) was obtained. ¹H NMR (400 MHz, DMSO-d₆) δ ppm: 10.12 (s, 1H), 9.05 (d, J=8.8 Hz, 1H), 7.54-7.50 (m, 1H), 7.43-7.32 (m, 1H), 7.24-7.11 (m, 1H), 6.90-6.76 (m, 1H), 4.87-4.75 (m, 2H), 3.53-3.38 (m, 3H), 3.31-3.14 (m, 4H), 2.97-2.89 (m, 1H), 2.49 (s, 3H), 1.37-1.24 (m, 1H), 0.93-0.67 (m, 3H), 0.63-0.50 (m, 6H), 0.49-0.35 (m, 2H), 0.33-0.08 (m, 6H). MS (ESI) m/e [M+1]⁺ 619.5.

Example 256: N-((2S)-1,1-dicyclopropyl-3-oxo-3-((2-(((S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)methyl)-2,3-dihydrobenzofuran-6-yl)amino)propan-2-yl)-1-isopropyl-1H-pyrazole-5-carboxamide

Step 1: 2-(2,2-dimethoxyethoxy)-4-nitrobenzaldehyde

To a solution of 2-hydroxy-4-nitrobenzaldehyde (10 g, 29.92 mmol) in DMA (100 mL) was added 2-bromo-1,1-dimethoxyethane (40 g, 239.35 mmol), K₂CO₃ (33 g, 239.35 mmol) at room temperature slowly. The mixture was stirred at 140° C. for 12 hrs. The reaction mixture was poured into ice-water (500 mL). The precipitate was collected by filtration and washed with water (500 mL). After the cake was dried in vacuum, 2-(2,2-dimethoxyethoxy)-4-nitrobenzaldehyde (10 g, yield: 66%) was obtained. ¹H NMR (400 MHz, CDCl₃) δ ppm 10.55 (s, 1H), 8.04-7.96 (m, 1H), 7.94-7.86 (m, 2H), 4.81 (t, J=5.2 Hz, 1H), 4.23 (d, J=5.2 Hz, 2H), 3.52-3.44 (m, 6H).

Step 2: 6-nitrobenzofuran-2-carbaldehyde

A solution of 2-(2,2-dimethoxyethoxy)-4-nitrobenzaldehyde (10 g, 39.18 mmol) in AcOH (100 mL) was heated to 60° C. and stirred for 12 hrs. The reaction mixture was concentrated under reduced pressure. The residue was poured into saturated aq. Na₂CO₃ solution (100 mL) and then extracted with DCM (100 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. 6-nitrobenzofuran-2-carbaldehyde (6 g, yield: 80%) was obtained. ¹H NMR (400 MHz, CDCl₃) δ ppm 9.99 (s, 1H), 8.52 (s, 1H), 8.28 (dd, J=2.0, 8.8 Hz, 1H), 7.92 (d, J=8.8 Hz, 1H), 7.65 (d, J=0.4 Hz, 1H).

Step 3: (S)-3,3,3-trifluoro-N¹-((6-nitrobenzofuran-2-yl)methyl)propane-1,2-diamine

To a solution of 6-nitrobenzofuran-2-carbaldehyde (2 g, 10.46 mmol) in i-PrOH (40 mL) was added (S)-3,3,3-trifluoropropane-1,2-diamine hydrochloride (2.58 g, 15.70 mmol) and TEA (4.24 g, 41.85 mmol) at 20° C. The mixture was stirred at 60° C. for 2 hrs. After TLC indicated the aldehyde reactant was consumed completely, AcOH (3.14 g, 52.30 mmol) and NaBH₃CN (1.64 g, 26.16 mmol) were added into the reaction mixture (mainly containing the imine intermediate of (S)-1,1,1-trifluoro-3-(((6-nitrobenzofuran-2-yl)methylene)amino)propan-2-amine in i-PrOH) at 0° C. After addition, the reaction mixture was further stirred at 80° C. for 12 hours. The reaction mixture was cooled and then poured into saturated aq. NaHCO₃ solution (20 mL) and extracted with DCM (50 mL×3). The combined layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: Petroleum ether/Ethyl acetate (v/v)=100/1 to 0/1). (S)-3,3,3-trifluoro-N¹-((6-nitrobenzofuran-2-yl)methyl)propane-1,2-diamine (2.3 g, 70% yield) was obtained. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.37 (d, J=1.2 Hz, 1H), 8.18 (dd, J=2.0, 8.4 Hz, 1H), 7.63 (d, J=8.4 Hz, 1H), 6.74 (s, 1H), 4.05 (s, 2H), 3.36 (s, 1H), 3.37 (s, 1H), 3.00 (dd, J=3.6, 12.4 Hz, 1H), 2.75 (dd, J=8.8, 12.0 Hz, 1H). MS (ESI, m/e) [M+1]⁺ 303.2.

Step 4: (S)-1-((6-nitrobenzofuran-2-yl)methyl)-4-(trifluoromethyl)imidazolidin-2-one

To a solution of (S)-3,3,3-trifluoro-N¹-((6-nitrobenzofuran-2-yl)methyl)propane-1,2-diamine (2.3 g, 7.58 mmol) in THF (20 mL) was added CDI (1.84 g, 11.38 mmol) at room temperature. The mixture was stirred at 80° C. for 2 hrs. The reaction mixture was cooled and poured into water (20 mL), extracted with DCM (20 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The crude product was purified by column chromatography on silica gel (eluent: Petroleum ether/Ethyl acetate (v/v)=50/1 to 1/1). (S)-1-((6-nitrobenzofuran-2-yl)methyl)-4-(trifluoromethyl)imidazolidin-2-one (1.5 g, yield: 60%) was obtained. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.42-8.35 (m, 1H), 8.23-8.15 (m, 1H), 7.67-7.62 (m, 1H), 6.81-6.75 (m, 1H), 5.01-4.94 (m, 1H), 4.68-4.54 (m, 1H), 4.24-4.17 (m, 1H), 3.84-3.62 (m, 2H).

Step 5: (4S)-1-((6-amino-2,3-dihydrobenzofuran-2-yl)methyl)-4-(trifluoromethyl)imidazolidin-2-one

To a solution of (S)-1-((6-nitrobenzofuran-2-yl)methyl)-4-(trifluoromethyl)imidazolidin-2-one (1.5 g, 4.56 mmol) in i-PrOH (10 mL) was added Pd/C (180 mg) at room temperature. The mixture was stirred and hydrogenated under H₂ atmosphere (50 psi) at 50° C. for 12 hrs. The reaction mixture was filtered and concentrated in vacuum. The crude product was purified by column chromatography on silica gel (eluent: Petroleum ether/Ethyl acetate (v/v)=100/1 to 0/1). (4S)-1-((6-amino-2,3-dihydrobenzofuran-2-yl)methyl)-4-(trifluoromethyl)imidazolidin-2-one (810 mg, yield: 59%) was obtained. ¹H NMR (400 MHz, CDCl₃) δ ppm 6.92 (d, J=7.6 Hz, 1H), 6.30-6.11 (m, 2H), 5.16-4.88 (m, 2H), 4.18-4.07 (m, 1 H), 3.84-3.71 (m, 1H), 3.67-3.54 (m, 3H), 3.47-3.29 (m, 1H), 3.18 (ddd, J=3.2, 9.6, 15.2 Hz, 1H), 2.86 (dt, J=7.2, 16.4 Hz, 1H). MS (ESI, m/e) [M+1]⁺ 302.1.

Step 6: benzyl ((2S)-1,1-dicyclopropyl-3-oxo-3-((2-(((S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)methyl)-2,3-dihydrobenzofuran-6-yl)amino)propan-2-yl)carbamate

To a solution of (4S)-1-((6-amino-2,3-dihydrobenzofuran-2-yl)methyl)-4-(trifluoromethyl)imidazolidin-2-one (301 mg, 1.0 mmol) in DCM (100 mL) were added (S)-2-(((benzyloxy)carbonyl)amino)-3,3-dicyclopropylpropanoic acid (303 mg, 1.0 mmol), HATU (380 mg, 1.0 mmol) and TEA (202 mg, 2.0 mmol). The mixture was stirred at room temperature for 4 hrs. The reaction mixture was then quenched with NaHCO₃ (aq, 150 mL). The organic layer was separated, washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The crude product was purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=50/1). benzyl ((2S)-1,1-dicyclopropyl-3-oxo-3-((2-(((S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)methyl)-2,3-dihydrobenzofuran-6-yl)amino)propan-2-yl)carbamate (469 mg, 80%) was obtained. MS (ESI, m/e) [M+1]⁺ 587.2.

Step 7: (2S)-2-amino-3,3-dicyclopropyl-N-(2-(((S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)methyl)-2,3-dihydrobenzofuran-6-yl)propanamide

To the mixture of benzyl ((2S)-1,1-dicyclopropyl-3-oxo-3-((2-(((S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)methyl)-2,3-dihydrobenzofuran-6-yl)amino)propan-2-yl)carbamate (469 mg, 0.8 mmol) and Pd/C (50 mg) in MeOH (50 mL) was bubbled with H₂ balloon and stirred for 2 hrs. The mixture was filtrated and concentrated in vacuum. The crude product (2S)-2-amino-3,3-dicyclopropyl-N-(2-(((S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)methyl)-2,3-dihydrobenzofuran-6-yl)propanamide (226 mg, crude) was obtained, which was used in next step directly. MS (ESI, m/e) [M+1]⁺ 453.2.

Step 8: N-((2S)-1,1-dicyclopropyl-3-oxo-3-((2-(((S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)methyl)-2,3-dihydrobenzofuran-6-yl)amino)propan-2-yl)-1-isopropyl-1H-pyrazole-5-carboxamide

Example 256

To a solution of (2S)-2-amino-3,3-dicyclopropyl-N-(2-(((S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)methyl)-2,3-dihydrobenzofuran-6-yl)propanamide (226 mg, 0.5 mmol) in DCM (50 mL) were added 1-isopropyl-1H-pyrazole-5-carboxylic acid (14 mg, 0.09 mmol), HATU (40 mg, 0.09 mmol) and DIEA (23 mg, 0.18 mmol). The mixture was stirred at room temperature for 4 hrs. The reaction mixture was quenched with saturated aq. NaHCO₃ (50 mL). The organic layer was separated, washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The residue was purified by Prep-TLC (eluent: MeOH/DCM (v/v)=1/20) to give the crude product. The crude product was purified by prep-HPLC. N-((2S)-1,1-dicyclopropyl-3-oxo-3-((2-(((S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)methyl)-2,3-dihydrobenzofuran-6-yl)amino)propan-2-yl)-1-isopropyl-1H-pyrazole-5-carboxamide (16.85 mg, 32.3%) was obtained. ¹H NMR (400 MHz, DMSO-d₆) δ ppm: 10.09 (d, J=5.0 Hz, 1H), 8.42 (d, J=8.7 Hz, 1H), 7.52-7.50 (m, 2H), 7.18 (d, J=4.4 Hz, 1H), 7.10 (t, J=8.4 Hz, 1H), 7.00 (d, J=7.8 Hz, 1H), 6.92 (s, 1H), 5.44-5.37 (m, 1H), 4.95-4.93 (m, 1H), 4.76 (t, J=8.2 Hz, 1H), 4.35 (s, 1H), 3.79-3.66 (m, 1H), 3.58-3.37 (m, 2H), 3.30-3.14 (m, 2H), 2.87-2.82 (m, 1H), 1.38-1.33 (m, 6H), 0.89-0.67 (m, 3H), 0.45-0.06 (m, 8H). MS (ESI, m/e) [M+1]⁺ 589.5.

Example 261: N-((2S)-1,1-dicyclopropyl-3-((2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(o-tolylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)-4-methyl-1,2,5-oxadiazole-3-carboxamide

To a solution of 5-((S)-2-amino-3,3-dicyclopropylpropanamido)-2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-N-(o-tolyl)-2,3-dihydro-1H-indene-2-carboxamide (65 mg, 0.12 mmol) in DCM (5 mL) was added 4-methyl-1,2,5-oxadiazole-3-carboxylic acid (23 mg, 0.18 mmol), HATU (68 mg, 0.18 mmol) and DIEA (31 mg, 0.24 mmol) at 0° C. The mixture was stirred at room temperature for 12 hrs. The reaction mixture was diluted with water (3 mL), extracted with DCM (5 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated in vacuum. The crude product was purified by prep-HPLC (column: Phenomenex Luna C18 75*30 mm*3 um; mobile phase: [water(NH4HCO3)-ACN]; B %: 40%-70%, 8 min). N-((2S)-1,1-dicyclopropyl-3-((2-((R)-4-isopropyl-2-oxoimidazolidin-1-yl)-2-(o-tolylcarbamoyl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)-4-methyl-1,2,5-oxadiazole-3-carboxamide (15.5 mg, yield: 19.8%) was obtained. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.10 (s, 1H), 9.07-8.96 (m, 2H), 7.56-7.47 (m, 1H), 7.46-7.32 (m, 2H), 7.19 (d, J=7.6 Hz, 2H), 7.16-7.10 (m, 1H), 7.08-7.03 (m, 1H), 7.02 (s, 1H), 4.86 (t, J=8.0 Hz, 1H), 3.70 (t, J=17.6 Hz, 1H), 3.62-3.49 (m, 2H), 3.48-3.38 (m, 1H), 3.30-3.25 (m, 1H), 3.22 (d, J=16.4 Hz, 1H), 2.94 (td, J=7.6, 12.4 Hz, 1H), 2.49 (s, 3H), 2.17 (s, 3H), 1.55-1.42 (m, 1H), 0.93-0.84 (m, 1H), 0.82-0.68 (m, 8H), 0.52-0.36 (m, 2H), 0.34-0.11 (m, 6H). MS (ESI, m/e) [M+1]⁺ 654.2.

Example 279: N-((2S)-1,1-dicyclopropyl-3-((2-(2-hydroxypropan-2-yl)-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)-4-methyl-1,2,5-oxadiazole-3-carboxamide

Step 1: 2-(2-amino-2,3-dihydro-1H-inden-2-yl)propan-2-ol

Methyl 2-amino-2,3-dihydro-1H-indene-2-carboxylate (1 g, 5.2 mmol) was dissolved into THF (20 mL) and cooled to 0° C. under N₂ atmosphere. To this solution was added CH₃MgBr (26.2 mL, 26.2 mmol) dropwise with stirring below 10° C. The mixture was warmed to room temperature and stirred for 30 min. The reaction mixture was quenched with aq. NH₄Cl at 0° C. and was extracted with DCM (30 mL×3). The combined organic layers were washed with brine, dried and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=10/1). 2-(2-amino-2,3-dihydro-1H-inden-2-yl)propan-2-ol (980 mg, yield: 98%) was obtained. MS (ESI) m/e [M+1]⁺ 192.2.

Step 2: benzyl (1,1,1-trifluoro-3-((2-(2-hydroxypropan-2-yl)-2,3-dihydro-1H-inden-2-yl)amino)-3-oxopropan-2-yl)carbamate

To the mixture of 2-(((benzyloxy)carbonyl)amino)-3,3,3-trifluoropropanoic acid (1.4 g, 5.1 mmol), EDCI (2.5 g, 12.8 mmol) and HOBt (727 mg, 5.4 mmol) in DCM (30 mL) were added 2-(2-amino-2,3-dihydro-1H-inden-2-yl)propan-2-ol (980 mg, 5.1 mmol) and TEA (1.6 g, 15.4 mmol) at 0° C. The mixture was warmed to room temperature and stirred for 1.5 hrs. The reaction mixture was diluted with DCM and quenched by NaHCO₃ (aq.). The organic layer was washed with brine, dried and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: PE/EA (v/v)=1/1). Benzyl (1,1,1-trifluoro-3-((2-(2-hydroxypropan-2-yl)-2,3-dihydro-1H-inden-2-yl)amino)-3-oxopropan-2-yl)carbamate (400 mg, yield: 17%) was obtained. MS (ESI) m/e [M+1]⁺ 451.3.

Step 3: benzyl (1,1,1-trifluoro-3-((2-(2-hydroxypropan-2-yl)-2,3-dihydro-1H-inden-2-yl)amino)propan-2-yl)carbamate

Benzyl (1,1,1-trifluoro-3-((2-(2-hydroxypropan-2-yl)-2,3-dihydro-1H-inden-2-yl)amino)-3-oxopropan-2-yl)carbamate (400 mg, 0.89 mmol) was added into BH₃-THF (1M, 10 mL) under stirring. The mixture was heated to 60° C. and stirred for 6 hrs. The reaction mixture was cooled to room temperature and quenched by MeOH (5 mL) at 0° C. The mixture was concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: DCM/MeOH (v/v)=25/1). Benzyl (1,1,1-trifluoro-3-((2-(2-hydroxypropan-2-yl)-2,3-dihydro-1H-inden-2-yl)amino)propan-2-yl)carbamate (110 mg, yield: 28%) was obtained. MS (ESI) m/e [M+1]⁺ 437.3.

Step 4: benzyl (3-((2-(2-((tert-butyldimethylsilyl)oxy)propan-2-yl)-2,3-dihydro-1H-inden-2-yl)amino)-1,1,1-trifluoropropan-2-yl)carbamate

To a solution of benzyl (1,1,1-trifluoro-3-((2-(2-hydroxypropan-2-yl)-2,3-dihydro-1H-inden-2-yl)amino)propan-2-yl)carbamate (110 mg, 0.25 mmol) in DCM (5 mL) were added 2,6-lutidine (40.5 mg, 0.38 mmol) and TBS-OTf (86.6 mg, 0.33 mmol) dropwise at 0° C. under N₂ atmosphere. The mixture was stirred at 0° C. for 1 hour. The reaction mixture was quenched by aq. NaHCO₃ (10 mL) at 0° C. and was extracted with EtOAc (10 mL×3). The combined organic layers were washed with brine, dried and concentrated in vacuum. The residue was purified by column chromatography on silica gel (eluent: PE/EA (v/v)=3/1). Benzyl (3-((2-(2-((tert-butyldimethylsilyl)oxy)propan-2-yl)-2,3-dihydro-1H-inden-2-yl)amino)-1,1,1-trifluoropropan-2-yl)carbamate (110 mg, yield: 79%) was obtained. MS (ESI) m/e [M+1]⁺ 551.4.

Step 5: N¹-(2-(2-((tert-butyldimethylsilyl)oxy)propan-2-yl)-2,3-dihydro-1H-inden-2-yl)-3,3,3-trifluoropropane-1,2-diamine

To the solution of benzyl (3-((2-(2-((tert-butyldimethylsilyl)oxy)propan-2-yl)-2,3-dihydro-1H-inden-2-yl)amino)-1,1,1-trifluoropropan-2-yl)carbamate (110 mg, 0.2 mmol) in MeOH (5 mL) was added Pd/C (55 mg). This mixture was then degassed with H₂ and stirred at room temperature for 1 hour at H₂ atmosphere. The reaction mixture was diluted with DCM (5 mL) and then filtered. The filtrate was concentrated in vacuum. N¹-(2-(2-((tert-butyldimethylsilyl)oxy)propan-2-yl)-2,3-dihydro-1H-inden-2-yl)-3,3,3-trifluoropropane-1,2-diamine (84 mg, crude) was obtained, which was used directly in next step. MS (ESI) m/e [M+1]⁺ 417.4.

Step 6: 1-(2-(2-((tert-butyldimethylsilyl)oxy)propan-2-yl)-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one

To a solution of N¹-(2-(2-((tert-butyldimethylsilyl)oxy)propan-2-yl)-2,3-dihydro-1H-inden-2-yl)-3,3,3-trifluoropropane-1,2-diamine (84 mg, 0.2 mmol) in THF (6 mL) was added CDI (82 mg, 0.5 mmol) and TEA (102 mg, 1.0 mmol) at room temperature. The mixture was heated to 60° C. and stirred for 2 hrs. The reaction mixture was then cooled to room temperature, diluted with EtOAc (20 mL) and washed with brine. The organic layer was dried and concentrated in vacuum. The residue was purified by Prep-TLC (eluent: EtOAc/DCM (v/v)=2/1). 1-(2-(2-((tert-butyldimethylsilyl)oxy)propan-2-yl)-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one (80 mg, crude) was obtained. MS (ESI) m/e [M+1]+443.3.

Step 7: 1-(2-(2-hydroxypropan-2-yl)-5-nitro-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one

To the mixture of H₂SO₄ (2 mL) and HNO₃ (3 mL) was added a solution of (1-(2-(2-((tert-butyldimethylsilyl)oxy)propan-2-yl)-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one (80 mg) in AcOH (2 mL) in batches at −5° C. The mixture was further stirred for 5 min at −5° C. The reaction mixture was poured in water/ice and was then extracted with EtOAc (15 mL×3). The combined organic layers were washed with water, aq. NaHCO₃ and brine, dried and concentrated in vacuum. 1-(2-(2-hydroxypropan-2-yl)-5-nitro-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one (50 mg, crude) was obtained. MS (ESI) m/e [M+23]⁺ 374.2.

Step 8: 1-(5-amino-2-(2-hydroxypropan-2-yl)-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one

To a solution of 1-(2-(2-hydroxypropan-2-yl)-5-nitro-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one (50 mg, crude) in MeOH (6 mL) was added Pd/C (30 mg). The mixture was then degassed with H₂ and stirred at room temperature for 1 hour. The reaction mixture was diluted with DCM (15 mL) and filtered. The filtrate was concentrated in vacuum. 1-(5-amino-2-(2-hydroxypropan-2-yl)-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one (40 mg, crude) was obtained. MS (ESI) m/e [M+1]⁺ 344.2.

Step 9: benzyl ((2S)-1,1-dicyclopropyl-3-((2-(2-hydroxypropan-2-yl)-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)carbamate

To a solution of 1-(5-amino-2-(2-hydroxypropan-2-yl)-2,3-dihydro-1H-inden-2-yl)-4-(trifluoromethyl)imidazolidin-2-one (40 mg, 0.11 mmol) in DCM (5 mL) was added (S)-2-(((benzyloxy)carbonyl)amino)-3,3-dicyclopropylpropanoic acid (35 mg, 0.11 mmol), DIPEA (45 mg, 0.35 mmol) and HATU (66 mg, 0.17 mmol). The mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with DCM (15 mL) and was washed with aq. NaHCO₃. The organic layer was washed with brine, dried and concentrated in vacuum. The residue was purified by Prep-TLC (eluent: EtOAc/DCM (v/v)=1/1). Benzyl ((2S)-1,1-dicyclopropyl-3-((2-(2-hydroxypropan-2-yl)-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)carbamate (30 mg, 3 step yield: 41%) was obtained. MS (ESI) m/e [M+1]⁺ 629.1.

Step 10: (2S)-2-amino-3,3-dicyclopropyl-N-(2-(2-hydroxypropan-2-yl)-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)propanamide

To a solution of benzyl ((2S)-1,1-dicyclopropyl-3-((2-(2-hydroxypropan-2-yl)-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)carbamate (30 mg, 0.05 mmol) in MeOH (6 mL) was added Pd/C (30 mg). The mixture was then degassed with H₂ and stirred for 1 hour under H₂ atmosphere. The reaction mixture was diluted with DCM (10 mL) and filtered. The filtrate was concentrated in vacuum. (2S)-2-amino-3,3-dicyclopropyl-N-(2-(2-hydroxypropan-2-yl)-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)propanamide (28 mg, crude) was obtained. MS (ESI) m/e [M+1]⁺ 495.2.

Step 11: N-((2S)-1,1-dicyclopropyl-3-((2-(2-hydroxypropan-2-yl)-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)amino)-3-oxopropan-2-yl)-4-methyl-1,2,5-oxadiazole-3-carboxamide (Example 279)

To a solution of (2S)-2-amino-3,3-dicyclopropyl-N-(2-(2-hydroxypropan-2-yl)-2-(2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)-2,3-dihydro-1H-inden-5-yl)propanamide (28 mg, crude) in DCM (5 mL) was added 4-methyl-1,2,5-oxadiazole-3-carboxylic acid (7.3 mg, 0.06 mmol), DIPEA (22 mg, 0.17 mmol) and HATU (33 mg, 0.09 mmol). The mixture was stirred for 1 hour at room temperature. The reaction mixture was diluted with DCM (15 mL) and then washed with aq. NaHCO₃. The organic layer was washed with brine, dried and concentrated in vacuum. The residue was firstly purified by prep-TLC. The crude product was further purified by Prep-HPLC (mobile phase: MeCN/water (0.1% FA); column: SunFire; elution: 50%-68% MeCN). The title compound example 279 (10 mg, yield: 29% for two steps) was obtained. ¹H NMR (400 MHz, DMSO-d₆) δ ppm: 10.06 (s, 1H), 9.01 (d, J=8.8 Hz, 1H), 7.46 (t, J=9.4 Hz, 1H), 7.34-7.30 (m, 2H), 7.12 (d, J=7.8 Hz, 1H), 5.21 (s, 1H), 4.85 (t, J=7.8 Hz, 1H), 4.23 (s, 1H), 3.83-3.57 (m, 3H), 3.43-3.18 (m, 3H), 2.48 (s, 3H), 1.10 (s, 6H), 0.93-0.62 (m, 3H), 0.52-0.11 (m, 8H). MS (ESI) m/e [M+1]⁺ 605.2.

Other examples were synthesized according to the similar methods with Example 32 or Example 170, Example 212, Example 238, Example 256, Example 261, Example 279 which are known to those skilled in this art. The corresponding compound name, structure and spectrum data were listed in the Table.

Ex.	structure	Compound name
1		N-((1S)-1-cyclohexyl- 2-((2-(4-methyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
2		N-((1S)-1-cyclohexyl- 2-((2-(methoxymethyl)- 2-(4-methyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
3		N-((1S)-1-cyclohexyl- 2-((2-(4-methyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
4		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
5		2-((S)-cyclohexyl(1- methyl-1H-pyrazole-5- carboxamido)methyl)- N-methyl-6-(4-methyl- 2-oxoimidazolidin-1- yl)-1,5,6,7- tetrahydroindeno[5,6- d]imidazole-6- carboxamide
6		N-((1S)-1-cyclohexyl- 2-((3-(4-methyl-2- oxoimidazolidin-1-yl)- 3-(methylcarbamoyl)- 3,4-dihydro-2H- benzo[b][1,4]dioxepin- 7-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
7		N-((1S)-1-cyclohexyl- 2-((7-(4-methyl-2- oxoimidazolidin-1-yl)- 7-(methylcarbamoyl)- 6,7,8,9-tetrahydro-5H- benzo[7]annulen-2- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
8		N-((1S)-1-cyclohexyl- 2-((1-(4-methyl-2- oxoimidazolidin-1-yl)- 1-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
9		N-((1S)-1-cyclohexyl- 2-((5-(4-methyl-2- oxoimidazolidin-1-yl)- 5-(methylcarbamoyl)- 5,6-dihydro-4H- cyclopenta[b]thiophen- 2-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
10		N-((1S)-1-cyclohexyl- 2-((7-(4-methyl-2- oxoimidazolidin-1-yl)- 7-(methylcarbamoyl)- 5,6,7,8- tetrahydronaphthalen-2- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
11		N-((1S)-1-cyclohexyl- 2-((2-((4-methyl-2- oxoimidazolidin-1- yl)methyl)benzofuran- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
12		N-((1S)-1-cyclohexyl- 2-((2-((4-methyl-2- oxoimidazolidin-1- yl)methyl)-1H-indol-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
13		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (2-oxoimidazolidin-1- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
14		N-((1S)-cyclohexyl(6- (4-methyl-2- oxoimidazolidin-1-yl)- 6-(methylcarbamoyl)- 1,5,6,7- tetrahydroindeno[5,6- d]imidazol-2- yl)methyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
15		N-((1S)-2-((2- carbamoyl-2-(4-methyl- 2-oxoimidazolidin-1- yl)-2,3-dihydro-1H- inden-5-yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
16		N-((2S)-3-cyclohexyl- 1-((2-(4-methyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- oxopropan-2-yl)-1- methyl-1H-pyrazole-5- carboxamide
17		N-((1S)-1-cyclohexyl- 2-((2-(5-methyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
18		N-((1S)-1-cyclohexyl- 2-((2-((S)-4-ethyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
19		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-ethyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
20		N-((1S)-1-cyclohexyl- 2-((2-(4,4-dimethyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
21		N-((1S)-1-cyclohexyl- 2-((2-((4-methyl-2- oxoimidazolidin-1- yl)methyl)-2,3- dihydrobenzofuran-6- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
22		N-((1S)-1-cyclohexyl- 2-((2-(hydroxymethyl)- 2-(4-methyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
23		5-((S)-2-cyclohexyl-2- (1-methyl-1H-pyrazole- 5- carboxamido) acetamido)- 2-(4-methyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-indene- 2-carboxylic acid
24		N-((1S)-1-cyclohexyl- 2-((2-(4-isobutyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
25		N-((1S)-1-cyclohexyl- 2-((2-((R)-4- cyclohexyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
26		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (2-oxo-4- propylimidazolidin-1- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
27		N-((1S)-2-((2-(4- cyclobutyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
28		2-((S)-cyclohexyl(1- methyl-1H-pyrazole-5- carboxamido)methyl)- 6-(4-isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-1,5,6,7- tetrahydroindeno[5,6- d]imidazole-6- carboxamide
29		N-((1S)-cyclohexyl(6- (4-isopropyl-2- oxoimidazolidin-1-yl)- 6-(methylcarbamoyl)- 1,5,6,7- tetrahydroindeno[5,6- d]imidazol-2- yl)methyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
30		N-((1S)-1-cyclohexyl- 2-((2-(4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
31		2-((S)-cyclohexyl(1- methyl-1H-pyrazole-5- carboxamido)methyl)- 6-((R)-4-ethyl-2- oxoimidazolidin-1-yl)- N-methyl-1,5,6,7- tetrahydroindeno[5,6- d]imidazole-6- carboxamide
33		N-((1S)-cyclohexyl(6- ((S)-4-ethyl-2- oxoimidazolidin-1-yl)- 6-(methylcarbamoyl)- 1,5,6,7- tetrahydroindeno[5,6- d]imidazol-2- yl)methyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
34		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (2-oxo-4- (tetrahydrofuran-3- yl)imidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
35		N-((1S)-1-cyclohexyl- 2-((2-(4-(1- methoxypropan-2-yl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
36		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (2-oxo-4- phenylimidazolidin-1- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
37		N-((1S)-2-((2-((R)-4- benzyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
38		N-((1S)-1-cyclohexyl- 2-((2-(4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
39		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
40		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 4-methyl-1,2,5- oxadiazole-3- carboxamide
41		N-((1S)-1-cyclohexyl- 2-((2-((R)-4- cyclopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
42		N-((1S)-1-cyclohexyl- 2-((2-(4-(2- hydroxypropan-2-yl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
43		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- ((R)-2-oxo-4-(pyridin- 2- ylmethyl)imidazolidin- 1-yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
44		N-((1S)-2-((2-(4-(tert- butyl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
45		N-((1S)-1-cyclobutyl-2- ((2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
46		N-((1S)-1-cyclopentyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
47		N-((1S)-1-cycloheptyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
48		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (2-oxo-4-(1- phenylethyl)imidazolidin- 1-yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
49		5-((S)-2-cyclohexyl-2- (cyclopropanecarboxamido) acetamido)-2-((R)- 4-isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-2,3-dihydro- 1H-indene-2- carboxamide
50		ethyl ((1S)-1- cyclohexyl-2-((2-((R)- 4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)carbamate
51		phenyl ((1S)-1- cyclohexyl-2-((2-((R)- 4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)carbamate
52		5-((S)-2-cyclohexyl-2- (3- phenylpropanamido) acetamido)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-2,3-dihydro- 1H-indene-2- carboxamide
53		5-((S)-2-cyclohexyl-2- (2- phenylacetamido) acetamido)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-2,3-dihydro- 1H-indene-2- carboxamide
54		5-((S)-2-benzamido-2- cyclohexylacetamido)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-2,3-dihydro- 1H-indene-2- carboxamide
55		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 1,1-dioxido-1,2,5- thiadiazolidin-2-yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
56		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-(4- methoxybenzyl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
57		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- ((R)-2-oxo-4-(thiophen- 2- ylmethyl)imidazolidin- 1-yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
58		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2- oxoethyl)nicotinamide
59		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-isopropyl-1H- pyrazole-5-carboxamide
60		N-((1S)-2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2-oxo-1- phenylethyl)-1-methyl- 1H-pyrazole-5- carboxamide
61		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 4-carboxamide
62		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-(4- methylbenzyl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
63		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (2-oxo-4-(prop-2-yn-1- yl)imidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
64		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-1,2,4- triazole-5-carboxamide
65		N-((1S)-1-cyclohexyl- 2-((2-(4- (cyclopropylmethyl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
66		N-((2S)-1-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1-oxo-3- phenylpropan-2-yl)-1- methyl-1H-pyrazole-5- carboxamide
67		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
68		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2-((2,2,2- trifluoroethyl)carbamoyl)- 2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
69		5-((S)-2-(3- chlorobenzamido)-2- cyclohexylacetamido)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-2,3-dihydro- 1H-indene-2- carboxamide
70		N-((1S)-1-cyclohexyl- 2-((2-(5,5-dimethyl-2- oxotetrahydropyrimidin- 1(2H)-yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
71		5-((S)-2-cyclohexyl-2- (3- methylbenzamido) acetamido)- 2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-2,3-dihydro- 1H-indene-2- carboxamide
72		N-(2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1-(4- methoxycyclohexyl)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
73		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (2-oxo-4-(2,2,2- trifluoroethyl) imidazolidin- 1-yl)-2,3-dihydro- 1H-inden-5-yl)amino)- 2-oxoethyl)-1-methyl- 1H-pyrazole-5- carboxamide
74		N-((1S)-2-((2-(4-(4- chlorobenzyl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
75		N-((1S)-1-cyclohexyl- 2-((2-(5-ethyl-2- oxotetrahydropyrimidin- 1(2H)-yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
76		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-(4- fluorobenzyl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
77		5-((S)-2- (benzo[d]oxazol-2- ylamino)-2- cyclohexylacetamido)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-2,3-dihydro- 1H-indene-2- carboxamide
78		5-((S)-2-cyclohexyl-2- (4- methylbenzamido) acetamido)- 2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-2,3-dihydro- 1H-indene-2- carboxamide
79		N-((2S)-3-(2-chloro-5- (2-(2-hydroxypropan-2- yl)pyridin-4-yl)phenyl)- 1-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-1-oxopropan- 2-yl)-1-methyl-1H- pyrazole-5-carboxamide
80		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (2-oxo-4-(4- (trifluoromethyl)benzyl) imidazolidin-1-yl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
81		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (2-oxo-4-(1,1,1- trifluoropropan-2- yl)imidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
82		N-((1S)-1-cycloheptyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2-((methyl- d3)carbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
83		N-((1S)-2-((2- carbamoyl-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- cycloheptyl-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
84		5-((S)-2-cyclohexyl-2- (3- isopropoxybenzamido) acetamido)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-2,3-dihydro- 1H-indene-2- carboxamide
85		N-((1S)-2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2-oxo-1- (tetrahydro-2H-pyran-4- yl)ethyl)-1-methyl-1H- pyrazole-5-carboxamide
86		N-((1S)-2-((2-((1- cyclobutyl-2- hydroxyethyl) carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
87		N-(1-(4,4- dimethylcyclohexyl)-2- ((2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
88		N-((1S)-1-cyclohexyl- 2-((2-(4- (cyclohexylmethyl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
89		N-(2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1-(4- methylcyclohexyl)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
90		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-1- methyl-1H-pyrazole-5- carboxamide
91		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-1- isopropyl-1H-pyrazole- 5-carboxamide
92		N-((1S)-1-cyclohexyl- 2-((2-(4-(2,3-dihydro- 1H-inden-1-yl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
93		N-((2R)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-1- methyl-1H-pyrazole-5- carboxamide
94		N-((1S)-1-cyclohexyl- 2-((2-(5-cyclopropyl-2- oxotetrahydropyrimidin- 1(2H)-yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
95		N-((1S)-1-cyclohexyl- 2-((2-(4-methyl-2- oxotetrahydropyrimidin- 1(2H)-yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
96		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- ((R)-2-oxo-4- phenethylimidazolidin- 1-yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
97		N-(1-(2,3-dihydro-1H- inden-1-yl)-2-((2-((R)- 4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
98		N-((1S)-1-cyclohexyl- 2-((2-(5-methyl-2- oxotetrahydropyrimidin- 1(2H)-yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
99		N-((1S)-2-((2-(5- benzyl-2- oxotetrahydropyrimidin- 1(2H)-yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
100		N-((1S)-1-cyclohexyl- 2-((2-(5-(4- methoxybenzyl)-5- methyl-2- oxotetrahydropyrimidin- 1(2H)-yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
101		N-(1-(4- ethylcyclohexyl)-2-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
102		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
103		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-(2-hydroxyethyl)-1H- pyrazole-3-carboxamide
104		N-(2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1-(3- methylcyclohexyl)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
105		N-((1S)-1-cyclohexyl- 2-((2-(5-ethyl-5-methyl- 2- oxotetrahydropyrimidin- 1(2H)-yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
106		N-((1S)-2-((2-(4-(but-2- yn-1-yl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
107		N-((1S)-1-cyclohexyl- 2-((2-((1-cyclopentyl-2- hydroxyethyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
108		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (7-oxo-6,8- diazaspiro[3.5]nonan-6- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
109		N-((1S)-2-((2-(5- benzyl-5-methyl-2- oxotetrahydropyrimidin- 1(2H)-yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
110		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (7-oxo-6,8- diazaspiro[3.5]nonan-6- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
111		[0344] N-(1- ((1R,3S,5R,7R)- adamantan-2-yl)-2-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
112		N-(2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2-oxo-1- (spiro[2.5]octan-6- yl)ethyl)-1-methyl-1H- pyrazole-5-carboxamide
113		N-((1S)-1-cyclohexyl- 2-((2-(5-cyclopropyl-5- methyl-2- oxotetrahydropyrimidin- 1(2H)-yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
114		N-((2S)-1,1- dicyclopropyl-3-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-3- oxopropan-2-yl)-1- methyl-1H-pyrazole-5- carboxamide
115		N-((2S)-1,1- dicyclopropyl-3-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-3- oxopropan-2-yl)-1- isopropyl-1H-pyrazole- 5-carboxamide
116		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
117		3-((S)-2-cyclohexyl-2- (1-methyl-1H-pyrazole- 5- carboxamido)acetamido)- 6-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-6,7-dihydro- 5H- cyclopenta[b]pyridine- 6-carboxamide
118		N-(1-(4-(tert- butyl)cyclohexyl)-2-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
119		N-((1S)-1-cyclohexyl- 2-((6-fluoro-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
120		N-((2S)-1,1- dicyclopropyl-3-((2- (methylcarbamoyl)-2- (7-oxo-6,8- diazaspiro[3.5]nonan-6- yl)-2,3-dihydro-1H- inden-5-yl)amino)-3- oxopropan-2-yl)-1- methyl-1H-pyrazole-5- carboxamide
121		N-((1S)-1-cyclohexyl- 2-((2-(((S)-1- cyclohexyl-2- hydroxyethyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
122		N-((1S)-1-cyclohexyl- 2-((2-(((R)-1- cyclohexyl-2- hydroxyethyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
123		2-((S)-cyclohexyl(1- methyl-1H-pyrazole-5- carboxamido)methyl)- 6-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-5,6,7,8- tetrahydro-1H- naphtho[2,3- d]imidazole-6- carboxamide
124		N-((1S)-1-cyclohexyl- 2-((2- (isobutylcarbamoyl)-2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
125		N-(1-(4- ethylcyclohexyl)-2-((2- (methylcarbamoyl)-2- (7-oxo-6,8- diazaspiro[3.5]nonan-6- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
126		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-(2-hydroxyethyl)-1H- pyrazole-5-carboxamide
127		N-(3-(2,5- dichlorophenyl)-1-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- oxopropan-2-yl)-1- methyl-1H-pyrazole-5- carboxamide
128		N-(2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2-oxo-1- (1,2,3,4- tetrahydronaphthalen-2- yl)ethyl)-1-methyl-1H- pyrazole-5-carboxamide
129		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-cyclopropyl-1H- pyrazole-5-carboxamide Chemical Formula: C32H43N704
130		4-cyano-N-((1S)-1- cyclohexyl-2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrrole-2-carboxamide
131		5-cyano-N-((1S)-1- cyclohexyl-2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrrole-2-carboxamide
132		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-(3- hydroxycyclobutyl)-1H- pyrazole-5-carboxamide
133		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-(3- hydroxycyclobutyl)-1H- pyrazole-3-carboxamide
134		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (2- oxotetrahydropyrimidin- 1(2H)-yl)-2,3-dihydro- 1H-inden-5-yl)amino)- 2-oxoethyl)-1-methyl- 1H-pyrazole-5- carboxamide
135		N-((1S)-1-cyclohexyl- 2-((2- (dimethylcarbamoyl)-2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
136		N-((1S)-1-cyclohexyl- 2-((2-(3- hydroxypyrrolidine-1- carbonyl)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
137		2-((S)-cyclohexyl(1- methyl-1H-pyrazole-5- carboxamido)methyl)- N-methyl-6-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-1,5,6,7- tetrahydroindeno[5,6- d]imidazole-6- carboxamide
138		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-(methylcarbamoyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
139		N-(1-(4- ethylcyclohexyl)-2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
140		N-((1S)-2-((2-(4-(4- cyanobenzyl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
141		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1- cyclopropyl-1H- pyrazole-5-carboxamide
142		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-(methylcarbamoyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
143		N-(1-(4-(1,1- difluoroethyl)cyclohexyl)- 2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
144		N-((1S)-1-cyclohexyl-2- ((2-(methylcarbamoyl)- 2-(3-oxo-2,4- diazabicyclo[3.2.1]octan- 2-yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
146		N-((1S)-1-cyclohexyl- 2-oxo-2-((2-((S)-2-oxo- 4- (trifluoromethyl) imidazolidin-1-yl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-1- methyl-1H-pyrazole-5- carboxamide
147		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (8-oxo-7,9- diazaspiro[4.5]decan-7- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
148		methyl 5-(2-(4- isopropylcyclohexyl)-2- (1-methyl-1H-pyrazole- 5- carboxamido)acetamido)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- indene-2-carboxylate
149		5-((S)-2-cyclohexyl-2- (3-((3,5-dimethyl-1H- pyrazol-4- yl)oxy)benzamido) acetamido)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-2,3-dihydro- 1H-indene-2- carboxamide
150		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2-((4- methoxybenzyl)carbam oyl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
151		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (phenylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
152		N-(1-(4- isopropylcyclohexyl)-2- ((2-(methylcarbamoyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
153		5-((S)-2-(3- cyanobenzamido)-2- cyclohexylacetamido)- N-methyl-2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- indene-2-carboxamide
154		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide
155		N-((1S)-2-((2- (((3R,5R)-adamantan-1- yl)carbamoyl)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
156		N-((1S)-1-cyclohexyl- 2-((2-(methoxymethyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
157		5-cyano-N-((1S)-1- cyclohexyl-2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1- cyclopropyl-1H- pyrrole-2-carboxamide
158		5-((S)-2-(2-(3- cyanophenyl)-2,2- difluoroacetamido)-2- cyclohexylacetamido)- N-methyl-2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- indene-2-carboxamide
159		N-((2S)-1,1- dicyclopropyl-3-((2- (methoxymethyl)-2-(6- oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-3- oxopropan-2-yl)-1- methyl-1H-pyrazole-5- carboxamide
160		N-((2S)-1,1- dicyclopropyl-3-((2- (methoxymethyl)-2-(6- oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-3- oxopropan-2-yl)-1- isopropyl-1H-pyrazole- 5-carboxamide
161		N-((1S)-1-cyclohexyl-2- oxo-2-((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2- ((phenylamino)methyl)- 2,3-dihydro-1H-inden- 5-yl)amino)ethyl)-1- methyl-1H-pyrazole-5- carboxamide
162		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
163		N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2-((pyridin-2- ylmethyl)carbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
164		1-methyl-N-(2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxo-1-(4- (trifluoromethyl)cycloh exyl)ethyl)-1H- pyrazole-5-carboxamide
165		N-((1S)-1-((1r,4S)-4- ethylcyclohexyl)-2-((2- (methoxymethyl)-2-(6- oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
166		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-ethyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-1- methyl-1H-pyrazole-5- carboxamide
167		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-fluoro-1- methyl-1H-pyrazole-5- carboxamide
168		1-methyl-N-(2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxo-1-(4-(2,2,2- trifluoroethyl)cyclohexyl) ethyl)-1H-pyrazole-5- carboxamide
169		N-((1S)-2-((2-(1H- benzo[d]imidazol-2-yl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
171		N-((1S)-1-((1r,4S)-4- ethylcyclohexyl)-2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
172		N-((1S)-1-cyclohexyl-2- ((2-(((2- fluorophenyl)amino) methyl)-2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
173		N-((1S)-1-cyclohexyl-2- ((2-(((2- methoxyphenyl)amino) methyl)-2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
174		N-((1S)-1-cyclohexyl- 2-((2-(2,2-difluoro-7- oxo-6,8- diazaspiro[3.5]nonan-6- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
175		N-((1S)-1-cyclohexyl- 2-((2-((2- fluorobenzyl)carbamoyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
176		5-((S)-2-(2-(5-cyano-1- methyl-1H-pyrrol-2-yl)- 2,2-difluoroacetamido)- 2- cyclohexylacetamido)- N-methyl-2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- indene-2-carboxamide
177		N-((2S)-1,1- dicyclopropyl-3-oxo-3- ((2-((S)-2-oxo-4- (trifluoromethyl) imidazolidin- 1-yl)-2,3- dihydro-1H-inden-5- yl)amino)propan-2-yl)- 1-isopropyl-1H- pyrazole-5-carboxamide
178		N-((1S)-1-(4,4- difluorocyclohexyl)-2- oxo-2-((2-((S)-2-oxo-4- (trifluoromethyl) imidazolidin- 1-yl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
179		N-((1S)-1-cyclohexyl-2- ((2-(5-methyl-2-oxo-5- (trifluoromethyl) tetrahydropyrimidin- 1(2H)-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
180		8-cyano-N-((1S)-1- cyclohexyl-2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)imidazo[1,2- a]pyridine-3- carboxamide
181		4-methyl-N-(2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxo-1-(4- (trifluoromethyl) cyclohexyl) ethyl)-1,2,5- oxadiazole-3- carboxamide
182		N-((1S)-2-((2- (bicyclo[1.1.1]pentan-1- ylcarbamoyl)-2-(6-oxo- 5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
183		N-((2S)-1,1- dicyclopropyl-3-oxo-3- ((2-((S)-2-oxo-4- (trifluoromethyl) imidazolidin- 1-yl)-2,3- dihydro-1H-inden-5- yl)amino)propan-2-yl)- 4-methyl-1,2,5- oxadiazole-3- carboxamide
184		N-((1S)-2-((2-(1H- benzo[d]imidazol-2-yl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-1- (4,4- difluorocyclohexyl)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
185		N-((1S)-2-((2-((2- cyclohexylpropyl) carbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-1- (4,4- difluorocyclohexyl)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
186		N-(1-(6-chloro-1,2,3,4- tetrahydronaphthalen-2- yl)-2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
187		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-(7-fluoro-1H- benzo[d]imidazol-2-yl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
188		5-((S)-2-(4,4- difluorocyclohexyl)-2- (4-methyl-1,2,5- oxadiazole-3- carboxamido) acetamido)- 2-(6-oxo-5,7- diazaspiro [2.5]octan-5- yl)-2,3-dihydro-1H- indene-2-carboxylic acid
189		5-((S)-2-cyclohexyl-2- (1-methyl-1H-pyrazole- 5- carboxamido)acetamido)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- indene-2-carboxylic acid
190		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-((3,3- difluorocyclopentyl) carbamoyl)-2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
191		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-((4,4- difluorocyclohexyl) carbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
192		N-((1S)-1-(4,4- difluorocyclohexyl)-2- oxo-2-((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2-(7- (trifluoromethyl)-1H- benzo[d]imidazol-2-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
193		N-((1S)-1-cyclohexyl-2- oxo-2-((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2-(2,2,2- trifluoroacetyl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-1- methyl-1H-pyrazole-5- carboxamide
194		N-((1S)-1-cyclohexyl-2- oxo-2-((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2-(2,2,2-trifluoro-1- hydroxyethyl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-1- methyl-1H-pyrazole-5- carboxamide
195		N-((1S)-1-cyclohexyl- 2-oxo-2-((2-((S)-2-oxo- 4- (trifluoromethyl) imidazolidin- 1-yl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-1- isopropyl-1H-pyrazole- 5-carboxamide
196		N-(1-(7-chloro-1,2,3,4- tetrahydronaphthalen-2- yl)-2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
197		N-((2S)-1,1- dicyclopropyl-3-oxo-3- ((2-((S)-2-oxo-4- (trifluoromethyl) imidazolidin-1-yl)-2,3- dihydro-1H-inden-5- yl)amino)propan-2-yl)- 1-methyl-1H-pyrazole- 5-carboxamide
198		N-((2S)-1,1- dicyclopropyl-3-oxo-3- ((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2-(7- (trifluoromethyl)-1H- benzo[d]imidazol-2-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)propan-2- yl)-1-isopropyl-1H- pyrazole-5-carboxamide
199		N-((1S)-1-cyclohexyl- 2-oxo-2-((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5- yl)amino)ethyl)-1- methyl-1H-pyrazole-5- carboxamide
200		N-((1S)-1-cyclohexyl- 2-((2-((3- fluorophenyl)carbamoyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
201		N-(1-(5-chloro-1,2,3,4- tetrahydronaphthalen-2- yl)-2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
202		N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (2-oxo-4- (trifluoromethyl) imidazolidin-1-yl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide
203		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-((3- fluorophenyl) carbamoyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
204		N-((2S)-3-(4- chlorophenyl)-1-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- oxopropan-2-yl)-1- methyl-1H-pyrazole-5- carboxamide
205		N-((1S)-1-(4,4- difluorocyclohexyl)-2- oxo-2-((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2-(4-phenyl-1H- imidazol-2-yl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
206		N-((2S)-1,1- dicyclopropyl-3-oxo-3- ((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2-(5-phenyl-1H- imidazol-2-yl)-2,3- dihydro-1H-inden-5- yl)amino)propan-2-yl)- 1-isopropyl-1H- pyrazole-5-carboxamide
207		pentan-3-yl 5-((S)-2- (4,4- difluorocyclohexyl)-2- (4-methyl-1,2,5- oxadiazole-3- carboxamido) acetamido)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- indene-2-carboxylate
208		N-(1-(6-chloro-1,2,3,4- tetrahydronaphthalen-2- yl)-2-oxo-2-((2-((S)-2- oxo-4- (trifluoromethyl) imidazolidin- 1-yl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
209		N-((1S)-1-cyclohexyl- 2-((2-((5S)-5-isopropyl- 2-oxopyrrolidin-3-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide
210		N-((1S)-2-((2-cyano-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-1- (4,4- difluorocyclohexyl)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
211		N-((2S)-1,1- dicyclopropyl-3-((2- ((5S)-5-isopropyl-2- oxopyrrolidin-3-yl)-2,3- dihydro-1H-inden-5- yl)amino)-3-oxopropan- 2-yl)-4-methyl-1,2,5- oxadiazole-3- carboxamide
213		N-((1S)-1-cyclohexyl- 2-oxo-2-((2-((S)-2-oxo- 4- (trifluoromethyl) imidazolidin-1-yl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
214		N-((1S)-1-(4,4- difluorocyclohexyl)-2- oxo-2-((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2-(o- tolylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
215		N-((1S)-1-(4,4- difluorocyclohexyl)-2- oxo-2-((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2-(thiazol-5- ylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
216		N-((2S)-1,1- dicyclopropyl-3-((2-((3- fluorophenyl)carbamoyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
217		N-(1-(6-chloro-1,2,3,4- tetrahydronaphthalen-2- yl)-2-oxo-2-((2-((S)-2- oxo-4- (trifluoromethyl) imidazolidin-1-yl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-1- methyl-1H-pyrazole-5- carboxamide
218		N-((2S)-1,1- dicyclopropyl-3-oxo-3- ((2-((S)-2-oxo-4- (trifluoromethyl) imidazolidin-1-yl)-2,3- dihydro-1H-inden-5- yl)amino)propan-2-yl)- 3-methylisoxazole-4- carboxamide
219		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-((5-fluoro-2- methylphenyl)carbamoyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
220		N-((1S)-2-((2-((3- chlorophenyl)carbamoyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-1- (4,4- difluorocyclohexyl)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
221		N-((1S)-1-(4,4- difluorocyclohexyl)-2- oxo-2-((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2-(p- tolylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
222		N-((2S)-1,1- dicyclopropyl-3-((2- (imidazo[1,2-a]pyridin- 2-yl)-2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
223		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-(imidazo[1,2- a]pyridin-2-yl)-2-(6- oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
224		N-(1-(7′-chloro-3′,4′- dihydro-2′H- spiro[cyclopropane-1,1′- naphthalen]-3′-yl)-2- oxo-2-((2-((S)-2-oxo-4- (trifluoromethyl) imidazolidin- 1-yl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-1- methyl-1H-pyrazole-5- carboxamide
225		N-((2S)-1,1- dicyclopropyl-3-((2- (methoxymethyl)-2-(2- oxo-4- (trifluoromethyl) imidazolidin- 1-yl)-2,3- dihydro-1H-inden-5- yl)amino)-3-oxopropan- 2-yl)-4-methyl-1,2,5- oxadiazole-3- carboxamide
226		N-((2S)-1-((2-cyano-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-3,3- dicyclopropyl-1- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
227		N-(1-(7′-chloro-3′,4′- dihydro-2′H- spiro[cyclopropane-1,1′- naphthalen]-3′-yl)-2- oxo-2-((2-((S)-2-oxo-4- (trifluoromethyl) imidazolidin- 1-yl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
228		N-((1S)-1-(4,4- difluorocyclohexyl)-2- oxo-2-((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2-((pyridazin-3- ylmethyl)carbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
229		N-((1S)-1-(4,4- difluorocyclohexyl)-2- oxo-2-((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2-(m- tolylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
230		N-((2S)-1-((2- cyclopentyl-2-(6-oxo- 5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-3,3- dicyclopropyl-1- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
231		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
232		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-((1-(2- fluorophenyl)cyclopropyl) carbamoyl)-2-(6- oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
233		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-((1-(2,5- difluorophenyl) cyclopropyl) carbamoyl)-2-(6- oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
234		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(phenylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
235		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(phenylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-1- isopropyl-1H-pyrazole- 5-carboxamide
236		N-((2S)-1,1- dicyclopropyl-3-((2-((3- fluorophenyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
237		N-((1S)-1-cyclohexyl- 2-oxo-2-((2-(((S)-2- oxo-4- (trifluoromethyl) imidazolidin-1-yl) methyl)-2,3- dihydrobenzofuran-6- yl)amino)ethyl)-1- methyl-1H-pyrazole-5- carboxamide
239		N-((2S)-1,1- dicyclopropyl-3-oxo-3- ((2-((S)-2-oxo-4- (trifluoromethyl) imidazolidin-1-yl)-2,3- dihydro-1H-inden-5- yl)amino)propan-2-yl)- 4-methylisoxazole-3- carboxamide
240		N-((S)-1-cyclohexyl-2- oxo-2-((2-(((S)-2-oxo- 4- (trifluoromethyl) imidazolidin-1- yl)methyl)benzofuran- 5-yl)amino)ethyl)-1- methyl-1H-pyrazole-5- carboxamide
241		N-((2S)-1,1- dicyclopropyl-3-((2-(4- fluorobenzyl)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
242		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(phenylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
243		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-((3- fluorophenyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
244		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methoxymethyl)-2,3- dihydro-1H-inden-5- yl)amino)-3-oxopropan- 2-yl)-4-methyl-1,2,5- oxadiazole-3- carboxamide
245		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methoxymethyl)-2,3- dihydro-1H-inden-5- yl)amino)-3-oxopropan- 2-yl)-1-methyl-1H- pyrazole-5-carboxamide
246		N-((2S)-1,1- dicyclopropyl-3-((2- (imidazo[1,2- b]pyridazin-2-yl)-2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
247		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-(2-hydroxypropan- 2-yl)-2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
248		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
249		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-((2- fluorophenyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
250		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(1,1,1-trifluoro-2- hydroxypropan-2-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
251		N-((2S)-1,1- dicyclopropyl-3-((2-(4- fluorophenyl)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
252		N-((2S)-1,1- dicyclopropyl-3-((2-(2- cyclopropyl-1H- imidazol-4-yl)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
253		N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(o-tolylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide
254		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-((2- methoxyphenyl) carbamoyl)- 2,3-dihydro-1H- inden-5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
255		N-((2S)-1,1- dicyclopropyl-3-oxo-3- ((2-(((S)-2-oxo-4- (trifluoromethyl) imidazolidin- 1-yl)methyl)-2,3- dihydrobenzofuran-6- yl)amino)propan-2-yl)- 4-methyl-1,2,5- oxadiazole-3- carboxamide
257		N-((1S)-1-(4,4- difluorocyclohexyl)-2- oxo-2-((2-(((S)-2-oxo- 4- (trifluoromethyl) imidazolidin-1- yl)methyl)-2,3- dihydrobenzofuran-6- yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
258		N-((1S)-1-(4,4- difluorocyclohexyl)-2- oxo-2-((2-(((S)-2-oxo- 4- (trifluoromethyl) imidazolidin-1- yl)methyl)-2,3- dihydrobenzofuran-6- yl)amino)ethyl)-1- methyl-1H-pyrazole-5- carboxamide
259		N-((2S)-1-((2-((3- chlorophenyl) carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3,3- dicyclopropyl-1- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
260		N-((2S)-1-((2-((3- chloro-4- (trifluoromethyl)phenyl) carbamoyl)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3,3- dicyclopropyl-1- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
262		N-((2S)-1,1- dicyclopropyl-3-((2-((2- fluorophenyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
263		N-((2S)-1-((2-((2- chlorophenyl) carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3,3- dicyclopropyl-1- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
264		N-((2S)-1,1- dicyclopropyl-3-((2- ((2,4- dichlorophenyl) carbamoyl)- 2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2,3-dihydro-1H- inden-5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
265		N-((2S)-1,1- dicyclopropyl-3-((2- ((3,5- dichlorophenyl) carbamoyl)- 2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2,3-dihydro-1H- inden-5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
266		N-((2S)-1-((2-cyano-2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3,3- dicyclopropyl-1- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
267		N-((2S)-1-((2-((2- chloro-4- cyclopropylphenyl) carbamoyl)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3,3- dicyclopropyl-1- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
268		N-((2S)-1,1- dicyclopropyl-3-((2-((2- (difluoromethyl)phenyl) carbamoyl)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
269		N-((2S)-1-((2-((4- chlorophenyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3,3- dicyclopropyl-1- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
270		N-((2S)-1,1- dicyclopropyl-3-oxo-3- ((2-(2-oxo-4- (trifluoromethyl) imidazolidin- 1-yl)-2-(2,2,2- trifluoro-1- hydroxyethyl)-2,3- dihydro-1H-inden-5- yl)amino)propan-2-yl)- 4-methyl-1,2,5- oxadiazole-3- carboxamide
271		N-((2S)-1,1- dicyclopropyl-3-((2- (((R)-4-isopropyl-2- oxoimidazolidin-1- yl)methyl)-2,3- dihydrobenzofuran-6- yl)amino)-3-oxopropan- 2-yl)-4-methyl-1,2,5- oxadiazole-3- carboxamide
272		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-((2- (trifluoromethyl)phenyl) carbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-3-oxopropan- 2-yl)-4-methyl-1,2,5- oxadiazole-3- carboxamide
273		N-((2S)-1,1- dicyclopropyl-3-((2- ((2,2- difluorocyclopropyl) carbamoyl)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
274		N-((2S)-1-((2-((4- chloropyridin-3- yl)carbamoyl)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3,3- dicyclopropyl-1- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
275		N-((2S)-1-((2-((2- chloro-6- fluorophenyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3,3- dicyclopropyl-1- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
276		N-((2S)-1,1- dicyclopropyl-3-oxo-3- ((2-(1-((S)-2-oxo-4- (trifluoromethyl) imidazolidin-1-yl) ethyl)-2,3- dihydrobenzofuran-6- yl)amino)propan-2-yl)- 4-methyl-1,2,5- oxadiazole-3- carboxamide
277		N-((2S)-1,1- dicyclopropyl-3-oxo-3- ((2-(1-((S)-2-oxo-4- (trifluoromethyl) imidazolidin- 1-yl)ethyl)-2,3- dihydrobenzofuran-6- yl)amino)propan-2-yl)- 1-isopropyl-1H- pyrazole-5-carboxamide
278		N-((2S)-1-((2-((2- chloro-5- fluorophenyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3,3- dicyclopropyl-1- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
280		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-((tetrahydrofuran-3- yl)carbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-3-oxopropan- 2-yl)-4-methyl-1,2,5- oxadiazole-3- carboxamide
281		N-((2S)-1,1- dicyclopropyl-3-((2- ((dicyclopropylmethyl) carbamoyl)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
282		N-((2S)-1-((2- (cyclopentylcarbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3,3- dicyclopropyl-1- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
283		N-((2S)-1-((2-((2- cyanophenyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3,3- dicyclopropyl-1- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
284		N-((2S)-1-((2-((3- chloropyridin-4- yl)carbamoyl)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3,3- dicyclopropyl-1- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
285		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(thiazol-5- ylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-3-oxopropan- 2-yl)-4-methyl-1,2,5- oxadiazole-3- carboxamide
286		N-((2S)-1,1- dicyclopropyl-3-((2- (((R)-4-isopropyl-2- oxoimidazolidin-1- yl)methyl)indolin-6- yl)amino)-3-oxopropan- 2-yl)-1-isopropyl-1H- pyrazole-5-carboxamide
287		N-((2S)-1,1- dicyclopropyl-3-((2- (((R)-4-isopropyl-2- oxoimidazolidin-1- yl)methyl)-1- methylindolin-6- yl)amino)-3-oxopropan- 2-yl)-1-isopropyl-1H- pyrazole-5-carboxamide
288		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-((2- isopropylphenyl) carbamoyl)-2, 3-dihydro-1H- inden-5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
289		N-((2S)-1,1- dicyclopropyl-3-((2-((2- ethylphenyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
290		N-((S)-1,1- dicyclopropyl-3-((2- (cyclopropyl((S)-2-oxo- 4- (trifluoromethyl) imidazolidin- 1-yl)-13-methyl)- 2,3-dihydro-213- benzofuran-6- yl)amino)-3-oxopropan- 2-yl)-1-isopropyl-1H- pyrazole-5-carboxamide
291		N-((1S)-1-cyclohexyl- 2-oxo-2-((3-(((S)-2- oxo-4- (trifluoromethyl) imidazolidin-1- yl)methyl)chroman-7- yl)amino)ethyl)-1- methyl-1H-pyrazole-5- carboxamide
292		N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(2,2,2-trifluoro-1- (methylamino)ethyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide
293		N-((2S)-1,1- dicyclopropyl-3-oxo-3- ((2-(((S)-2-oxo-4- (trifluoromethyl) imidazolidin- 1-yl)methyl)-2,3- dihydrobenzofuran-5- yl)amino)propan-2-yl)- 4-methyl-1,2,5- oxadiazole-3- carboxamide
	Ex.	Data
	1	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 8.45 (d, J = 8.4 Hz, 1H), 7.54-7.25 (m,
		4H), 7.10-7.05 (m, 1H), 7.01 (d, J = 1.6 Hz,
		1H), 6.57 (s, 1H), 4.33 (t, J = 8.4 Hz, 1H), 3.98
		(s, 3H), 3.55-3.36 (m, 4H), 3.33-3.05 (m, 2H),
		2.76-2.69 (m, 1H), 2.54 (d, J = 4.0 Hz, 3H),
		(s, 3H), 3.55-3.36 (m, 4H), 3.33-3.05 (m, 2H),
		2.76-2.69 (m, 1H), 2.54 (d, J = 4.0 Hz, 3H),
		1.85-1.50 (m, 6H), 1.21-1.10 (m, 5H), 1.03-
		0.95 (m, 3H). MS (ESI, m/e) [M + 1]+ 536.5.
	2	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.05
		(s, 1H), 8.44 (d, J = 8.4 Hz, 1H), 7.49-7.28 (m,
		3H), 7.09-7.04 (m, 1H), 7.02 (d, J = 2.0 Hz,
		1H), 6.35 (s, 1H), 4.33 (t, J = 8.4 Hz, 1H), 3.98
		(s, 3H), 3.59-3.44 (m, 4H), 3.33-3.15 (m, 5H),
		3.06-2.95 (m, 3H), 1.85-1.50 (m, 6H), 1.21-
		1.10 (m, 5H), 1.01 (d, J = 6.0 Hz, 3H). MS
		(ESI, m/e) [M + 1]+ 523.3.
	3	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 8.45 (d, J = 8.0 Hz, 1H), 7.59-7.28 (m,
		3H), 7.11 (d, J = 8.0 Hz, 1H), 7.02 (d, J = 2.0
		Hz, 1H), 6.43 (s, 1H), 4.59-4.50 (m, 1H), 4.33
		(t, J = 8.4 Hz, 1H), 3.98 (s, 3H), 3.57-3.47 (m,
		1H), 3.33-3.15 (m, 2H), 3.06-2.85 (m, 2H),
		2.84-2.70 (m, 2H), 2.64-2.55 (m, 1H), 1.85-
		1.50 (m, 6H), 1.21-1.10 (m, 4H), 1.03-0.95 (m,
		3H). MS (ESI, m/e) [M + 1]+ 479.2.
	4	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.04
		(s, 1H), 8.42 (d, J = 8.0 Hz, 1H), 7.85-7.82 (m,
		1H), 7.48 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 4.0
		Hz, 1H), 7.30-7.26 (m, 1H), 7.06 (d, J = 8.0
		Hz, 1H), 7.02 (d, J = 4.0 Hz, 1H), 4.35-4.31
		(m, 1H), 3.98 (s, 3H), 3.27 (s, 1H), 3.13-3.05
		(m, 1H), 2.97-2.91 (m, 4H), 2.56 (d, J = 8.0
		Hz, 1H), 1.79-1.77 (m, 2H), 1.68-1.65 (m,
		2H), 1.58-1.51 (m, 2H), 1.19-1.11 (m, 4H).
		MS (ESI, m/e) [M + 1]+ 438.1.
	5	1H NMR (400 MHz, DMSO-d6) δ ppm: 12.23
		(br, 1H), 8.74 (d, J = 8.8 Hz, 1H), 7.50-7.45
		(m, 1H), 7.42 (d, J = 2.0 Hz, 1H), 7.30-7.20
		(m, 2H), 7.02 (d, J = 1.6 Hz, 1H), 6.52 (s, 1H),
		4.97 (t, J = 8.8 Hz, 1H), 3.97 (s, 3H), 3.59-3.40
		(m, 4H), 3.32-3.15 (m, 2H), 2.73 (t, J = 7.6 Hz,
		1H), 2.54 (d, J = 4.4 Hz, 3H), 2.11-2.00 (m,
		1H), 1.85-1.78 (m, 1H), 1.72-1.52 (m, 3H),
		1.38-1.30 (m, 1H), 1.21-0.95 (m, 9H). MS
		(ESI, m/e) [M + 1]+ 533.5.
	6	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 8.46 (d, J = 8.2 Hz, 1H), 7.58 (d, J =
		4.4 Hz, 1H), 7.41 (d, J = 2.0 Hz, 1H), 7.31 (s,
		1H), 7.11-7.00 (m, 2H), 6.84 (d, J = 8.8 Hz,
		1H), 6.60 (s, 1H), 4.50-4.25 (m, 5H), 3.98 (s,
		3H), 3.74-3.63 (m, 2H), 3.27 (s, 3H), 3.18-3.12
		(m, 1H), 2.55-2.53 (m, 3H), 1.78-1.75 (m, 2H),
		1.65-1.54 (m, 4H), 1.20-1.05 (m, 6H). MS
		(ESI, m/e) [M + 1]+ 568.3.
	7	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.01
		(s, 1H), 8.42 (d, J = 8.4 Hz, 1H), 7.42 (d, J =
		1.6 Hz, 1H), 7.39-7.27 (m, 3H), 7.04-6.97 (m,
		2H), 6.40 (s, 1H), 4.32 (t, J = 8.8 Hz, 1H), 4.03
		(s, 3H), 3.60-3.40 (m, 2H), 2.95- 2.50 (m, 8H),
		2.38-2.20 (m, 1H), 1.90-1.50 (m, 8H), 1.21-
		1.10 (m, 6H), 1.07-0.95 (m, 3H). MS (ESI,
		m/e) [M + 1]+ 564.3.
	8	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.21
		(s, 1H), 8.50 (d, J = 8.0 Hz, 1H), 7.80-7.76 (m,
		1H), 7.57-7.28 (m, 4H), 7.06 (d, J = 2.0 Hz,
		1H), 6.74 (d, J = 27.6 Hz, 1H), 4.37 (t, J = 8.4
		Hz, 1H), 4.02 (s, 3H), 3.69-3.45 (m, 1H), 3.30-
		2.72 (m, 5H), 2.55 (t, J = 4.8 Hz, 3H), 2.30-
		1.91 (m, 2H), 1.90-1.55 (m, 6H), 1.21-1.10 (m,
		5H), 1.07-0.95 (m, 3H). MS (ESI, m/e) [M + 1]+
		536.3.
	9	MS (ESI) m/e [M + 1]+ 542.2
	10	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.06
		(s, 1H), 8.47 (d, J = 8.0 Hz, 1H), 7.45-7.41 (m,
		2H), 7.37-7.35 (m, 1H), 7.28-7.25 (m, 1H),
		7.02-7.01 (m, 1H), 6.94 (d, J = 8.0 Hz, 1H),
		6.38 (s, 1H), 4.36-4.31 (m, 1H), 3.46-3.41 (m,
		1H), 3.24-3.18 (m, 2H), 3.08-2.83 (m, 5H),
		2.56-2.53 (m, 5H), 1.98-1.92 (m, 1H), 1.79-
		1.77 (m, 2H), 1.68-1.66 (m, 2H), 1.58-1.52 (m,
		2H), 1.19-1.11 (m, 4H), 1.01-0.99 (m, 4H).
		MS (ESI, m/e) [M + 1]+ 550.3.
	11	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.23
		(s, 1H), 8.51 (d, J = 8.2 Hz, 1H), 7.99-7.94 (m,
		1H), 7.52-7.36 (m, 3H), 7.10-7.03 (m, 1H),
		6.75 (s, 1H), 6.69 (s, 1H), 4.47-4.29 (m, 3H),
		4.03 (s, 3H), 3.70-3.59 (m, 1H), 3.48-3.40 (m,
		1H), 2.89-2.78 (m, 1H), 1.95-1.77 (m, 2H),
		1.77-1.55 (m, 4H), 1.30-1.22 (m, 5H), 1.12-
		1.05 (m, 3H). MS (ESI, m/e) [M + 1]+ 493.3
	12	1H NMR (400 MHz, DMSO-d6) δ ppm: 7.71
		(s, 1H), 7.47 (s, 1H), 7.28 (d, J = 8.8 Hz, 1H),
		7.18 (d, J = 8.8 Hz, 1H), 6.90 (d, J = 1.6 Hz,
		1H), 6.31 (s, 1H), 4.48-4.41 (m, 2H), 4.09 (s,
		3H), 3.79-3.75 (m, 1H), 3.52-3.47 (m, 1H),
		3.00-2.88 (m, 1H), 1.94-1.72 (m, 5H), 1.41-
		1.32 (m, 6H), 1.18 (d, J = 6.2 Hz, 4H). MS
		(ESI, m/e) [M + 1]+ 492.2.
	13	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.12
		(s, 1H), 8.49 (d, J = 8.0 Hz, 1H), 7.64-7.30 (m,
		4H), 7.14-6.95 (m, 2H), 6.46 (s, 1H), 4.37 (t,
		J = 8.4 Hz, 1H), 4.02 (s, 3H), 3.50-3.40 (m, 2H),
		3.33-3.09 (m, 6H), 2.58 (d, J = 4.4 Hz, 3H),
		1.90-1.55 (m, 6H), 1.21-0.95 (m, 5H). MS
		(ESI, m/e) [M + 1]+ 522.4.
	14	1H NMR (400 MHz, DMSO-d6) δ ppm: 12.20
		(d, J = 18.0 Hz, 1H), 9.40 (t, J = 6.4 Hz, 1H),
		7.55-7.48 (m, 1H), 7.35 (d, J = 3.2 Hz, 1H),
		7.27 (d, J = 4.0 Hz, 1H), 6.57 (s, 1H), 5.05 (t,
		J = 8.0 Hz, 1H), 3.65-3.40 (m, 4H), 3.32-3.20
		(m, 2H), 2.83-2.69 (m, 1H), 2.58 (d, J = 4.4
		Hz, 3H), 2.11-1.96 (m, 2H), 1.90-1.55 (m,
		4H), 1.21-0.95 (m, 8H). MS (ESI, m/e) [M + 1]+
		535.4.
	15	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.12
		(s, 1H), 8.49 (d, J = 8.4 Hz, 1H), 7.57-7.30 (m,
		3H), 7.14-6.95 (m, 4H), 6.63 (s, 1H), 4.38 (t,
		J = 8.8 Hz, 1H), 4.03 (s, 3H), 3.60-3.40 (m, 4H),
		3.33-3.09 (m, 2H), 2.83-2.75 (m, 1H), 1.90-
		1.55 (m, 6H), 1.21-1.10 (m, 5H), 1.07-0.95 (m,
		3H). MS (ESI, m/e) [M + 1]+ 522.2.
	16	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.03
		(s, 1H), 8.58 (d, J = 8.0 Hz, 1H), 7.59-7.22 (m,
		3H), 7.14-7.05 (m, 2H), 6.61 (s, 1H), 4.63-4.40
		(m, 1H), 4.03 (s, 3H), 3.63-3.40 (m, 4H), 3.33-
		3.05 (m, 2H), 2.87-2.69 (m, 1H), 2.58 (d, J =
		4.4 Hz, 3H), 2.05-2.00 (m, 2H), 1.90-1.55 (m,
		6H), 1.21-1.10 (m, 5H), 1.07-0.95 (m, 3H),
		0.93-0.85 (m, 2H). MS (ESI, m/e) [M + 1]+
		550.2.
	17	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 8.48 (d, J = 8.0 Hz, 1H), 7.77-7.30 (m,
		4H), 7.14-7.05 (m, 2H), 6.48 (s, 1H), 4.38 (t, J =
		8.0 Hz, 1H), 4.02 (s, 3H), 3.93-3.78 (m, 1H),
		3.76-3.68 (m, 1H), 3.63-3.40 (m, 3H), 3.33-
		3.05 (m, 1H), 2.88-2.76 (m, 1H), 2.58 (d, J =
		4.4 Hz, 3H), 1.90-1.55 (m, 6H), 1.21-1.10 (m,
		5H), 1.07-0.95 (m, 3H). MS (ESI, m/e) [M + 1]+
		536.3
	18	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 8.49 (d, J = 8.0 Hz, 1H), 7.58-7.29 (m,
		4H), 7.12 (d, J = 7.6 Hz, 1H), 7.10 (s, 1H),
		6.74 (s, 1H), 4.37 (t, J = 8.4 Hz, 1H), 4.02 (s,
		3H), 3.55-3.35 (m, 4H), 3.33-3.11 (m, 2H),
		2.90-2.83 (m, 1H), 2.58 (d, J = 4.4 Hz, 3H),
		1.90-1.54 (m, 6H), 1.38-1.30 (m, 2H), 1.20-
		0.95 (m, 5H), 0.74 (t, J = 7.2 Hz, 1H). MS
		(ESI, m/e) [M + 1]+ 550.4.
	19	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.48 (d, J = 8.4 Hz, 1H), 7.58-7.29 (m,
		4H), 7.13-7.05 (m, 2H), 6.73 (s, 1H), 4.37 (t,
		J = 8.8 Hz, 1H), 4.02 (s, 3H), 3.55-3.35 (m, 4H),
		3.33-3.11 (m, 2H), 2.85 (t, J = 7.2 Hz, 1H),
		2.58 (d, J = 4.4 Hz, 3H), 1.90-1.54 (m, 6H),
		1.38-1.30 (m, 2H), 1.20-0.95 (m, 5H), 0.74 (t,
		J = 7.2 Hz, 3H). MS (ESI, m/e) [M + 1]+ 550.4.
	20	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.48 (d, J = 8.4 Hz, 1H), 7.60-7.28 (m,
		4H), 7.12 (d, J = 8.0 Hz, 1H), 7.06 (s, 1H),
		6.62 (s, 1H), 4.37 (t, J = 8.4 Hz, 1H), 4.02 (s,
		3H), 3.49-3.42 (m, 2H), 3.24-3.00 (m, 4H),
		2.58 (d, J = 4.4 Hz, 3H), 1.90-1.57 (m, 6H),
		1.20-1.10 (m, 5H), 1.07-0.95 (m, 3H). MS
		(ESI, m/e) [M + 1]+ 550.4.
	21	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.12
		(d, J = 3.2 Hz, 1H), 8.48 (d, J = 8.2 Hz, 1H),
		7.46 (d, J = 1.6 Hz, 1H), 7.27-7.16 (m, 1H),
		7.14-7.05 (m, 2H), 7.05-6.91 (m, 1H), 6.50 (d,
		J = 18.4 Hz, 1H), 4.96-4.83 (m, 1H), 4.42-4.32
		(m, 1H), 4.03 (s, 3H), 3.64-3.45 (m, 2H), 3.30-
		3.11 (m, 3H), 3.03-2.80 (m, 2H), 1.91-1.47 (m,
		6H), 1.21-1.05 (m, 5H), 1.05-0.95 (m, 1H),
		0.93-0.85 (m, 2H). MS (ESI, m/e) [M + 1]+.
		495.3.
	22	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.08
		(s, 1H), 8.48 (d, J = 8.0 Hz, 1H), 7.57-7.30 (m,
		3H), 7.14-7.05 (m, 2H), 6.37 (s, 1H), 4.99 (t, J =
		5.2 Hz, 1H), 4.38 (t, J = 8.0 Hz, 1H), 4.02 (s,
		3H), 3.63-3.40 (m, 3H), 3.33-3.05 (m, 6H),
		1.90-1.55 (m, 6H), 1.21-1.10 (m, 5H), 1.07-
		0.95 (m, 3H). MS (ESI, m/e) [M + 1]+ 509.3.
	23	1H NMR (400 MHz, DMSO-d6) δ ppm: 12.46
		(br, 1H), 10.12 (s, 1H), 8.49 (d, J = 8.0 Hz,
		1H), 7.57-7.30 (m, 3H), 7.14-7.05 (m, 2H),
		6.61 (s, 1H), 4.38 (t, J = 8.0 Hz, 1H), 3.92 (s,
		3H), 3.63-3.40 (m, 4H), 3.33-3.05 (m, 2H),
		3.00-2.88 (m, 1H), 1.90-1.55 (m, 6H), 1.21-
		1.10 (m, 5H), 1.07-0.95 (m, 3H). MS (ESI,
		m/e) [M + 1]+ 523.3.
	24	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.48 (d, J = 8.0 Hz, 1H), 7.57-7.25 (m,
		4H), 7.14-7.05 (m, 2H), 6.70 (s, 1H), 4.35 (t, J =
		7.6 Hz, 1H), 4.02 (s, 3H), 3.63-3.40 (m, 3H),
		3.33-3.05 (m, 3H), 2.75-2.68 (m, 1H), 2.58 (d,
		J = 4.4 Hz, 3H), 1.90-1.55 (m, 6H), 1.21-1.10
		(m, 5H), 1.07-0.95 (m, 9H). MS (ESI, m/e)
		[M + 1]+ 578.4.
	25	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 8.46 (d, J = 8.2 Hz, 1H), 7.53 (s, 2H),
		7.46 (d, J = 2.0 Hz, 1H), 7.39-7.31 (m, 1H),
		7.14-7.09 (m, 1H), 7.06 (s, 1H), 6.76-6.70 (m,
		1H), 4.41-4.33 (m, 1H), 4.02 (s, 3H), 3.58-3.35
		(s, 2H), 3.22-3.16 (m, 1H), 3.05-2.94 (m, 4H),
		2.57 (d, J = 4.4 Hz, 3H), 1.86-1.77 (m, 2H),
		1.31-0.93 (m, 20H). MS (ESI, m/e) [M + 1]+
		604.4.
	26	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.47 (d, J = 8.2 Hz, 1H), 7.57-7.48 (m,
		2H), 7.46 (d, J = 2.0 Hz, 1H), 7.42-7.30 (m,
		1H), 7.15-7.08 (m, 1H), 7.08-7.04 (m, 1H),
		6.71 (s, 1H), 4.42-4.30 (m, 1H), 4.02 (s, 3H),
		3.54-3.35 (m, 5H), 3.29-3.09 (m, 2H), 2.90-
		2.76 (m, 1H), 2.57 (d, J = 4.4 Hz, 3H), 2.03 -
		1.52 (m, 7H), 1.35-1.27 (m, 2H), 1.20-1.07 (s,
		5H), 0.84-0.77 (m, 3H). MS (ESI, m/e)
		[M + 1]+. 564.4.
	27	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.48 (d, J = 8.4 Hz. 1H), 7.49-7.42 (m,
		4H), 7.08-7.02 (m, 2H), 6.76 (s, 1H), 4.39-4.36
		(m, 1H), 4.02 (s, 3H), 3.46-3.41 (m, 3H), 3.21-
		3.01 (m, 2H), 2.54-2.51 (m, 3H), 2.24-2.21 (m,
		1H),1.81-1.57 (m, 13H), 1.05-1.02 (m, 4H).
		MS (ESI, m/e) [M + 1]+ 576.4.
	28	1H NMR (400 MHz, DMSO-d6) δ ppm: 12.18
		(br, 1H), 8.79 (s, 1H), 7.55-7.20 (m, 4H), 7.07
		(s, 1H), 6.73 (s, 1H), 5.02 (t, J = 5.6 Hz, 1H),
		4.02 (s, 3H), 3.64-3.40 (m, 4H), 3.32-3.14 (m,
		2H), 2.97-2.89 (m, 1H), 2.58 (d, J = 4.4 Hz,
		3H), 2.15-1.95 (m, 2H), 1.90-1.35 (m, 6H),
		1.21-0.95 (m, 5H), 0.71 (d, J = 6.8 Hz, 3H),
		0.66 (d, J = 6.8 Hz, 3H). MS (ESI, m/e)
		[M + 1]+ 561.3.
	29	1H NMR (400 MHz, DMSO-d6) δ ppm: 12.18
		(br, 1H), 9.41 (d, J = 9.2 Hz, 1H), 7.59-7.20
		(m, 3H), 6.73 (s, 1H), 5.06 (t, J = 8.0 Hz, 1H),
		3.67-3.40 (m, 4H), 3.32-3.14 (m, 2H), 2.97-
		2.89 (m, 1H), 2.58 (d, J = 4.4 Hz, 3H), 2.11-
		1.95 (m, 2H), 1.90-1.39 (m, 6H), 1.21-0.95 (m,
		4H), 0.71 (d, J = 6.8 Hz, 3H), 0.66 (d, J = 6.8
		Hz, 3H). MS (ESI, m/e) [M + 1]+ 563.3.
	30	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.14
		(s, 1H), 9.09 (d, J = 8.0 Hz, 1H), 7.59-7.29 (m,
		3H), 7.13 (d, J = 8.4 Hz, 1H), 6.78 (s, 1H),
		4.45 (t, J = 8.0 Hz, 1H), 3.59-3.46 (m, 2H),
		3.32-3.10 (m, 4H), 2.93-2.87 (m, 1H), 2.58 (d,
		J = 4.4 Hz, 3H), 1.90-1.39 (m, 7H), 1.21-0.95
		(m, 5H), 0.75 (d, J = 6.8 Hz, 3H), 0.70 (d, J =
		6.4 Hz, 3H). MS (ESI, m/e) [M + 1]+ 566.3.
	31	1H NMR (400 MHz, DMSO-d6) δ ppm: 12.20
		(br, 1H), 8.78 (d, J = 8.0 Hz, 1H), 7.55-7.20
		(m, 4H), 7.07 (s, 1H), 6.69 (s, 1H), 5.01 (t, J =
		8.4 Hz, 1H), 4.02 (s, 3H), 3.65-3.40 (m, 4H),
		3.32-3.23 (m, 2H), 2.93-2.87 (m, 1H), 2.58 (d,
		J = 4.4 Hz, 3H), 2.10-1.55 (m, 5H), 1.42-1.27
		(m, 3H), 1.21-0.95 (m, 5H), 0.70 (t, J = 7.2 Hz,
		3H). MS (ESI, m/e) [M + 1]+ 547.3.
	33	1H NMR (400 MHz, DMSO-d6) δ ppm: 12.28
		(br, 1H), 9.42 (d, J = 8.8 Hz, 1H), 7.55-7.50
		(m, 1H), 7.32 (s, 2H), 6.69 (s, 1H), 5.06 (t, J =
		8.8 Hz, 1H), 3.62-3.40 (m, 4H), 3.32-3.23 (m,
		2H), 2.93-2.87 (m, 1H), 2.58 (d, J = 4.4 Hz,
		3H), 2.14-1.55 (m, 5H), 1.42-1.27 (m, 3H),
		1.21-0.95 (m, 5H), 0.71 (t, J = 7.2 Hz, 3H).
		MS (ESI, m/e) [M + 1]+ 549.4.
	34	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.53 (d, J = 8.4 Hz. 1H), 7.49-7.42 (m,
		4H), 7.08-7.02 (m, 2H), 6.76 (s, 1H), 4.39-4.36
		(m, 1H), 4.02 (s, 3H), 3.46-3.41 (m, 6H), 3.21-
		3.01 (m, 4H), 2.54-2.51 (m, 3H), 1.81-1.57 (m,
		7H), 1.31-1.17 (m, 5H), 1.05-1.02 (m, 2H).
		MS (ESI, m/e) [M + 1]+ 592.3.
	35	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.53 (d, J = 8.4 Hz. 1H), 7.49-7.42 (m,
		4H), 7.08-7.02 (m, 2H), 6.76 (s, 1H), 4.39-4.36
		(m, 1H), 4.02 (s, 3H), 3.46-3.41 (m, 3H), 3.21-
		3.01 (m, 10H), 2.54-2.51 (m, 3H), 1.81-1.57
		(m, 7H), 1.31-1.17 (m, 6H), 1.05-1.02 (m, 2H),
		0.63-0.55 (m, 2H). MS (ESI, m/e) [M + 1]+
		594.3.
	36	MS (ESI, m/e) [M + 1]+ 598.3.
	37	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.15
		(d, J = 20.0 Hz, 1H), 8.52-8.47 (m, 1H), 7.59-
		7.45 (m, 2H), 7.41-7.34 (m, 1H), 7.25-7.12 (m,
		4H), 7.09-7.02 (m, 3H), 6.93 (d, J = 8.0 Hz,
		1H), 6.74 (d, J = 4.0 Hz, 1H), 4.42-4.36 (m,
		1H), 4.02 (d, J = 8.0 Hz, 1H), 3.69-3.63 (m,
		1H), 3.50-3.41 (m, 2H), 3.31-3.27 (m, 2H),
		3.12-3.05 (m, 2H), 2.98-2.95 (m, 1H), 2.72-
		2.65 (m, 1H), 2.55-2.53 (m, 3H), 1.90-1.79 (m,
		2H), 1.75-1.54 (m, 4H), 1.35-1.10 (m, 8H),
		1.02-0.78 (m, 2H). MS (ESI, m/e) [M + 1]+.
	38	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.49 (d, J = 8.0 Hz, 1H), 7.57-7.29 (m,
		4H), 7.12 (d, J = 8.4 Hz, 1H), 7.06 (s, 1H),
		6.77 (s, 1H), 4.37 (t, J = 8.8 Hz, 1H), 4.02 (s,
		3H), 3.58-3.45 (m, 2H), 3.33-3.11 (m, 4H),
		2.94-2.87 (m, 1H), 2.58 (d, J = 4.4 Hz, 3H),
		1.90-1.54 (m, 6H), 1.48-1.40 (m, 2H), 1.20-
		0.95 (m, 5H),), 0.75 (d, J = 6.4 Hz, 3H), 0.70
		(d, J = 6.8 Hz, 3H). MS (ESI, m/e) [M + 1]+
		564.3.
	39	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.49 (d, J = 8.0 Hz, 1H), 7.59-7.29 (m,
		4H), 7.12 (d, J = 8.0 Hz, 1H), 7.06 (d, J = 2.0
		Hz, 1H), 6.77 (s, 1H), 4.37 (t, J = 8.4 Hz, 1H),
		4.02 (s, 3H), 3.57-3.45 (m, 2H), 3.32-3.10 (m,
		4H), 2.93-2.87 (m, 1H), 2.58 (d, J = 4.4 Hz,
		3H), 1.90-1.39 (m, 7H), 1.21-0.95 (m, 5H),
		0.74 (d, J = 6.8 Hz, 3H), 0.70 (d, J = 6.4 Hz,
		3H). MS (ESI, m/e) [M + 1]+ 564.3.
	40	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.15
		(s, 1H), 9.09 (d, J = 8.0 Hz, 1H), 7.55-7.27 (m,
		3H), 7.13 (d, J = 8.4 Hz, 1H), 6.78 (s, 1H),
		4.46 (t, J = 8.0 Hz, 1H), 3.57-3.45 (m, 2H),
		3.32-3.10 (m, 4H), 2.93-2.87 (m, 1H), 2.58 (d,
		J = 4.4 Hz, 3H), 1.90-1.39 (m, 7H), 1.21-1.00
		(m, 5H), 0.77-0.50 (m, 6H). MS (ESI, m/e)
		[M + 1]+ 566.5.
	41	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.12
		(s, 1H), 8.49 (d, J = 8.4 Hz, 1H), 7.58-7.27 (m,
		4H), 7.15-7.10 (m, 1H), 7.06 (d, J = 1.6 Hz,
		1H), 6.73 (s, 1H), 4.37 (t, J = 8.0 Hz, 1H), 4.02
		(s, 3H), 3.56-3.35 (m, 3H), 3.30-3.10 (m, 2H),
		3.04-2.89 (m, 2H), 2.58 (d, J = 4.4 Hz, 3H),
		1.90-1.55 (m, 6H), 1.20-0.78 (m, 5H), 0.38-
		0.28 (m, 2H), 0.15-0.09 (m, 2H). MS (ESI,
		m/e) [M + 1]+ 562.3.
	42	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.53 (d, J = 8.4 Hz. 1H), 7.49-7.22 (m,
		4H), 7.08-7.02 (m, 2H), 6.76 (s, 1H), 4.59-4.56
		(m, 1H), 4.39-4.35 (m, 1H), 4.03 (s, 3H), 3.46-
		3.41 (m, 3H), 3.21-3.01 (m, 2H), 2.54-2.51 (m,
		3H), 1.91-1.57 (m, 7H), 1.31-1.17 (m, 2H),
		1.05-1.02 (m, 2H), 0.87-0.81 (m, 7H). MS
		(ESI, m/e) [M + 1]+ 580.3.
	43	MS (ESI, m/e) [M + 1]+ 613.4.
	44	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(d, J = 4.0 Hz, 1H), 8.48 (d, J = 8.0 Hz, 1H),
		7.56-7.47 (m, 2H), 7.46 (d, J = 4.0 Hz, 1H),
		7.42-7.30 (m, 1H), 7.12-7.10 (m, 1H), 7.06 (d,
		J = 4.0 Hz, 1H), 6.79 (s, 1H), 4.40-4.35 (m,
		1H), 4.02 (s, 3H), 3.60-3.50 (m, 1H), 3.45-3.41
		(m, 1H), 3.30-3.28 (m, 1H), 3.24-3.10 (m, 2H),
		2.99-2.94 (m, 1H), 2.57 (d, J = 4.0 Hz, 3H),
		1.83-1.81 (m, 2H), 1.73-1.68 (m, 2H), 1.62-
		1.53 (m, 2H), 1.23-0.79 (m, 6H), 0.66 (s, 9H).
		MS (ESI, m/e) [M + 1]+ 578.4.
	45	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.06
		(s, 1H), 8.50 (d, J = 7.6 Hz, 1H), 7.58-7.27 (m,
		4H), 7.12 (d, J = 8.0 Hz, 1H), 7.03 (d, J = 1.6
		Hz, 1H), 6.77 (s, 1H), 4.54 (t, J = 9.6 Hz, 1H),
		4.03 (s, 3H), 3.57-3.45 (m, 2H), 3.32-3.10 (m,
		4H), 2.93-2.87 (m, 1H), 2.80-2.67 (m, 1H),
		2.58 (d, J = 4.4 Hz, 3H), 2.10-1.75 (m, 1H),
		1.50-1.40 (m, 1H), 0.72-0.66 (m, 6H). MS
		(ESI, m/e) [M + 1]+ 536.5.
	46	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 8.61 (d, J = 8.0 Hz, 1H), 7.58-7.30 (m,
		4H), 7.12 (d, J = 8.0 Hz, 1H), 7.05 (d, J = 1.6
		Hz, 1H), 6.77 (s, 1H), 4.37 (t, J = 9.2 Hz, 1H),
		4.03 (s, 3H), 3.57-3.45 (m, 2H), 3.32-3.12 (m,
		4H), 2.93-2.87 (m, 1H), 2.58 (d, J = 4.4 Hz,
		3H), 2.40-2.30 (m, 1H), 1.89-1.80 (m, 1H),
		1.70-1.28 (m, 9H), 0.75 (d, J = 6.4 Hz, 3H),
		0.70 (d, J = 6.8 Hz, 3H). MS (ESI, m/e)
		[M + 1]+ 550.5.
	47	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.50 (d, J = 8.8 Hz, 1H), 7.57-7.30 (m,
		4H), 7.12 (d, J = 8.0 Hz, 1H), 7.06 (d, J = 1.6
		Hz, 1H), 6.77 (s, 1H), 4.45 (t, J = 8.0 Hz, 1H),
		4.03 (s, 3H), 3.57-3.45 (m, 2H), 3.32-3.12 (m,
		4H), 2.93-2.87 (m, 1H), 2.58 (d, J = 4.4 Hz,
		3H), 2.13-2.04 (m, 1H), 1.78-1.28 (m, 14H),
		0.74 (d, J = 6.4 Hz, 3H), 0.70 (d, J = 6.4 Hz,
		3H). MS (ESI, m/e) [M + 1]+ 578.4.
	48	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.22-
		10.19 (m, 1H), 8.58-8.54 (m, 1H), 7.73-7.56
		(m, 1H), 7.54-7.50 (m, 1H), 7.47-7.40 (m, 1H),
		7.32-7.24 (m, 3H), 7.22-7.10 (m, 4H), 7.08-
		7.02 (m, 1H), 6.86-6.72 (m, 1H), 4.47-4.43 (m,
		1H), 4.10-4.07 (m, 3H), 3.17-3.02 (m, 3H),
		2.89-2.76 (m, 1H), 2.61-2.59 (m, 2H), 2.09-
		2.02 (m, 1H), 1.95-1.86 (m, 2H), 1.80-1.73 (m,
		2H), 1.71-1.62 (m, 2H), 1.42 (s, 1H), 1.30-1.20
		(m, 9H), 1.14-1.05 (m, 2H). MS (ESI, m/e)
		[M + 1]+ 626.4.
	49	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.00
		(s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 7.55-7.25 (m,
		3H), 7.11 (d, J = 8.4 Hz, 1H), 6.76 (s, 1H),
		4.29 (t, J = 8.0 Hz, 1H), 3.59-3.45 (m, 2H),
		3.32-3.10 (m, 4H), 2.94-2.87 (m, 1H), 2.58 (d,
		J = 4.4 Hz, 3H), 1.81-1.40 (m, 7H), 1.21-0.80
		(m, 7H), 0.74 (d, J = 6.8 Hz, 3H), 0.72-0.66
		(m, 6H). MS (ESI, m/e) [M + 1]+ 524.4.
	50	1H NMR (400 MHz, DMSO-d6) δ ppm: 9.94
		(s, 1H), 7.55-7.20 (m, 4H), 7.11 (d, J = 8.0 Hz,
		1H), 6.77 (s, 1H), 4.02-3.93 (m, 3H), 3.59-3.45
		(m, 2H), 3.32-3.10 (m, 4H), 2.94-2.87 (m, 1H),
		2.58 (d, J = 4.8 Hz, 3H), 1.78-1.40 (m, 7H),
		1.21-0.93 (m, 8H), 0.74 (d, J = 6.8 Hz, 3H),
		0.69 (d, J = 6.4 Hz, 3H). MS (ESI, m/e)
		[M + 1]+ 528.3.
	51	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.03
		(s, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.58-7.08 (m,
		9H), 6.77 (s, 1H), 4.03 (t, J = 8.4 Hz, 1H),
		3.59-3.45 (m, 2H), 3.32-3.10 (m, 4H), 2.94-
		2.87 (m, 1H), 2.58 (d, J = 4.8 Hz, 3H), 1.85-
		1.40 (m, 7H), 1.21-1.03 (m, 5H), 0.77-0.66 (m,
		6H). MS (ESI, m/e) [M + 1]+ 576.4.
	52	1H NMR (400 MHz, DMSO-d6) δ ppm: 9.98
		(s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.55-7.08 (m,
		9H), 6.76 (s, 1H), 4.27 (t, J = 8.0 Hz, 1H),
		3.59-3.45 (m, 2H), 3.32-3.10 (m, 4H), 2.94-
		2.87 (m, 1H), 2.84-2.78 (m, 2H), 2.58 (d, J =
		4.8 Hz, 3H), 2.48-2.38 (m, 2H), 1.70-1.40 (m,
		7H), 1.21-0.83 (m, 5H), 0.74 (d, J = 6.8 Hz,
		3H), 0.69 (d, J = 6.4 Hz, 3H). MS (ESI, m/e)
		[M + 1]+ 588.4.
	53	1H NMR (400 MHz, DMSO-d6) δ ppm: 9.99
		(s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 7.55-7.17 (m,
		8H), 7.11 (d, J = 8.4 Hz, 1H), 6.76 (s, 1H),
		4.28 (t, J = 8.0 Hz, 1H), 3.59-3.45 (m, 4H),
		3.32-3.10 (m, 4H), 2.94-2.86 (m, 1H), 2.58 (d,
		J = 4.8 Hz, 3H), 1.75-1.40 (m, 7H), 1.21-0.95
		(m, 5H), 0.77-0.66 (m, 6H). MS (ESI, m/e)
		[M + 1]+ 574.4.
	54	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.08
		(s, 1H), 8.46 (d, J = 8.0 Hz, 1H), 7.91 (d, J =
		7.2 Hz, 1H), 7.58-7.29 (m, 6H), 7.12 (d, J =
		8.4 Hz, 1H), 6.76 (s, 1H), 4.41 (t, J = 8.4 Hz,
		1H), 3.59-3.45 (m, 2H), 3.32-3.10 (m, 4H),
		2.90 (t, J = 8.0 Hz, 1H), 2.58 (d, J = 4.4 Hz,
		3H), 1.93-1.55 (m, 6H), 1.48-1.38 (m, 1H),
		1.21-0.95 (m, 5H), 0.76-0.66 (m, 6H). MS
		(ESI, m/e) [M + 1]+ 560.3.
	55	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.48 (d, J = 8.4 Hz, 1H), 7.77-7.72 (m,
		1H), 7.54-7.33 (m, 4H), 7.11 (d, J = 8.0 Hz,
		1H), 7.06 (d, J = 2.0 Hz, 1H), 4.37 (t, J = 8.8
		Hz, 1H), 4.02 (s, 3H), 3.55-3.40 (m, 5H), 3.26-
		3.10 (m, 2H), 2.60 (d, J = 4.4 Hz, 3H), 2.04-
		1.56 (m, 7H), 1.20-0.95 (m, 5H), 0.91 (d, J =
		6.4 Hz, 3H), 0.82 (d, J = 6.8 Hz, 3H). MS
		(ESI, m/e) [M + 1]+ 600.3.
	56	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.16-
		10.12 (m, 1H), 8.48 (d, J = 8.0 Hz, 1H), 7.57-
		7.51 (m, 1H), 7.47-7.45 (m, 1H), 7.41-7.33 (m,
		1H), 7.16-7.09 (m, 2H), 7.07-7.05 (m, 1H),
		6.95-6.88 (m, 2H), 6.81-6.76 (m, 2H), 6.70 (s,
		1H), 4.42-4.36 (m, 1H), 4.02 (d, J = 4.0 Hz,
		3H), 3.70-3.68 (m, 2H), 3.64 (s, 1H), 3.47-3.38
		(m, 2H), 3.29-3.25 (m, 1H), 3.12-3.06 (m, 2H),
		2.99-2.95 (m, 1H), 2.66-2.59 (m, 2H), 2.54-
		2.52 (m, 3H), 2.45-2.34 (m, 1H), 1.89-1.81 (m,
		2H), 1.73-1.56 (m, 4H), 1.23-1.15 (m, 6H),
		1.04-0.99 (m, 1H). MS (ESI, m/e) [M + 1]+
		642.5.
	57	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.15-
		10.12 (m, 1H), 8.50 (d, J = 8.0 Hz, 1H), 7.55-
		7.45 (m, 2H), 7.39-7.24 (m, 3H), 7.11-7.07 (m,
		2H), 6.93-6.90 (m, 1H), 6.78-6.69 (m, 2H),
		4.40-4.35 (m, 1H), 4.02 (d, J = 4.0 Hz, 3H),
		3.74-3.64 (m, 1H), 3.45-3.41 (m, 1H), 3.13-
		3.00 (m, 3H), 2.89-2.79 (m, 2H), 2.56-2.54 (m,
		3H), 2.03-1.95 (m, 1H), 1.87-1.82 (m, 1H),
		1.73-1.57 (m, 4H), 1.23-1.11 (m, 8H). MS
		(ESI, m/e) [M + 1]+ 618.4.
	58	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.13
		(s, 1H), 9.04 (s, 1H), 8.88-8.73 (m, 1H), 8.71
		(d, J = 4.8 Hz, 1H), 8.25 (d, J = 8.0 Hz, 1H),
		7.57-7.29 (m, 4H), 7.12 (d, J = 8.4 Hz, 1H),
		6.76 (s, 1H), 4.47-4.40 (m, 1H), 3.59-3.45 (m,
		2H), 3.32-3.10 (m, 4H), 2.94-2.87 (m, 1H),
		2.58 (d, J = 4.4 Hz, 3H), 1.94-1.40 (m, 7H),
		1.21-0.95 (m, 5H), 0.74 (d, J = 6.4 Hz, 3H),
		0.70 (d, J = 6.8 Hz, 3H). MS (ESI, m/e)
		[M + 1]+ 561.4.
	59	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 8.48 (d, J = 8.4 Hz, 1H), 7.57-7.30 (m,
		4H), 7.12 (d, J = 8.4 Hz, 1H), 6.95 (d, J = 1.0
		Hz, 1H), 6.77 (s, 1H), 5.45-5.35 (m, 1H), 4.38-
		4.32 (m, 1H), 3.59-3.45 (m, 2H), 3.30-3.12 (m,
		4H), 2.93-2.87 (m, 1H), 2.58 (d, J = 4.4 Hz,
		3H), 1.90-1.40 (m, 7H), 1.35 (t, J = 7.2 Hz,
		6H), 1.20-0.95 (m, 5H), 0.75 (d, J = 6.8 Hz,
		3H), 0.70 (d, J = 6.4 Hz, 3H). MS (ESI, m/e)
		[M + 1]+ 592.5.
	60	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.32
		(s, 1H), 9.01 (d, J = 7.6 Hz, 1H), 7.57-7.30 (m,
		9H), 7.13 (s, 1H), 7.12 (d, J = 7.6 Hz, 1H),
		6.76 (s, 1H), 5.80 (d, J = 7.6 Hz, 1H), 4.04 (s,
		3H), 3.59-3.44 (m, 2H), 3.30-3.12 (m, 4H),
		2.93-2.87 (m, 1H), 2.57 (d, J = 4.4 Hz, 3H),
		1.48-1.38 (m, 1H), 0.76-0.66 (m, 6H). MS
		(ESI, m/e) [M + 1]+ 558.3.
	61	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 8.24 (s, 1H), 8.10-8.05 (m, 3H), 7.93
		(s, 1H), 7.57-7.30 (m, 3H), 7.11 (d, J = 8.0 Hz,
		1H), 6.76 (s, 1H), 4.43-4.35 (m, 1H), 3.85 (s,
		3H), 3.59-3.45 (m, 2H), 3.32-3.10 (m, 4H),
		2.94-2.87 (m, 1H), 2.58 (d, J = 4.4 Hz, 3H),
		1.85-1.40 (m, 7H), 1.21-0.95 (m, 5H), 0.74 (d,
		J = 6.4 Hz, 3H), 0.69 (d, J = 6.4 Hz, 3H). MS
		(ESI, m/e) [M + 1]+ 564.4.
	62	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.17-
		10.12 (m, 1H), 8.51-8.47 (m, 1H), 7.58-7.46
		(m, 2H), 7.41-7.34 (m, 1H), 7.20-6.99 (m, 5H),
		6.91-6.89 (m, 1H), 6.85-6.81 (m, 1H), 6.70 (s,
		1H), 4.43-4.36 (m, 1H), 4.02-4.01 (m, 3H),
		3.65-3.59 (m, 1H), 3.46-3.40 (m, 2H), 3.31-
		3.26 (m, 2H), 3.13-3.04 (m, 2H), 2.98-2.92 (m,
		1H), 2.68-2.60 (m, 1H), 2.55-2.53 (m, 3H),
		2.47-2.31 (m, 1H), 2.23-2.15 (m, 3H), 1.89-
		1.82 (m, 1H), 1.75-1.54 (m, 3H), 1.23-1.14 (m,
		6H). MS (ESI, m/e) [M + 1]+ 626.4.
	63	1H NMR (400 MHz, DMSO- d6) δ ppm: 10.10
		(s, 1H), 8.46 (d, J = 8.6 Hz, 1H), 7.58-7.47 (m,
		2H), 7.46 (d, J = 1.8 Hz, 1H) 7.41-7.28 (m,
		1H), 7.11 (d, J = 7.8 Hz, 1H), 7.07-7.03 (m,
		1H), 6.74 (s, 1H), 4.42-4.31 (m, 1H), 4.02 (s,
		3H), 3.65-3.54 (m, 1H), 3.52-3.37 (m, 3H),
		3.23-3.05 (m, 3H), 2.84-2.78 (m, 1H), 2.58 (d,
		J = 4.4 Hz, 3H), 2.39-2.22 (m, 2H), 2.03-1.50
		(m, 7H), 1.21-1.08 (m, 4H). MS (ESI, m/e)
		[M + 1]+ 560.4.
	64	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.15
		(s, 1H), 8.38 (d, J = 7.2 Hz, 1H), 8.24 (s, 1H),
		7.55-7.27 (m, 3H), 7.13 (d, J = 8.4 Hz, 1H),
		6.76 (s, 1H), 4.52-4.45 (m, 1H), 4.13 (s, 3H),
		3.58-3.45 (m, 2H), 3.32-3.12 (m, 4H), 2.94-
		2.87 (m, 1H), 2.58 (d, J = 4.4 Hz, 3H), 1.90-
		1.40 (m, 7H), 1.21-0.95 (m, 5H), 0.76 (d, J =
		6.4 Hz, 3H), 0.71 (d, J = 6.4 Hz, 3H). MS
		(ESI, m/e) [M + 1]+ 565.5.
	65	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.47-8.44 (m, 1H), 7.53-7.46 (m, 3H),
		7.21-7.06 (m, 3H), 6.68-6.65 (m, 2H), 4.40-
		4.35 (m, 1H), 4.02 (s, 3H), 3.54-3.38 (m, 3H),
		3.31-3.29 (m, 2H), 2.98-2.91 (m, 2H), 2.68-
		2.65 (m, 1H), 2.59-2.56 (m, 3H), 2.34-2.31 (m,
		1H), 2.02-1.95 (m, 6H), 1.85-1.81 (m, 1H),
		1.75-1.67 (m, 2H), 1.48-1.44 (m, 2H), 1.23-
		1.14 (m, 5H). MS (ESI, m/e) [M + 1]+ 576.5.
	66	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.15
		(s, 1H), 8.74 (d, J = 8.0 Hz, 1H), 7.54-7.25 (m,
		8H), 7.20-7.12 (m, 2H), 6.95 (s, 1H), 6.77 (s,
		1H), 4.83-4.77 (m, 1H), 3.94 (s, 3H), 3.59-3.34
		(m, 2H), 3.31 (s, 1H), 3.24-3.12 (m, 3H), 3.07-
		3.01 (m, 1H), 2.92-2.88 (m, 1H), 2.57 (d, J =
		4.0 Hz, 1H), 1.48-1.40 (m, 1H), 1.23-1.16 (m,
		1H), 0.76-0.69 (m, 6H). MS (ESI, m/e) [M + 1]+
		572.3.
	67	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.18
		(s, 1H), 8.62 (d, J = 12.0 Hz, 1H), 7.56-7.46
		(m, 3H), 7.41-7.30 (m, 1H), 7.12 (d, J = 8.0
		Hz, 1H), 7.06 (d, J = 4.0 Hz, 1H), 6.76 (s, 1H),
		4.49-4.45 (m, 1H), 4.03 (s, 3H), 3.57-3.45 (m,
		2H), 3.30 (s, 1H), 3.23-3.15 (m, 2H), 3.12-3.05
		(m, 2H), 2.93-2.88 (m, 1H), 2.57 (d, J = 8.0
		Hz, 1H), 2.07-1.99 (m, 3H), 1.92-1.65 (m,
		4H), 1.46-1.42 (m, 2H), 1.35-1.23 (m, 1H),
		0.75-0.68 (m, 6H). MS (ESI, m/e) [M + 1]+
		600.4.
	68	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.48 (d, J = 8.0 Hz, 1H), 8.23-8.17 (m,
		1H), 7.57-7.32 (m, 3H), 7.13 (d, J = 8.0 Hz,
		1H), 7.06 (s, 1H), 6.90 (s, 1H), 4.42-4.35 (m,
		1H), 4.02 (s, 3H), 3.95-3.74 (m, 2H), 3.64-3.38
		(m, 3H), 3.32-3.07 (m, 3H), 2.87-2.80 (m, 1H),
		1.90-1.40 (m, 7H), 1.21-0.95 (m, 5H), 0.76 (d,
		J = 6.4 Hz, 3H), 0.71 (d, J = 6.4 Hz, 3H). MS
		(ESI, m/e) [M + 1]+ 632.5.
	69	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.63 (d, J = 8.2 Hz, 1H), 8.00-7.94 (m,
		1H), 7.86 (d, J = 7.8 Hz, 1H), 7.64-7.46 (m,
		4H), 7.42-7.28 (m, 1H), 7.11 (d, J = 8.2 Hz,
		1H), 6.74 (s, 1H), 4.47-4.35 (m, 1H), 3.60-3.43
		(m, 2H), 3.31-3.05 (m, 4H), 2.95-2.85 (m, 1H),
		2.57 (d, J = 4.4 Hz, 3H), 1.94-1.53 (m, 6H),
		1.50-1.38 (m, 1H), 1.20-1.01 (m, 5H), 0.78-
		0.62 (m, 6H). MS (ESI, m/e) [M + 1]+ 594.4.
	70	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.03
		(s, 1H), 8.43 (d, J = 8.4 Hz. 1H), 7.49-7.42 (m,
		4H), 7.08-7.02 (m, 2H), 6.36 (s, 1H), 4.39-4.36
		(m, 1H), 4.02 (s, 3H), 3.46-3.41 (m, 2H), 3.07-
		3.01 (m, 4H), 2.98-2.96 (m, 2H), 2.54-2.51 (m,
		3H).1.81-1.67 (m, 7H), 1.05-1.02 (m, 6H),
		0.79-0.72 (m, 3H). MS (ESI, m/e) [M + 1]+
		564.5.
	71	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 8.33 (d, J = 8.4 Hz, 1H), 7.73-7.62 (m,
		2H), 7.53-7.32 (m, 5H), 7.10-7.05 (m, 1H),
		6.75 (s, 1H), 4.45-4.41 (m, 1H), 3.46-3.41 (m,
		2H), 3.22-3.16 (m, 2H), 2.98-2.96 (m, 1H),
		2.64-2.60 (m, 3H), 2.31 (s, 3H), 1.81-1.67 (m,
		7H), 1.21-1.02 (m, 5H), 0.65-0.55 (m, 6H).
		MS (ESI, m/e) [M + 1]+ 574.5.
	72	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.49 (d, J = 8.2 Hz, 1H), 7.60-7.44 (m,
		3H), 7.44-7.26 (m, 1H), 7.11 (d, J = 8.2 Hz,
		1H), 7.07-7.03 (m, 1H), 6.76 (s, 1H), 4.43-4.31
		(m, 1H), 4.02 (s, 3H), 3.53-3.44 (m, 2H), 3.23-
		3.15 (m, 5H), 3.12-3.04 (m, 2H), 2.94-2.88 (m,
		1H), 2.57 (d, J = 4.6 Hz, 3H), 2.08-1.75 (m,
		4H), 1.65-1.52 (m, 1H), 1.50-1.28 (m, 4H),
		1.20-1.14 (m, 2H), 0.78-0.66 (m, 6H). MS
		(ESI, m/e) [M + 1]+ 594.5.
	73	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.48 (d, J = 8.0 Hz, 1H), 7.64-7.30 (m,
		4H), 7.12 (d, J = 7.6 Hz, 1H), 7.06 (s, 1H),
		6.78 (s, 1H), 4.42-4.35 (m, 1H), 4.02 (s, 3H),
		3.83-3.74 (m, 1H), 3.53-3.38 (m, 3H), 3.22-
		3.12 (m, 2H), 3.09-2.99 (m, 1H), 2.59 (d, J =
		4.4 Hz, 3H), 2.56-2.40 (m, 2H), 1.90-1.54 (m,
		6H), 1.21-0.95 (m, 5H). MS (ESI, m/e) [M + 1]+
		604.4.
	74	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.18-
		10.08 (m, 1H), 8.55-8.40 (m, 1H), 7.57-7.48
		(m, 1H), 7.47-7.43 (m, 1H), 7.43-7.32 (m, 1H),
		7.32-7.15 (m, 3H), 7.15-6.95 (m, 4H), 6.72 (s,
		1H), 4.48-4.30 (m, 1H), 4.06-3.90 (m, 3H),
		3.72-3.58 (s, 1H), 3.50-3.38 (m, 1H), 3.16-2.82
		(m, 4H), 2.70-2.60 (m, 1H), 2.59-2.52 (m, 3H),
		2.48-2.38 (m, 1H), 1.95-1.44 (m, 7H), 1.20-
		0.98 (m, 5H). MS (ESI, m/e) [M + 1]+ 646.5.
	75	1H NMR (400 MHz DMSO-d6) δ ppm: 10.08
		(s, 1H), 8.45 (d, J = 7.8 Hz, 1H), 7.62-7.25 (m,
		4H), 7.20-6.94 (m, 2H), 6.34 (s, 1H), 4.38 (t, J =
		8.2 Hz, 1H), 4.02 (s, 3H), 3.60-3.32 (m, 3H),
		3.21-3.02 (m, 3H), 2.84-2.68 (m, 2H), 2.54 (d,
		J = 3.6 Hz, 3H), 1.83-1.59 (m, 7H), 1.15-0.99
		(m, 7H), 0.71 (d, J = 6.2 Hz, 3H). MS (ESI)
		m/e [M + 1]+ 564.4.
	76	1H NMR (400 MHz, Methanol-d4) δ ppm:
		7.48-7.29 (m, 3H), 7.18-7.11 (m, 1H), 7.02-
		6.84 (m, 5H), 4.44 (d, J = 8.8 Hz, 1H), 4.11-
		4.05 (m, 3H), 3.85-3.75 (m, 1H), 3.67-3.37 (m,
		4H), 3.20-3.07 (m, 3H), 2.85-2.71 (m,3H),
		1.98-1.65 (m, 6H), 1.36-1.07 (m, 6H). MS
		(ESI, m/e) [M + 1]+ 630.5.
	77	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.15
		(s, 1H), 8.24 (d, J = 8.4 Hz, 1H), 7.53-7.32 (m,
		4H), 7.15-7.05 (m, 3H), 6.75 (s, 1H), 4.30-4.25
		(m, 1H), 3.46-3.41 (m, 2H), 3.22-3.16 (m, 2H),
		2.98-2.96 (m, 1H), 2.64-2.60 ( m, 3H), 1.99-
		1.97 (m, 1H), 1.81-1.67 (m, 7H), 1.53-1.47 (m,
		2H), 1.21-1.02 (m, 5H), 0.65-0.55 (m, 6H).
		MS (ESI, m/e) [M + 1]+ 573.5.
	78	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 8.34 (d, J = 8.2 Hz, 1H), 7.81 (d, J =
		8.0 Hz, 2H), 7.58-7.46 (m, 2H), 7.42-7.29 (m,
		1H), 7.27 (d, J = 8.2 Hz, 2H), 7.10 (d, J = 8.2
		Hz, 1H), 6.75 (s, 1H), 4.44-4.34 (m, 1H), 3.53-
		3.44 (m, 2H), 3.30-3.25 (m 1H), 3.23-3.12 (m,
		2H), 2.95-2.87 (m, 1H), 2.57 (d, J = 4.4 Hz,
		3H), 2.36 (s, 3H), 1.94-1.51 (m, 7H), 1.48-1.41
		(m, 1H), 1.19-1.01 (m, 5H), 0.75-0.68 (m, 6H).
		MS (ESI, m/e) [M + 1]+ 574.5.
	79	1H NMR (400 MHz DMSO-d6) δ ppm: 10.04
		(s, 1H), 8.83 (d, J = 8.4 Hz, 1H), 8.51 (s, 1H),
		7.92 (s, 2H), 7.67-7.31 (m, 7H), 7.11 (d, J =
		8.0 Hz, 1H), 6.95 (s, 1H), 6.76 (s, 1H), 4.98 (s,
		1H), 3.91 (s, 3H), 3.57-3.16 (m, 6H), 3.11-3.06
		(m, 2H), 2.88 (s, 1H), 2.57 (d, J = 2.8 Hz, 3H),
		1.48 (s, 6H), 1.46-1.39 (m, 1H), 0.77-0.64 (m,
		6H). MS (ESI) m/e [M + 1]+ 742.4.
	80	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.13
		(s, 1H), 8.46 (d, J = 7.8 Hz, 1H), 7.59 (d, J =
		7.0 Hz, 2H), 7.53 (d, J = 7.8 Hz, 1H), 7.45 (s,
		1H), 7.38-7.31 (m, 2H), 7.25 (d, J = 7.4 Hz,
		2H), 7.14-7.02 (m, 2H), 6.75 (d, J = 5.2 Hz,
		1H), 4.39 (d, J = 7.6 Hz, 1H), 4.02 (d, J = 3.2
		Hz, 3H), 3.73 (s, 1H), 3.46-3.32 (m, 3H), 3.12-
		3.06 (m, 2H), 2.97 (s, 1H), 2.78 (s, 1H), 2.62
		(s, 1H), 2.55 (d, J = 3.2 Hz, 3H), 1.84 (s, 2H),
		1.69 (s, 2H), 1.60 (s, 2H), 1.15 (d, J = 6.2 Hz,
		3H), 1.00 (d, J = 11.2 Hz, 1H). MS (ESI) m/e
		[M + 1]+ 680.4
	81	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.12
		(s, 1H), 8.48 (d, J = 8.0 Hz, 1H), 7.61-7.50 (m,
		2H), 7.46 (d, J = 4.0 Hz, 1H), 7.41-7.31 (m,
		1H), 7.13-7.11 (m, 1H), 7.06 (d, J = 4.0 Hz,
		1H), 6.79 (s, 1H), 4.40-4.35 (m, 1H), 4.02 (s,
		3H), 3.77-3.72 (m, 1H), 3.77-3.72 (m, 1H),
		3.64-3.50 (m, 2H), 3.30-3.24 (m, 2H), 3.19-
		3.12 (m, 1H), 3.05-3.01 (m, 1H), 2.57 (d, J =
		4.0 Hz, 3H), 1.87-1.81 (m, 2H), 1.74-1.70 (m,
		2H), 1.62-1.55 (m, 2H), 1.23-1.15 (m, 6H),
		0.96-0.92 (m, 3H). MS (ESI, m/e) [M + 1]+
		618.5.
	82	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 8.48 (d, J = 8.4 Hz, 1H), 7.58-7.30 (m,
		4H), 7.12 (d, J = 8.4 Hz, 1H), 7.06 (s, 1H),
		6.75 (s, 1H), 4.48-4.43 (m, 1H), 4.01 (s, 3H),
		3.57-3.45 (m, 2H), 3.25-3.12 (m, 4H), 2.95-
		2.89 (m, 1H), 2.13-2.06 (m, 1H), 1.77-1.28 (m,
		14H), 0.75 (d, J = 6.4 Hz, 3H), 0.70 (d, J = 6.4
		Hz, 3H). MS (ESI, m/e) [M + 1]+ 581.5.
	83	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 8.48 (d, J = 8.4 Hz, 1H), 7.57-7.31 (m,
		3H), 7.12 (d, J = 8.4 Hz, 1H), 7.06 (s, 1H),
		7.05-6.93 (m, 2H), 6.77 (s, 1H), 4.48-4.43 (m,
		1H), 4.01 (s, 3H), 3.57-3.35 (m, 4H), 3.25-3.12
		(m, 2H), 2.98-2.89 (m, 1H), 2.13-2.06 (m, 1H),
		1.77-1.28 (m, 14H), 0.76 (d, J = 6.4 Hz, 3H) ,
		0.71 (d, J = 6.4 Hz, 3H). MS (ESI, m/e)
		[M + 1]+ 564.5.
	84	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.08
		(s, 1H), 8.45 (d, J = 7.2 Hz, 1H), 7.57-7.28 (m,
		3H), 7.12 (d, J = 8.4 Hz, 1H), 7.07 (s, 1H),
		6.75 (s, 1H), 4.73-4.65 (m, 1H), 4.43-4.38 (m,
		1H), 3.58-3.44 (m, 2H), 3.32-3.07 (m, 4H),
		2.94-2.87 (m, 1H), 2.58 (d, J = 4.4 Hz, 3H),
		1.95-1.40 (m, 7H), 1.30-1.26 (m, 6H), 1.20-
		1.11 (m, 4H), 1.08-0.95 (m, 1H), 0.74 (d, J =
		6.8 Hz, 3H), 0.70 (d, J = 6.8 Hz, 3H). MS
		(ESI, m/e) [M + 1]+ 618.5.
	85	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.15
		(s, 1H), 8.54 (d, J = 8.4 Hz, 1H), 7.58-7.43 (m,
		3H), 7.43-7.29 (m, 1H), 7.11 (d, J = 8.2 Hz,
		1H), 7.06 (d, J = 2.0 Hz, 1H), 6.75 (s, 1H),
		4.47-4.35 (m, 1H), 4.03 (s, 3H), 3.93-3.82 (m,
		2H), 3.60-3.42 (m, 2H), 3.26-3.04 (m, 7H),
		2.95-2.85 (m, 1H), 2.57 (d, J = 4.6 Hz, 3H),
		2.15-2.00 (m, 1H), 1.75-1.65 (m, 1H), 1.52-
		1.40 (m, 3H), 0.76-0.66 (m, 6H). MS (ESI,
		m/e) [M + 1]+ 566.5
	86	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.44 (d, J = 8.4 Hz, 1H), 7.45-7.42 (m,
		3H), 7.13-7.10 (m, 4H), 4.39-4.36 (m, 1H),
		4.02 (s, 3H), 3.56-3.51 (s, 4H), 3.26-3.21 (m,
		4H), 2.89-2.85 (m, 1H), 1.91-1.67 (m, 14H),
		1.20-1.04 (m, 4H), 0.84-0.75 (m, 7H). MS
		(ESI, m/e) [M + 1]+ 648.5.
	87	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.53 (d, J = 8.4 Hz. 1H), 7.49-7.42 (m,
		4H), 7.08-7.02 (m, 2H), 6.76 (s, 1H), 4.39-4.36
		(m, 1H), 4.02 (s, 3H), 3.46-3.41 (m, 2H), 3.07-
		3.01 (m, 3H), 2.54-2.51 (m, 3H), 1.81-1.67 (m,
		2H), 1.51-1.17 (m, 7H), 1.05-1.02 (m, 2H),
		0.79-0.72 (m, 6H), 0.63-0.55 (m, 6H). MS
		(ESI, m/e) [M + 1]+ 592.5.
	88	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 8.43 (d, J = 8.4 Hz. 1H), 7.49-7.42 (m,
		4H), 7.08-7.02 (m, 2H), 6.65 (s, 1H), 4.40-4.36
		(m, 1H), 4.02 (s, 3H), 3.46-3.41 (m, 4H), 3.07-
		3.01 (m, 2H), 2.78-2.76 (m, 1H), 2.54-2.51 (m,
		3H).1.81-1.67 (m, 11H), 1.05-1.02 (m, 8H),
		0.79-0.72 (m, 2H). MS (ESI, m/e) [M + 1]+
		618.6.
	89	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 8.49 (d, J = 8.0 Hz, 1H), 7.58-7.30 (m,
		4H), 7.12 (d, J = 8.0 Hz, 1H), 7.07 (s, 1H),
		6.75 (s, 1H), 4.40-4.34 (m, 1H), 4.02 (s, 3H),
		3.59-3.46 (m, 2H), 3.27-3.12 (m, 4H), 2.95-
		2.87 (m, 1H), 2.58 (d, J = 4.4 Hz, 3H), 1.90-
		1.54 (m, 5H), 1.50-1.25 (m, 3H), 1.21-0.85 (m,
		6H), 0.75 (d, J = 6.8 Hz, 3H), 0.70 (d, J = 6.4
		Hz, 3H). MS (ESI, m/e) [M + 1]+ 578.5.
	90	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 8.42 (d, J = 8.8 Hz, 1H), 7.52-7.46 (m,
		4H), 7.17 (d, J = 8.4 Hz, 1H), 7.05 (s, 1H),
		6.74 (s, 1H), 4.82-4.78 (m, 1H), 4.05 (s, 3H),
		3.50-3.47 (m, 2H), 3.28-3.21 (m, 3H), 3.03-
		2.98 (m, 1H), 2.58-2.52 (m, 3H), 1.49-1.34 (m,
		1H), 0.93-0.68 (m, 9H), 0.45-0.07 (m, 8H).
		MS (ESI, m/e) [M + 1]+ 576.5.
	91	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.05
		(s, 1H), 8.42 (d, J = 8.8 Hz, 1H), 7.52-7.46 (m,
		4H), 7.17 (d, J = 8.4 Hz, 1H), 6.93 (d, J = 1.8
		Hz, 1H), 6.74 (s, 1H), 5.48-5.34 (m, 1H), 4.82-
		4.78 (m, 1H), 3.50-3.47 (m, 2H), 3.28-3.21 (m,
		3H), 3.17-3.15 (m, 1H), 3.03-2.98 (m, 1H),
		2.58-2.52 (m, 3H), 1.49-1.34 (m, 7H), 0.93-
		0.68 (m, 10H), 0.45-0.07 (m, 8H). MS (ESI,
		m/e) [M + 1]+ 604.5.
	92	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(d, J = 8.8 Hz, 1H), 8.47 (d, J = 8.0 Hz, 1H),
		7.59-7.30 (m, 4H), 7.18-7.00 (m, 6H), 6.82 (d,
		J = 4.4 Hz, 1H), 4.44-4.37 (m, 1H), 4.02 (s,
		3H), 3.74-3.46 (m, 3H), 3.27-3.00 (m, 5H),
		2.86-2.65 (m, 2H), 2.58-2.54 (m, 3H), 2.04-
		1.54 (m, 6H), 1.20-0.95 (m, 5H). MS (ESI,
		m/e) [M + 1]+ 638.5.
	93	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 8.40 (d, J = 8.8 Hz, 1H), 7.57-7.50 (m,
		1H), 7.50-7.43 (m, 2H), 7.40-7.32 (m, 1H),
		7.11 (d, J = 7.8 Hz, 1H), 7.08-7.02 (m, 1H),
		6.74 (s, 1H), 4.85-4.74 (m, 1H), 4.04 (s, 3H),
		3.61-3.45 (m, 2H), 3.29-3.27 (m, 1H), 3.25-
		3.12 (m, 2H), 2.92-2.82 (m, 1H), 2.60-2.55 (m,
		3H), 2.04-1.91 (m, 1H), 1.53-1.35 (m, 1H),
		0.85-0.65 (m, 9H), 0.48-0.05 (m, 8H). MS
		(ESI, m/e) [M + 1]+ 576.5.
	94	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 8.44 (d, J = 8.4 Hz, 1H), 7.53 (d, J =
		19.0 Hz, 1H), 7.45 (d, J = 2.0 Hz, 1H), 7.39-
		7.28 (m, 2H), 7.10 (d, J = 8.2 Hz, 1H), 7.08-
		7.03 (m, 1H), 6.34 (s, 1H), 4.44-4.30 (m, 1H),
		4.02 (s, 3H), 3.66-3.52 (m, 1H), 3.47-3.38 (m,
		1H), 3.21-2.81 (m, 6H), 2.54 (d, J = 4.6 Hz,
		3H), 1.93-1.52 (m, 6H), 1.21-0.94 (m, 6H),
		0.54-0.41 (m, 1H), 0.39-0.29 (m, 1H), 0.29-
		0.18 (m, 1H), 0.11-0.04 (m, 1H), 0.00--0.1 (m,
		1H). MS (ESI, m/e) [M + 1]+ 576.5.
	95	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.06
		(s, 1H), 8.43 (d, J = 8.4 Hz, 1H), 7.48-7.43 (m,
		2H), 7.40-7.34 (m, 1H), 7.34-7.28 (m, 1H),
		7.09 (d, J = 8.4 Hz, 1H), 7.05 (d, J = 2.0 Hz,
		1H), 6.32 (s, 1H), 4.42-4.34 (m, 1H), 4.02 (s,
		3H), 3.58-3.40 (m, 2H), 3.22-3.02 (m, 4H),
		2.54 (d, J = 4.6 Hz, 3H), 2.02-1.50 (m, 8H),
		1.43-1.32 (m, 1H), 1.23-1.07 (m, 4H), 1.07-
		0.95 (m, 4H). MS (ESI, m/e) [M + 1]+ 550.5.
	96	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.13-
		10.10 (m, 1H), 8.47 (d, J = 8.0 Hz, 1H), 7.56-
		7.49 (m, 2H), 7.46-7.45 (m, 1H), 7.43-7.33 (m,
		1H), 7.26-7.21 (m, 1H), 7.16-7.10 (m, 4H),
		7.07-7.06 (m, 1H), 6.79 (s, 1H), 4.41-4.36 (m,
		1H), 4.02 (d, J = 4.0 Hz, 3H), 3.54-3.40 (m,
		4H), 3.26-3.13 (m, 2H), 2.93-2.88 (m, 1H),
		2.58 (d, J = 4.0 Hz, 3H), 2.47-2.45 (m, 1H),
		1.87-1.81 (m, 2H), 1.73-1.69 (m, 2H), 1.63-
		1.56 (m, 2H), 1.23-1.15 (m, 5H). MS (ESI,
		m/e) [M + 1]+ 626.5.
	97	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.28
		(s, 0.19H), 10.02 (s, 0.78H), 9.03 (d, J = 8.0 Hz,
		0.2H), 8.65 (d, J = 8.0 Hz, 0.8H), 7.63-7.28 (m,
		5H), 7.22-7.05 (m, 4H), 7.01-6.99 (m, 0.8H),
		6.81 (s, 1H), 4.96-4.92 (m, 0.8H), 4.66-4.61 (m,
		0.2H), 4.05-4.02 (m, 3H), 3.85-3.80 (m, 1H),
		3.65-3.52 (m, 2H), 3.31-3.19 (m, 2H), 3.08-2.82
		(m, 3H), 2.66-2.62 (m, 3H), 2.20-2.03 (m, 2H),
		1.53-1.48 (m, 2H), 0.81-0.75 (m, 6H). MS (ESI,
		m/e) [M + 1]+ 598.5.
	98	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.03
		(s, 1H), 8.43 (d, J = 8.4 Hz. 1H), 7.49-7.42 (m,
		4H), 7.08-7.02 (m, 2H), 6.36 (s, 1H), 4.39-4.36
		(m, 1H), 4.02 (s, 3H), 3.46-3.41 (m, 2H), 3.07-
		3.01 (m, 4H), 2.98-2.96 (m, 2H), 2.54-2.51 (m,
		3H).1.81-1.67 (m, 7H), 1.05-1.02 (m, 6H),
		0.79-0.72 (m, 3H). MS (ESI, m/e) [M + 1]+
		550.5.
	99	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(d, J = 4.0 Hz, 1H), 8.47 (d, J = 7.4 Hz, 1H),
		7.51 (s, 1H), 7.46 (s, 1H), 7.38-7.33 (m, 2H),
		7.22-7.18 (m, 2H), 7.15-7.03 (m, 3H), 7.00-
		6.95 (m, 2H), 6.35 (s, 1H), 4.40 (t, J = 8.4 Hz,
		1H), 4.03 (s, 3H), 3.62 (t, J = 15.6 Hz, 1H),
		3.37-3.32 (m, 1H), 3.17-3.01 (m, 5H), 2.97 (s,
		1H), 2.83-2.75 (m, 2H), 2.54 (d, J = 4.0 Hz,
		3H), 2.43-2.41 (m, 2H), 2.05 (s, 1H), 1.85 (s,
		2H), 1.70 (s, 2H), 1.61 (s, 2H), 1.23-1.16 (m,
		3H), 1.05-0.99 (m, 1H). MS (ESI) m/e [M + 1]+
		626.4
	100	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.45-8.43(m, 1H), 7.56-7.27 (m, 4H),
		7.11-7.06 (m, 2H), 6.89-6.66 (m, 4H), 6.41 (d,
		J = 7.4 Hz, 1H), 4.39 (t, J = 74 Hz, 1H), 4.02
		(d, J = 5.8 Hz, 3H), 3.75-3.62 (m, 4H), 3.50-
		3.38 (m, 2H), 3.20-2.91 (m, 5H), 2.80 (d, J =
		11.2 Hz, 1H), 2.68 (d, J = 9.8 Hz, 1H), 2.55 (d,
		J = 4.4 Hz, 3H), 2.40 (d, J = 13.4 Hz, 1H),
		2.24 (d, J = 13.4 Hz, 1H), 1.84 (s, 2H), 1.70 (s,
		2H), 1.59 (s, 2H), 1.16 (s, 2H), 1.02 (s, 1H),
		0.64-0.55 (m, 3H). MS (ESI) m/e [M + 1]+
		670.4.
	101	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.06
		(s, 1H), 8.44 (d, J = 8.0 Hz, 1H), 7.55-7.47 (m,
		2H), 7.45 (d, J = 4.0 Hz, 1H), 7.40-7.29 (m,
		1H), 7.11 (d, J = 8.0 Hz, 1H), 7.05 (d, J = 4.0
		Hz, 1H), 6.74 (s, 1H), 4.38-4.34 (m, 1H), 4.03-
		4.02 (m, 3H), 3.57-3.45 (m, 2H), 3.23-3.12 (m,
		3H), 2.92-2.89 (m, 1H), 2.58 (d, J = 4.0 Hz,
		3H), 1.88-1.75 (m, 4H), 1.61-1.58 (m, 1H),
		1.47-1.42 (m, 2H), 1.24-1.15 (m, 5H), 1.07-1.00
		(m, 2H), 0.85-0.82 (m, 3H), 0.85-0.82 (m, 3H),
		0.75-0.68 (m, 6H). MS (ESI, m/e) [M + 1]+
		592.6.
	102	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.06 (s,
		1H), 8.44 (d, J = 8.2 Hz, 1H), 7.53 (s, 1H), 7.45
		(d, J = 2.0 Hz, 1H), 7.33-7.29 (m, 2H), 7.11-
		7.02 (m, 2H), 6.42 (s, 1H), 4.38 (t, J = 8.4 Hz,
		1H), 4.03 (s, 3H), 3.55-3.45 (m, 2H), 3.21-2.98
		(m, 5H), 2.85 (s, 2H), 2.56 (d, J = 4.4 Hz, 3H),
		1.88-1.52 (m, 6H), 1.35-1.01 (m, 5H), 0.39 (s,
		2H), 0.24-0.11 (m, 2H). MS (ESI, m/e) [M + 1]+
		562.5
	103	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.14 (s,
		1H), 8.39-8.31 (m, 1H), 7.80 (d, J = 2.2 Hz,
		1H), 7.64 (d, J = 8.8 Hz, 1H), 7.58-7.51 (m,
		1H), 7.39-7.31 (m, 1H), 7.11 (d, J = 8.6 Hz, 1H),
		6.74 (s, 1H), 6.65 (d, J = 2.2 Hz, 1H), 4.7-
		4.92(m, 1H), 4.56-4.52 (m, 1H), 4.25-4.21 (m,
		2H), 3.85-3.75 (m, 2H), 3.71-3.51 (m, 4H), 3.9-
		3.05 (m, 4H), 2.65-2.55 (m, 3H), 1.81-1.61 (m,
		6H), 1.35-1.1 (s, 5H), 0.85-0.69 (m, 6H). MS
		(ESI, m/e) [M + 1]+ 594.8.
	104	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 8.44 (d, J = 8.0 Hz, 1H), 7.56-7.49 (m,
		2H), 7.46-7.44 (m, 1H), 7.40-7.30 (m, 1H), 7.11
		(d, J = 8.0 Hz, 1H), 7.07-7.05 (m, 1H), 6.75 (s,
		1H), 4.39-4.34 (m, 1H), 4.04-4.01 (m, 3H),
		3.57-3.45 (m, 2H), 3.23-3.12 (m, 2H), 2.94-2.88
		(m, 1H), 2.58 (d, J = 4.0 Hz, 3H), 1.90-1.78 (m,
		2H), 1.74-1.69 (m, 1H), 1.65-1.54 (m, 2H),
		1.49-1.40 (m, 1H), 1.35-1.20 (m, 4H), 1.10-0.99
		(m, 1H), 0.87-0.82 (m, 5H), 0.74-0.68 (m, 6H).
		MS (ESI, m/e) [M + 1]+ 578.5.
	105	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.08
		(s, 1H), 8.46 (d, J = 8.0 Hz, 1H), 7.57-7.28 (m,
		4H), 7.12 (d, J = 8.0 Hz, 1H), 7.06 (s, 1H),
		6.33 (s, 1H), 4.44-4.37 (m, 1H), 4.03 (s, 3H),
		3.59-3.46 (m, 2H), 3.17-3.06 (m, 2H), 2.98-
		2.92 (m, 2H), 2.78-2.70 (m, 2H), 2.58 (d, J =
		4.4 Hz, 3H), 1.90-1.54 (m, 6H), 1.20-0.95 (m,
		7H), 0.65-0.55 (m, 6H). MS (ESI, m/e) [M + 1]+
		578.5.
	106	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.13
		(s, 1H), 8.43 (d, J = 8.4 Hz, 1H), 7.49-7.42 (m,
		3H), 7.42-7.35 (m, 2H), 7.06 (s, 1H), 6.36 (s,
		1H), 4.39-4.36 (m, 1H), 4.02 (s, 3H), 3.46-3.41
		(m, 4H), 3.22-3.16 (m, 2H), 2.98-2.96 (m, 1H),
		2.54-2.52(m, 3H), 2.24-2.22 (m, 2H), 1.81-
		1.67 (m, 2H), 1.21-1.02 (m, 5H), 1.16-1.14 (m,
		5H). MS (ESI, m/e) [M + 1]+ 574.5.
	107	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.44 (d, J = 8.4 Hz, 1H), 7.45-7.42 (m,
		3H), 7.13-7.10 (m, 4H), 4.39-4.36 (m, 1H),
		4.02 (s, 3H), 3.56-3.51 (s, 3H), 3.46-3.41 (m,
		3H), 1.91-1.67 (m, 17H), 1.20-1.04 (m, 6H),
		0.84-0.75 (m, 7H). MS (ESI, m/e) [M + 1]+
		662.6
	108	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.45 (d, J = 7.6 Hz, 1H), 7.55 (s, 1H),
		7.45 (s, 1H), 7.38 (d, J = 3.8 Hz, 1H), 7.33 (d,
		J = 8.0 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H), 7.06
		(s, 1H), 6.31 (s, 1H), 4.39 (t, J = 8.4 Hz, 1H),
		4.02 (s, 3H), 3.57-3.47 (m, 2H), 3.20-2.91 (m,
		6H), 2.55 (d, J = 4.2 Hz, 3H), 1.82 (d, J = 10.8
		Hz, 2H), 1.77-1.52 (m, 8H), 1.45-1.39 (m,
		2H), 1.19-1.16 (m, 5H). MS (ESI) m/e [M + 1]+
		576.4.
	109	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.17-
		10.02 (m, 1H), 8.46 (d, J = 8.2 Hz, 1H), 7.55-
		7.29 (m, 4H), 7.23-7.05 (m, 5H), 6.92 (t, J =
		5.8 Hz, 2H), 6.42 (s, 1H), 4.40 (t, J = 7.6 Hz,
		1H), 4.03 (d, J = 4.4 Hz, 3H), 3.62-3.56 (m,
		2H), 3.17-2.99 (m, 4H), 2.82 (d, J = 10.0 Hz,
		1H), 2.70 (d, J = 10.0 Hz, 1H), 2.56 (d, J = 4.2
		Hz, 3H), 2.45 (d, J = 12.8 Hz, 1H), 2.29 (d, J =
		12.8 Hz, 1H), 2.01-1.97 (m, 1H), 1.84 (s, 2H),
		1.70 (s, 2H), 1.61 (s, 2H), 1.16 (s, 3H), 1.01 (d,
		J = 11.0 Hz, 1H), 0.59 (s, 3H). MS (ESI) m/e
		[M + 1]+ 640.4.
	110	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 9.03 (d, J = 8.2 Hz, 1H), 7.59-6.93 (m,
		4H), 6.31 (s, 1H), 4.47 (t, J = 8.2 Hz, 1H),
		3.56-3.49 (m, 2H), 3.19 (s, 2H), 3.15-3.09 m,
		2H), 2.94 (s, 2H), 2.55 (d, J = 4.4 Hz, 3H),
		2.47 (s, 3H), 1.86-1.50 (m, 10H), 1.43 (s, 2H),
		1.21-1.12 (m, 3H), 1.03 (d, J = 10.4 Hz, 1H),
		0.89-0.80 (m, 1H). MS (ESI) m/e [M + 1]+
		578.4.
	111	[0345] 1H NMR (400 MHz, DMSO-d6) δ
		ppm: 10.24 (s, 1H), 8.54 (d, J = 8.4 Hz, 1H),
		7.49-7.42 (m, 4H), 7.42-7.35 (m, 1H), 7.13-
		7.10 (m, 2H), 6.76 (m, 1H), 4.92-4.86 (m, 1H),
		4.02 (s, 3H), 3.46-3.41 (m, 2H), 3.22-3.16 (m,
		4H), 2.58-2.56 (m, 3H), 2.40-2.36 (m, 2H),
		1.81-1.67 (m, 11H), 1.55-1.52 (m, 3H), 0.74-
		0.65 (m, 6H). MS (ESI, m/e) [M + 1]+ 616.3.
	112	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.03
		(s, 1H), 8.53 (d, J = 8.4 Hz. 1H), 7.49-7.42 (m,
		4H), 7.08-7.02 (m, 2H), 6.36 (s, 1H), 4.39-4.36
		(m, 1H), 4.02 (s, 3H), 3.46-3.41 (m, 2H), 3.07-
		3.01 (m, 3H), 2.98-2.96 (m, 3H), 2.64-2.60(m,
		3H).1.81-1.67 (m, 6H), 1.05-1.02 (m, 3H),
		0.91-0.72 (m, 8H), 0.26-0.14 (m, 3H). MS
		(ESI, m/e) [M + 1]+ 590.3.
	113	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.03
		(s, 1H), 8.43 (d, J = 8.4 Hz. 1H), 7.49-7.42 (m,
		4H), 7.08-7.02 (m, 2H), 6.36 (s, 1H), 4.39-4.36
		(m, 1H), 4.02 (s, 3H), 3.46-3.41 (m, 2H), 3.07-
		3.01 (m, 3H), 2.98-2.96 (m, 3H), 2.64-2.60 (m,
		3H). 1.81-1.67 (m, 6H), 1.05-1.02 (m, 4H),
		0.51-0.42 (m, 4H), 0.26-0.14 (m, 3H). MS
		(ESI, m/e) [M + 1]+ 590.4.
	114	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.16
		(d, J = 4.0 Hz, 1H), 8.50 (d, J = 8.0 Hz, 1H),
		7.56-7.49 (m, 2H), 7.44-7.38 (m, 2H), 7.16-7.12
		(m, 2H), 6.48 (s, 1H), 4.88-4.83 (m, 1H), 4.11
		(s, 3H), 3.57 (d, J = 16.0 Hz, 2H), 3.51-3.46 (m,
		1H), 3.16-3.07 (m, 3H), 3.03-2.87 (m, 3H), 2.63
		(d, J = 4.0 Hz, 3H), 0.91-0.77 (m, 3H), 0.51-
		0.31 (m, 6H), 0.25-0.06 (m, 6H). MS (ESI, m/e)
		[M + 1]+ 574.5
	115	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.05
		(d, J = 8.0 Hz, 1H), 8.41-8.38 (m, 1H), 7.50 (d,
		J = 4.0 Hz, 1.5H), 7.43 (s, 0.5H), 7.38-7.31 (m,
		2H), 7.08 (d, J = 4.0 Hz, 1H), 6.93-6.91(m, 1H),
		6.40 (d, J = 4.0 Hz, 1H), 5.43-5.39 (m, 1H),
		4.80-4.75(m, 1H), 4.54-4.38 (m, 1H), 3.10-3.01
		(m, 4H), 2.57 (d, J = 4.0 Hz, 3H), 2.54 (s, 3H),
		2.03-1.96 (m, 2H), 1.38-1.34 (m, 6H), 0.87-0.84
		(m, 3H), 0.45-0.08 (m, 10H). MS (ESI, m/e)
		[M + 1]+ 602.4
	116	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.19
		(s, 1H), 9.78 (d, J = 8.0 Hz, 1H), 7.58-7.45 (m,
		2H), 7.42-7.28 (m, 1H), 7.14 (d, J = 8.4 Hz,
		1H), 6.76 (s, 1H), 4.58-4.53 (m, 1H), 3.60-3.42
		(m, 4H), 3.25-2.82 (m, 2H), 2.94-2.87 (m, 1H),
		2.58 (d, J = 4.8 Hz, 3H), 2.12-1.65 (m, 7H),
		1.52-1.30 (m, 3H), 0.78-0.68 (m, 6H). MS (ESI,
		m/e) [M + 1]+ 602.4.
	117	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.33
		(s, 1H), 8.53-8.3 (m, 2H), 7.49-7.42 (m, 1H),
		7.42-7.35 (m, 1H), 7.06 (s, 1H), 6.36 (s, 1H),
		4.39-4.36 (m, 1H), 4.02 (s, 3H), 3.46-3.41 (m,
		4H), 3.22-3.16 (m, 2H), 2.98-2.96 (m, 1H),
		2.64-2.60( m, 3H). 1.81-1.67 (m, 8H), 1.21-1.02
		(m, 5H), 1.16-1.14 (m, 6H). MS (ESI, m/e)
		[M + 1]+ 565.5.
	118	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.06
		(s, 1H), 8.41 (d, J = 8.0 Hz, 1H), 7.55-7.29 (m,
		4H), 7.11 (d, J = 8.1 Hz, 1H), 7.05 (s, 1H), 6.74
		(s, 1H), 4.35 (t, J = 8.4 Hz, 1H), 4.02 (s, 3H),
		3.59-3.43 (m, 2H), 3.22-3.12 (m, 3H), 2.94-2.88
		(m, 2H), 2.57 (d, J = 4.2 Hz, 3H), 1.90 (s, 1H),
		1.76 (s, 3H), 1.65 (d, J = 13.2 Hz, 1H), 1.46-
		1.42 (m, 1H), 1.20-1.10 (m, 2H), 0.94 (s, 3H),
		0.82 (s, 9H), 0.74 (d, J = 6.4 Hz, 3H), 0.69 (d,
		J = 6.5 Hz, 3H). MS (ESI) m/e [M + 1]+ 620.4.
	119	1H NMR (400 MHz, DMSO-d6) δ ppm: 9.78 (d,
		J = 4.8 Hz, 1H), 8.42 (d, J = 8.0 Hz, 1H), 7.60-
		7.45 (m, 3H), 7.10 (d, J = 8.0 Hz, 1H), 7.03 (s,
		1H), 6.77 (s, 1H), 4.56-4.48 (m, 1H), 4.03 (s,
		3H), 3.60-3.42 (m, 3H), 3.25-2.82 (m, 4H), 2.58
		(d, J = 4.4 Hz, 3H), 1.90-1.42 (m, 9H), 1.20-
		1.02 (m, 3H), 0.80-0.68 (m, 6H). MS (ESI, m/e)
		[M + 1]+ 582.5.
	120	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.44 (d, J = 8.0 Hz, 1H), 7.55-7.34 (m,
		4H), 7.13 (d, J = 8.0 Hz, 1H), 7.07-7.06 (m,
		1H), 6.29 (s, 1H), 4.82-4.78 (m, 1H), 4.04 (s,
		3H), 3.56-3.45 (m, 2H), 3.19-3.04 (m, 5H), 2.93
		(s, 2H), 2.55 (d, J = 4.0 Hz, 3H), 1.72-1.59 (m,
		3H), 1.53-1.47 (m, 1H), 1.40-1.34 (m, 2H),
		0.87-0.72 (m, 3H), 0.46-0.43 (m, 1H), 0.37-0.34
		(m, 2H), 0.29-0.24 (m, 1H), 0.20-0.16 (m, 2H),
		0.10-0.05 (m, 1H). MS (ESI, m/e) [M + 1]+ 588.5
	121	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.44 (d, J = 8.4 Hz, 1H), 7.45-7.42 (m,
		3H), 7.13-7.10 (m, 4H), 4.39-4.36 (m, 2H), 4.02
		(s, 3H), 3.56-3.51 (s, 5H), 3.46-3.41 (m, 2H),
		3.27-3.21 (m, 1H), 2.89-2.85 (m, 1H), 1.81-1.67
		(m, 13H), 1.55-1.52 (m, 7H), 1.16-1.14 (m,
		2H), 0.84-0.75 (m, 6H). MS (ESI, m/e) [M + 1]+
		677.2.
	122	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.44 (d, J = 8.4 Hz, 1H), 7.45-7.42 (m,
		3H), 7.13-7.10 (m, 4H), 4.39-4.36 (m, 2H), 4.02
		(s, 3H), 3.56-3.51 (s, 5H), 3.46-3.41 (m, 2H),
		3.27-3.21 (m, 1H), 2.89-2.85 (m, 1H), 1.81-1.67
		(m, 14H), 1.55-1.52 (m, 7H), 1.16-1.14 (m,
		1H), 0.84-0.75 (m, 6H). MS (ESI, m/e) [M + 1]+
		677.3.
	123	1H NMR (400 MHz, DMSO-d6) δ ppm: 12.11
		(br, 1H), 8.77 (d, J = 8.8 Hz, 1H), 7.60-7.10 (m,
		4H), 7.08-7.05 (m, 1H), 6.52 (s, 1H), 5.06-4.98
		(m, 1H), 4.02 (s, 3H), 3.65-3.56 (m, 1H), 3.25-
		3.10 (m, 3H), 2.85-2.60 (m, 6H), 2.15-2.03 (m,
		2H), 1.90-1.42 (m, 6H), 1.20-0.92 (m, 5H),
		0.84-0.45 (m, 6H). MS (ESI, m/e) [M + 1]+
		575.7.
	124	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.46 (d, J = 8.4 Hz, 1H), 7.60-7.30 (m,
		4H), 7.10 (d, J = 8.4 Hz, 1H), 7.06 (s, 1H), 6.85
		(s, 1H), 4.45-4.38 (m, 1H), 4.02 (s, 3H), 3.65-
		3.42 (m, 4H), 3.25-2.82 (m, 5H), 1.90-1.42 (m,
		7H), 1.20-0.92 (m, 5H), 0.84-0.70 (m, 12H).
		MS (ESI, m/e) [M + 1]+ 606.5.
	125	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.08
		(s, 1H), 8.47 (d, J = 8.0 Hz, 1H), 7.58-7.30 (m,
		4H), 7.11 (d, J = 8.0 Hz, 1H), 7.06 (s, 1H),
		6.31(s, 1H), 4.40-4.35 (m, 1H), 4.03 (s, 3H),
		3.58-3.48 (m, 2H), 3.25-3.08 (m, 4H), 2.96-2.92
		(m, 2H), 2.55 (d, J = 4.4 Hz, 3H), 2.10-1.56 (m,
		11H), 1.50-1.38 (m, 3H), 1.22-0.95 (m, 5H),
		0.90-0.78 (m, 3H). MS (ESI, m/e) [M + 1]+
		604.4.
	126	MS (ESI, m/e) [M + 1]+ 594.6.
	127	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 8.78 (d, J = 8.2 Hz, 1H), 7.46-7.31 (m,
		7H), 7.16-7.12 (m, 1H), 6.95 (s, 2H), 6.75 (s,
		1H), 4.92-4.89 (m, 1H), 3.95 (s, 3H), 3.57-3.38
		(m, 3H), 3.16-3.12 (m, 3H), 2.90-2.87 (m, 1H),
		2.87-2.85 (m, 1H), 1.49-1.47 (m, 1H), 1.16-1.14
		(m, 2H), 0.81-0.69 (m, 6H). MS (ESI, m/e)
		[M + 1]+ 640.4.
	128	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.23
		(s, 1H), 8.66 (d, J = 8.2 Hz, 1H), 7.51-7.47 (m,
		4H), 7.07-7.00 (m, 6H), 6.76 (s, 1H), 4.52-4.46
		(m, 1H), 4.03 (s, 3H), 3.57-3.38 (m, 2H), 3.16-
		3.12 (m, 3H), 2.90-2.87 (m, 4H), 2.60-2.52 (m,
		4H), 1.84-1.82 (m, 1H), 1.70 (s, 2H), 1.71-1.68
		(m, 1H), 1.49-1.47 (m, 2H), 0.81-0.69 (m, 6H).
		MS (ESI, m/e) [M + 1]+ 612.8.
	129	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.08
		(s, 1H), 8.45 (d, J = 7.8 Hz, 1H), 7.57-7.46 (m,
		2H), 7.40 (s, 1H), 7.36-7.27 (m, 1H), 7.13-7.08
		(m, 1H), 6.95 (d, J = 1.6 Hz, 1H), 6.75 (s, 1H),
		4.45-4.39 (m, 2H), 3.54-3.44 (m, 2H), 3.22-3.11
		(m, 3H), 2.95-2.85 (m, 2H), 2.57 (d, J = 4.4 Hz,
		3H), 1.87-1.79 (m, 2H), 1.75-1.67 (m, 2H),
		1.67-1.51 (m, 2H), 1.51-1.39 (m, 1H), 1.21-1.11
		(m, 4H), 1.10-0.98 (m, 3H), 0.98-0.87 (m, 2H),
		0.71 (dd, J = 19.4, 6.6 Hz, 6H). MS (ESI, m/e)
		[M + 1]+ 590.5.
	130	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.01
		(s, 1H), 8.21 (d, J = 8.3 Hz, 1H), 7.76 (d, J = 1.6
		Hz, 1H), 7.51 (s, 1H), 7.44-7.38 (m, 1H), 7.38-
		7.28 (m, 2H), 7.07 (d, J = 8.2 Hz, 1H), 6.42 (s,
		1H), 4.34 (t, J = 8.6 Hz, 1H), 3.85 (s, 3H), 3.57-
		3.45 (m, 2H), 3.12-2.94 (m, 4H), 2.87 (t, J = 7.8
		Hz, 2H), 2.55 (t, J = 4.6 Hz, 3H), 1.87-1.52 (m,
		6H), 1.24-0.92 (m, 5H), 0.39 (s, 2H), 0.19 (t,
		J = 9.4 Hz, 2H). MS (ESI, m/e) [M + 1]+ 586.4
	131	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.05
		(s, 1H), 8.43 (d, J = 8.4 Hz, 1H), 7.52 (s, 1H),
		7.39-7.24 (m, 2H), 7.12-7.01 (m, 2H), 6.98 (d,
		J = 4.4 Hz, 1H), 6.42 (s, 1H), 4.37 (t, J = 8.6 Hz,
		1H), 3.93 (s, 3H), 3.56-3.38 (m, 2H), 3.15-2.95
		(m, 4H), 2.89-2.79 (m, 2H), 2.56 (d, J = 4.5 Hz,
		3H), 1.91-1.50 (m, 6H), 1.26-0.91 (m, 5H), 0.39
		(s, 2H), 0.18 (q, J = 9.4 Hz, 2H). MS (ESI, m/e)
		[M + 1]+ 586.5
	132	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 8.46 (d, J = 8.0 Hz, 1H), 7.54-7.52 (m,
		2H), 7.37-7.29 (m, 2H), 7.08 (d, J = 8.0 Hz,
		2H), 7.00 (d, J = 4.0 Hz, 1H), 6.42 (s, 1H), 5.21
		(d, J = 4.0 Hz, 1H), 5.15-5.06 (m, 1H), 4.37-
		4.33 (m, 1H), 3.95-3.86 (m, 1H), 3.54-3.43 (m,
		2H), 3.11-2.95 (m, 4H), 2.88-2.84 (m, 2H),
		2.66-2.60 (m, 2H), 2.56 (d, J = 8.0 Hz, 3H),
		2.43-2.33 (m, 2H), 1.87-1.79 (m, 2H), 1.74-1.69
		(m, 2H), 1.62-1.52 (m, 2H), 1.24-1.14 (m, 4H),
		1.02-0.98 (m, 1H), 0.39 (s, 2H), 0.22-0.15 (m,
		2H). MS (ESI, m/e) [M + 1]+ 618.7
	133	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.15
		(s, 1H), 7.90 (d, J = 4.0 Hz, 1H), 7.64 (d, J =
		12.0 Hz, 1H), 7.52 (s, 1H), 7.35-7.32 (m, 1H),
		7.27 (d, J = 8.0 Hz, 1H), 7.09 (d, J = 12.0 Hz,
		1H), 6.69 (d, J = 4.0 Hz, 1H), 6.41 (s, 1H), 5.35
		(d, J = 4.0 Hz, 1H), 4.55-4.51 (m, 1H), 4.48-
		4.40 (m, 1H), 4.02-3.93 (m, 1H), 3.53-3.44 (m,
		2H), 3.11-3.05 (m, 2H), 3.01-2.96 (m, 2H), 2.85
		(s, 2H), 2.79-2.73 (m, 2H), 2.57 (d, J = 4.0 Hz,
		3H), 2.38-2.30 (m, 2H), 1.77-1.61 (m, 6H),
		1.24-1.08 (m, 4H), 1.00-0.97 (m, 1H), 0.39 (s,
		2H), 0.20-0.17 (m, 2H). MS (ESI, m/e) [M + 1]+
		618.6
	134	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 8.47 (d, J = 8.0 Hz, 1H), 7.55-7.45 (m,
		2H), 7.39-7.29 (m, 2H), 7.10-7.06 (m, 2H), 6.32
		(s, 1H), 4.39-4.35 (m, 1H), 4.02 (s, 3H), 3.53-
		3.44 (m, 2H), 3.14-3.08 (m, 3H), 3.04-2.99 (m,
		2H), 2.55 (d, J = 4.0 Hz, 3H), 2.03-1.97 (m,
		1H), 1.87-1.81 (m, 2H), 1.75-1.67 (m, 4H),
		1.62-1.57 (m, 2H), 1.23-1.15 (m, 5H). MS (ESI,
		m/e) [M + 1]+ 536.4
	135	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.08
		(s, 1H), 8.46 (d, J = 8.4 Hz, 1H), 7.56-7.30 (m,
		3H), 7.09 (d, J = 8.4 Hz, 1H), 7.06 (s, 1H), 6.76
		(s, 1H), 4.45-4.38 (m, 1H), 4.02 (s, 3H), 3.68-
		3.42 (m, 3H), 3.25-2.82 (m, 9H), 1.90-1.42 (m,
		7H), 1.20-0.97 (m, 5H), 0.82-0.74 (m, 6H). MS
		(ESI, m/e) [M + 1]+ 578.6.
	136	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.49 (d, J = 8.0 Hz, 1H), 7.56-7.28 (m,
		3H), 7.16-7.08 (m, 2H), 6.77-6.72 (m, 2H),
		5.00-4.79 (m, 1H), 4.42-4.19 (m, 2H), 4.02 (s,
		3H), 3.78-3.42 (m, 5H), 3.25-2.86 (m, 4H),
		1.95-1.55 (m, 9H), 1.50-1.36 (m, 1H), 1.20-0.86
		(m, 5H), 0.82-0.70 (m, 6H). MS (ESI, m/e)
		[M + 1]+ 620.9.
	137	1H NMR (400 MHz, DMSO-d6) δ ppm: 8.78 (d,
		J = 8.0 Hz, 1H), 7.46 (d, J = 2.0 Hz, 1H), 7.35-
		7.25 (m, 3H), 7.08 (s, 1H), 6.40 (s, 1H), 5.09-
		5.02 (m, 1H), 4.05 (s, 3H), 3.68-3.55 (m, 2H),
		3.25-2.82 (m, 6H), 2.56 (d, J = 4.8 Hz, 3H),
		2.15-1.62 (m, 8H), 1.40-1.32 (m, 1H), 0.45-0.14
		(m, 4H). MS (ESI, m/e) [M + 1]+ 559.6.
	138	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.18
		(s, 1H), 9.32 (s, 1H), 7.52-7.25 (m, 3H), 7.12-
		7.06 (m, 1H), 6.65 (s, 1H), 4.57-4.53 (m, 2H),
		3.65-3.30 (m, 4H), 3.28-3.10 (m, 7H), 2.49-2.45
		(m, 3H), 2.01-1.63 (m, 9H), 1.55-1.43 (m, 2H),
		0.78-0.70 (m, 2H), 0.58-0.41 (m, 2H). MS (ESI,
		m/e) [M + 1]+ 600.4
	139	1H NMR (400 MHz, DMSO-d6) δ ppm: 8.75 (d,
		J = 8.8 Hz, 1H), 7.46 (d, J = 6.0 Hz, 1H), 7.40-
		7.30 (m, 3H), 7.07 (s, 1H), 6.29 (s, 1H), 5.07-
		5.02 (m, 1H), 4.01 (s, 3H), 3.68-3.58 (m, 2H),
		3.25-3.06 (m, 6H), 2.95-2.92 (m, 2H), 2.55 (d,
		J = 4.8 Hz, 3H), 2.10-1.56 (m, 8H), 1.40-1.32
		(m, 3H), 1.22-0.85 (m, 7H). MS (ESI, m/e)
		[M + 1]+ 590.6.
	140	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.19-
		10.04 (m, 1H), 8.46 (t, J = 7.2 Hz, 1H), 7.71-
		7.67 (m, 2H), 7.55-7.34 (m, 3H), 7.32-7.18 (m,
		3H), 7.12-7.01 (m, 2H), 6.74 (d, J = 3.0 Hz,
		1H), 4.39 (d, J = 3.6 Hz, 1H), 4.07-4.02 (m,
		3H), 3.73 (d, J = 5.2 Hz, 1H), 3.54-3.45 (m,
		1H), 3.10-3.06 (m, 4H), 2.95 (s, 1H), 2.79-2.73
		(m, 1H), 2.68-2.60 (m, 1H), 2.55 (d, J = 2.6 Hz,
		3H), 1.84 (s, 2H), 1.70 (s, 2H), 1.60 (s, 2H),
		1.19-1.16 (m, 4H), 1.06-0.99 (m, 1H). MS (ESI)
		m/e [M + 1]+ 637.5.
	141	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 8.45 (d, J = 8.4 Hz, 1H), 7.53 (s, 1H),
		7.41 (d, J = 1.8 Hz, 1H), 7.31 (dd, J = 14.2, 6.6
		Hz, 2H), 7.08 (d, J = 8.2 Hz, 1H), 6.96 (d, J =
		1.8 Hz, 1H), 6.42 (s, 1H), 4.45-4.38 (m, 2H),
		3.54-3.43 (m, 2H), 3.11-2.95 (m, 4H), 2.86 (s,
		2H), 2.56 (d, J = 4.6 Hz, 3H), 1.85-1.59 (m,
		6H),1.27-1.11 (m, 4H), 1.06-0.90 (m, 5H), 0.39
		(s, 2H), 0.20-0.16 (m, 2H). MS (ESI, m/e)
		[M + 1]+ 588.5
	142	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.15
		(s, 1H), 8.61 (d, J = 8.8 Hz, 1H), 7.53-7.30 (m,
		4H), 7.09 (d, J = 8.4 Hz, 1H), 7.06 (s, 1H), 6.42
		(s, 1H), 4.53-4.43 (m, 1H), 4.03 (s, 3H), 3.58-
		3.42 (m, 2H), 3.25-2.82 (m, 6H), 2.56 (d, J =
		4.8 Hz, 3H), 2.10-1.62 (m, 8H), 1.50-1.32 (m,
		2H), 0.45-0.14 (m, 4H). MS (ESI, m/e) [M + 1]+
		598.5.
	143	1H NMR (400 MHz, DMSO-d6) δ ppm: 9.93 (s,
		1H), 8.31 (d, J = 8.4 Hz, 1H), 7.38-7.29 (m,
		2H), 7.26-7.10 (m, 2H), 6.93 (d, J = 8.2 Hz,
		1H), 6.91-6.89 (m, 1H), 6.27 (s, 1H), 4.24 (t, J =
		8.4 Hz, 1H), 3.88 (s, 3H), 3.39-3.28 (m, 2H),
		2.98-2.78 (m, 4H), 2.75-2.67 (m, 2H), 2.41 (d,
		J = 4.6 Hz, 3H), 1.83-1.47 (m, 6H), 1.38 (t, J =
		19.4 Hz, 3H), 1.05-0.83 (m, 4H), 0.28-0.21 (m,
		2H), 0.08-0.01 (m, 2H). MS (ESI, m/e) [M + 1]+
		626.4.
	144	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(d, J = 4.4 Hz, 1H), 8.43 (d, J = 8.4 Hz, 1H),
		7.63-7.25 (m, 3H), 7.25-6.91 (m, 3H), 6.57 (s,
		1H), 4.38 (t, J = 8.6 Hz, 1H), 4.03 (s, 3H), 3.82
		(s, 1H), 3.70 (t, J = 14.8 Hz, 1H), 3.44 (s, 1H),
		3.41-3.36 (m, 1H), 3.19-3.12(m, 1H), 3.06-2.95
		(m, 1H), 2.56-2.53 (m, 3H), 1.84-1.70 (m, 6H),
		1.64-1.44 (m, 6H), 1.21-1.10 (m, 4H), 1.05-0.96
		(t, J = 11.8 Hz, 1H). MS (ESI, m/e) [M + 1]+
		562.5
	146	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.46 (d, J = 8.0 Hz, 1H), 7.61 (s, 1H),
		7.43 (s, 2H), 7.18-7.02 (m, 2H), 7.05 (s, 1H),
		4.57 (s, 1H), 4.39-4.37 (m, 2H), 4.03 (s, 3H),
		3.23 (s, 1H), 2.98-2.90 (m, 5H), 1.84-1.82 (m,
		2H), 1.70-1.59 (s, 4H), 1.14-1.02 (m, 3H). MS
		(ESI, m/e) [M + 1]+ 533.4.
	147	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.06
		(s, 1H), 8.44 (d, J = 8.4 Hz, 1H), 7.49-7.42 (m,
		4H), 7.42-7.35 (m, 2H), 6.36 (s, 1H), 4.39-4.36
		(m, 1H), 4.02 (s, 3H), 3.46-3.41 (m, 3H), 3.22-
		3.16 (m, 3H), 2.98-2.96 (m, 3H), 2.64-2.60( m,
		3H).1.81-1.67 (m, 8H), 1.55-1.52 (m, 3H),
		1.16-1.14 (m, 4H). MS (ESI, m/e) [M + 1]+
		590.5.
	148	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.13
		(s, 1H), 8.48 (d, J = 8.0 Hz, 1H), 7.55-7.51 (m,
		1H), 7.47-7.44 (m, 1H), 7.41-7.31 (m, 1H),
		7.11-7.07 (m, 2H), 6.47 (s, 1H), 4.38-4.33 (m,
		1H), 4.04-4.02 (m, 3H), 3.54 (s, 3H), 3.47-3.37
		(m, 2H), 3.19-3.12 (m, 2H), 3.00-2.98 (m, 2H),
		2.86 (s, 2H), 2.01-1.61 (m, 6H), 1.40-1.36 (m,
		2H), 1.02-0.91 (m, 3H), 0.85-0.82 (m, 6H),
		0.46-0.44 (m, 2H), 0.32-0.26 (m, 2H). MS (ESI,
		m/e) [M + 1]+ 605.5
	149	1H NMR (400 MHz, DMSO-d6) δ ppm: 12.23 (s,
		1H), 10.03 (s, 1H), 8.44 (d, J = 8.2 Hz, 1H),
		7.60-7.45 (m, 3H), 7.41-7.35 (m, 2H), 7.10 (d,
		J = 8.6 Hz, 1H), 6.98 (d, J = 8.6 Hz, 1H), 6.74
		(s, 1H), 4.38 (t, J = 8.8 Hz, 1H), 3.59 -- 3.49 (m,
		2H), 3.24-3.16 (m, 2H), 2.90 (t, J = 7.8 Hz, 2H),
		2.57 (d, J = 4.6 Hz, 3H), 2.12-1.82 (m,
		9H),1.78-1.68(m,2H) 1.68-1.61 (m, 5H), 1.52-
		1.42 (m, 2H), 1.19-1.11 (m, 5H), 0.75-0.68 (m,
		6H). MS (ESI, m/e) [M + 1]+ 670.7
	150	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.45 (d, J = 8.4 Hz, 1H), 8.04-8.02 (m,
		1H), 7.57 (s, 0.5H), 7.48 (s, 0.5H), 7.45 (d, J =
		2.0 Hz, 1H), 7.41 (d, J = 8.2 Hz, 0.5H), 7.32 (d,
		J = 7.8 Hz, 0.5H), 7.15-7.12 (m, 3H), 7.06 (d, J =
		2.0 Hz, 1H), 6.85-6.78 (m, 3H), 4.39-4.35 (m,
		1H), 4.23-4.19 (m, 2H), 4.02 (s, 3H), 3.64-3.34
		(m, 4H), 3.21-3.18 (m, 2H), 2.96-2.85 (m, 1H),
		1.85-1.82 (m, 2H), 1.72-1.70 (m, 2H), 1.61-1.58
		(m, 2H), 1.47-1.35 (m, 1H), 1.22-1.18 (m, 5H),
		1.02-0.98 (m, 1H), 0.75-0.68 (m, 6H). MS (ESI,
		m/e) [M + 1]+ 670.6.
	151	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 9.45 (d, J = 3.4 Hz, 1H), 8.44 (d, J = 8.2
		Hz, 1H), 7.62-7.55 (m, 3H), 7.51 (s, 0.5H),
		7.45-7.42 (m, 1H), 7.35-7.24 (m, 3H), 7.16-7.12
		(m, 1H), 7.07-7.00 (m, 2H), 6.92 (s, 1H), 4.42-
		4.36 (m, 1H), 4.03 (s, 3H), 3.77-3.64 (m, 1H),
		3.57-3.38 (m, 3H), 3.16-3.12 (m, 1H), 2.90-2.87
		(m, 1H), 1.84-1.82 (m, 2H), 1.70 (s, 2H), 1.61-
		1.58 (m, 2H), 1.49-1.47 (m, 1H), 1.16-1.14 (m,
		4H), 1.02-1.0 (m, 1H), 0.81-0.69 (m, 6H). MS
		(ESI, m/e) [M + 1]+ 626.5.
	152	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.06
		(s, 1H), 8.43 (d, J = 8.0 Hz, 1H), 7.52-7.45 (m,
		2H), 7.39-7.28 (m, 2H), 7.09-7.06 (m, 2H), 6.41
		(s, 1H), 4.38-4.33 (m, 1H), 4.04-4.02 (m, 3H),
		3.54-3.43 (m, 2H), 3.11-3.05 (m, 2H), 3.00-2.95
		(m, 2H), 2.90-2.82 (m, 2H), 2.56 (d, J = 8.0 Hz,
		3H), 2.03-1.61 (m, 5H), 1.47-1.34 (m, 2H),
		1.23-1.11 (m, 2H), 1.02-0.93 (m, 2H), 0.88-0.82
		(m, 6H), 0.42-0.38 (m, 2H), 0.22-0.17 (m, 2H).
		MS (ESI, m/e) [M + 1]+ 604.7
	153	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07 (s,
		1H), 8.70 (d, J = 8.0 Hz, 1H), 8.37 (s, 1H), 8.19
		(d, J = 7.8 Hz, 1H), 8.01 (d, J = 7.8 Hz, 1H),
		7.69 (t, J = 7.8 Hz, 1H), 7.48 (d, J = 33.8 Hz,
		1H), 7.42-7.25 (m, 2H), 7.07 (d, J = 8.0 Hz,
		1H), 6.41 (s, 1H), 4.43 (s, 1H), 3.53-3.46 (m,
		2H), 3.13-2.99 (m, 4H), 2.85 (s, 2H), 2.56 (d, J =
		4.5 Hz, 3H), 1.95-1.54 (m, 6H), 1.28-1.11 (m,
		5H), 0.39 (s, 2H). 0.20-0.16 (m, 2H). MS (ESI,
		m/e) [M + 1]+ 583.5
	154	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.05 (s,
		1H), 8.43 (d, J = 8.2 Hz, 1H), 7.53-7.43 (m,
		2H), 7.40-7.27 (m, 2H), 7.07 (d, J = 8.2 Hz,
		1H), 7.01 (s, 1H), 6.41 (s, 1H), 4.52-4.47 (m,
		2H), 4.38 (t, J = 8.6 Hz, 1H), 3.66-3.58 (m, 1H),
		3.52-3.48 (m, 2H), 3.2-2.91 (m, 5H), 2.86 (q, J =
		11.8 Hz, 2H), 2.56 (d, J = 4.6 Hz, 3H), 1.89-
		1.52 (m, 6H), 1.22-0.94 (m, 6H), 0.39 (s, 2H),
		0.18 (q, J = 9.2 Hz, 2H). MS (ESI, m/e) [M + 1]+
		576.5
	155	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.08
		(s, 1H), 8.44 (d, J = 8.4 Hz, 1H), 7.46-7.41 (m,
		3H), 7.11-7.06 (m, 2H), 6.97 (s, 1H), 6.80 (d, J =
		8.8 Hz, 1H), 4.39-4.35 (m, 1H), 4.02 (s, 3H),
		3.52-3.43 (m, 2H), 3.39-3.36 (m, 1H), 3.16-3.09
		(m, 1H), 2.94-2.91 (m, 1H), 1.99-1.96 (m, 5H),
		1.88-1.86 (m, 9H), 1.70 (s, 2H), 1.61-1.56 (m,
		9H), 1.15 (s, 3H), 0.85-0.76 (m, 6H). MS (ESI,
		m/e) [M + 1]+ 684.9.
	156	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.08
		(s, 1H), 8.47 (d, J = 8.0 Hz, 1H), 7.50-7.33 (m,
		3H), 7.12-7.06 (m, 2H), 6.18 (s, 1H), 4.42-4.35
		(m, 1H), 4.03 (s, 3H), 3.45-3.36 (m, 2H), 3.25-
		3.07 (m, 9H), 2.95-2.82 (m, 2H), 1.85-2.56 (m,
		6H), 1.22-0.88 (m, 5H), 0.58-0.44 (m, 4H). MS
		(ESI, m/e) [M + 1]+ 549.9.
	157	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.05 (s,
		1H), 8.46 (d, J = 8.2 Hz, 1H), 7.48 (d, J = 33.0
		Hz, 1H), 7.33 (dd, J = 18.6, 13.6 Hz, 2H), 7.08
		(d, J = 8.1 Hz, 1H), 6.92 (d, J = 4.2 Hz, 1H),
		6.64 (d, J = 4.1 Hz, 1H), 6.43 (s, 1H), 4.38 (t, J =
		8.4 Hz, 1H), 3.61-3.40 (m, 3H), 3.13-2.99 (m,
		9H), 2.85 (d, J = 7.2 Hz, 2H), 2.56 (d, J = 4.4
		Hz, 3H), 1.88-1.50 (m, 6H), 1.07-0.81 (m, 5H),
		0.39 (s, 2H), 0.17 (d, J = 13.4 Hz, 2H). MS (ESI,
		m/e) [M + 1]+ 612.5
	158	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 9.11 (d, J = 8.0 Hz, 1H), 8.15 (s, 1H),
		8.06 (d, J = 8.0 Hz, 1H), 7.96 (d, J = 8.0 Hz,
		1H), 7.78-7.74 (m, 1H), 7.34 (d, J = 8.0 Hz,
		1H), 7.25-7.21 (m, 1H), 7.07 (d, J = 8.0 Hz,
		1H), 6.65 (s, 1H), 6.42 (s, 1H), 4.26-4.22 (m,
		1H), 3.54-3.46 (m, 2H), 3.10-2.99 (m, 2H),
		2.90-2.82 (m, 2H), 2.56 (d, J = 4.0 Hz, 3H),
		1.68-1.58 (m, 4H), 1.52-1.43 (m, 4H), 0.40-0.38
		(m, 2H), 0.20-0.15 (m, 2H). MS (ESI, m/e)
		[M + 1]+ 633.7
	159	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.06
		(s, 1H), 8.41 (d, J = 8.0 Hz, 1H), 7.55-7.28 (m,
		3H), 7.22-7.06 (m, 3H), 6.17 (s, 1H), 4.58-4.52
		(m, 1H), 4.01 (s, 3H), 3.65-3.49 (m, 2H), 3.25-
		3.07 (m, 9H), 2.85-2.70 (m, 2H), 0.92-0.78 (m,
		2H), 0.58-0.14 (m, 12H). MS (ESI, m/e)
		[M + 1]+ 561.8.
	160	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.04
		(s, 1H), 8.40 (d, J = 8.0 Hz, 1H), 7.55-7.28 (m,
		3H), 7.10 (d, J = 8.0 Hz, 1H), 6.92 (s, 1H), 6.18
		(s, 1H), 5.55-5.42 (m, 1H), 4.88-4.72 (m, 1H),
		3.65-3.49 (m, 2H), 3.25-3.07 (m, 9H), 2.85-2.70
		(m, 2H), 1.48-1.30 (m, 6H), 0.92-0.78 (m, 2H),
		0.58-0.14 (m, 12H). MS (ESI, m/e) [M + 1]+
		589.7.
	161	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.46 (d, J = 8.2 Hz, 1H), 7.53 (d, J = 9.6
		Hz, 1H), 7.46 (d, J = 1.8 Hz, 1H), 7.41-7.32 (m,
		1H), 7.12 (d, J = 8.2 Hz, 1H), 7.06 (s, 1H), 6.99
		(t, J = 7.8 Hz, 2H), 6.49-6.44 (m, 3H), 6.32 (s,
		1H), 5.86 (t, J = 6.2 Hz, 1H), 4.39 (t, J = 8.6 Hz,
		1H), 4.03 (s, 3H), 3.41-3.19 (m, 4H), 3.16-3.06
		(m, 4H), 2.89-2.74 (m, 2H), 1.88-1.81 (m, 2H),
		1.72-1.70 (m, 2H), 1.63-1.57 (m, 2H), 1.23-1.11
		(m, 4H), 1.04-0.97 (m, 1H), 0.41-0.34 (m, 4H).
		MS (ESI, m/e) [M + 1]+ 611.0.
	162	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.46 (d, J = 8.0 Hz, 1H), 7.58-7.54 (m,
		1H), 7.43-7.41 (m, 2H), 7.18-7.02 (m, 2H), 6.64
		(s, 1H), 4.57 (s, 1H), 4.39-4.37 (m, 1H), 4.03 (s,
		3H), 3.23 (s, 2H), 2.98-2.90 (m, 5H), 1.84-1.82
		(m, 2H), 1.70 (s, 2H), 1.58-1.53 (m, 3H), 1.15
		(s, 3H), 0.88-0.70 (m, 7H). MS (ESI, m/e)
		[M + 1]+ 507.5.
	163	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.12
		(s, 1H), 8.51-8.42 (m, 2H), 8.27 (s, 1H), 7.66-
		7.64 (m, 2H), 7.46-7.43 (m, 2H), 7.36-7.34 (m,
		2H), 7.24-7.18 (m, 1H), 7.14 (d, J = 8.0 Hz,
		1H), 7.06 (s, 1H), 6.91 (s, 1H), 4.44-4.27 (m,
		3H), 4.01 (s, 3H), 3.66-3.48 (m, 2H), 3.22-3.18
		(m, 2H), 2.96-2.93 (m, 1H), 1.83 (s, 2H), 1.68-
		1.63 (m, 5H), 1.47-1.43 (m, 1H), 1.15 (s, 4H),
		1.00 (s, 1H), 0.78-0.70 (m, 6H). MS (ESI, m/e)
		[M + 1]+ 642.2.
	164	1H NMR (400 MHz, DMSO-d6) δ ppm: 9.96 (s,
		1H), 8.34 (d, J = 4.0 Hz, 1H), 7.34-7.25 (m,
		2H), 7.20-7.09 (m, 2H), 6.89-6.87 (m, 2H), 6.23
		(s, 1H), 4.22-4.18 (m, 1H), 3.84-3.83 (m, 3H),
		3.34-3.23 (m, 2H), 2.91-2.85 (m, 2H), 2.83-2.75
		(m, 2H), 2.69-2.63 (m, 2H), 2.36-2.34 (m, 3H),
		2.07-1.98 (m, 1H), 1.81-1.65 (m, 4H), 1.51-1.48
		(m, 1H), 1.09-0.97 (m, 4H), 0.21-0.15 (m, 2H),
		0.04-0.00 (m, 2H). MS (ESI, m/e) [M + 1]+ 630.6
	165	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.06
		(s, 1H), 8.45 (d, J = 8.0 Hz, 1H), 7.48-7.45 (m,
		2H), 7.34 (d, J = 8.0 Hz, 1H), 7.09 (d, J = 8.0
		Hz, 1H), 7.05 (d, J = 4.0 Hz, 1H), 6.18 (s, 1H),
		4.37-4.33 (m, 1H), 4.02 (s, 3H), 3.41 (s, 2H),
		3.22-3.18 (m, 6H), 3.12-3.03 (m, 2H), 2.89-2.82
		(m, 2H), 2.03-1.97 (m, 1H), 1.88-1.74 (m, 4H),
		1.61-1.58 (m, 1H), 1.23-1.11 (m, 5H), 1.06-0.97
		(m, 2H), 0.86-0.82 (m, 3H), 0.56-0.48 (m, 4H).
		MS (ESI, m/e) [M + 1]+ 577.7
	166	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07 (s,
		1H), 8.40 (d, J = 8.8 Hz, 1H), 7.55-7.45 (m,
		3H), 7.41-7.30 (m, 1H), 7.11 (d, J = 8.4 Hz, 1H),
		7.05 (s, 1H), 6.71 (s, 1H), 4.79 (t, J = 9.0 Hz,
		1H), 4.04 (s, 3H), 3.58-3.51 (m, 2H), 3.47-3.37
		(m, 2H), 3.31-3.21 (m, 2H), 2.91-2.86 (m, 1H),
		2.58 (d, J = 3.0 Hz, 3H), 2.06-1.92 (m, 1H),
		1.41-1.31 (m, 3H), 0.87-0.76 (m, 5H), 0.42-0.19
		(m, 8H). MS (ESI, m/e) [M + 1]+ 562.5
	167	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.01,
		(s, 1H), 8.02 (s, 1H), 7.59 (d, J = 4.4 Hz, 1H),
		7.47 (s, 1H), 7.38-7.25 (m, 2H), 7.09 (d, J = 8.2
		Hz, 1H), 6.43 (s, 1H), 4.47 (s, 1H), 3.92 (s, 2H),
		3.58-3.38 (m, 2H), 3 .. 18-3.11 (m, 5H), 2.86 (s,
		2H), 2.55 (d, J = 4.8 Hz, 3H), 1.81-1.52 (m,
		6H), 1.28-1.12 m, 6H), 0.40 (s, 2H), 0.21-0.17
		(m, 2H). MS (ESI, m/e) [M + 1]+ 580.5
	168	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.48 (d, J = 8.2 Hz, 1H), 7.48 (t, J =
		16.4 Hz, 2H), 7.41-7.25 (m, 2H), 7.07 (d, J =
		12.4 Hz, 2H), 6.43 (s, 1H), 4.37 (t, J = 8.4 Hz,
		1H), 4.02 (s, 3H), 3.56-3.40 (m, 3H), 3.11-2.95
		(m, 4H), 2.91-2.80 (m, 2H), 2.56 (d, J = 4.4 Hz,
		3H), 2.23-2.09 (m, 2H), 1.87-1.78 (m, 4H),
		1.61-1.52 (m, 2H), 1.22-1.16 (m, 1H), 1.11-0.98
		(m, 2H), 0.44-0.36 (m, 2H), 0.21-0.13 (m, 2H).
		MS (ESI, m/e) [M + 1]+ 644.5.
	169	1H NMR (400 MHz, DMSO-d6) δ ppm: 12.20-
		11.97 (m, 1H), 10.07 (s, 1H), 8.42 (d, J = 8.2
		Hz, 1H), 7.54-7.50 (m, 4H), 7.35-7.30 (m, 1H),
		7.16-7.13 (m, 3H), 7.04 (s, 1H), 6.77 (s, 1H),
		4.38-4.36 (m, 1H), 4.03-3.84 (m, 5H), 3.64-3.52
		(m, 3H), 3.25-3.11 (m, 2H), 1.82 (s, 2H), 1.65-
		1.58 (m, 4H), 1.45-1.44 (m, 1H), 1.18-0.93 (m,
		5H), 0.76-0.72 (m, 6H). MS (ESI, m/e) [M + 1]+
		623.6.
	171	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.50 (d, J = 8.0 Hz, 1H), 7.54-7.45 (m,
		2H), 7.40-7.29 (m, 2H), 7.10-7.06 (m, 2H), 6.43
		(s, 1H), 4.38-4.33 (m, 1H), 4.03 (s, 3H), 3.53-
		3.42 (m, 2H), 3.11-2.95 (m, 2H), 2.89-2.82 (m,
		2H), 2.56 (d, J = 4.0 Hz, 3H), 1.88-1.75 (m,
		4H), 1.61-1.57 (m, 1H), 1.23-1.11 (m, 5H),
		1.06-0.97 (m, 2H), 0.90-0.77 (m, 3H), 0.43-0.36
		(m, 2H), 0.21-0.15 (m, 2H). MS (ESI, m/e)
		[M + 1]+ 590.5
	172	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.12
		(s, 1H), 8.49 (d, J = 8.2 Hz, 1H), 7.54 (d, J =
		10.2 Hz, 1H), 7.45 (d, J = 1.4 Hz, 1H), 7.37 (dd,
		J = 13.2, 8.4 Hz, 1H), 7.12 (d, J = 8.2 Hz, 1H),
		7.06 (s, 1H), 6.95 (dd, J = 12.2, 7.8 Hz, 1H),
		6.86 (t, J = 7.8 Hz, 1H), 6.58 (t, J = 8.6 Hz, 1H),
		6.49-6.44 (m, 2H), 5.99 (s, 1H), 4.38 (t, J = 8.4
		Hz, 1H), 4.02 (s, 3H), 3.44-3.40 (m, 2H), 3.26-
		3.07 (m, 6H), 2.90-2.78 (m, 2H), 1.88-1.80 (m,
		2H), 1.72-1.69 (m, 2H), 1.62-1.55 (m, 2H),
		1.20-1.12 (m, 4H), 1.05-0.92 (m, 1H), 0.44-0.38
		(m, 4H). MS (ESI, m/e) [M + 1]+ 628.5.
	173	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 8.47 (d, J = 8.4 Hz, 1H), 7.52 (d, J =
		10.4 Hz, 1H), 7.46 (s, 1H), 7.41-7.33 (m, 1H),
		7.12 (d, J = 8.0 Hz, 1H), 7.06 (s, 1H), 6.75 (d,
		J = 7.8 Hz, 1H), 6.66 (t, J = 7.4 Hz, 1H), 6.48 (t,
		J = 7.6 Hz, 1H), 6.41 (s, 1H), 6.35 (d, J = 7.8Hz,
		1H), 5.33 (d, J = 4.6 Hz, 1H), 4.38 (t, J = 8.6
		Hz, 1H), 4.02 (s, 3H), 3.73 (s, 3H), 3.20-3.12
		(m, 6H), 2.87 (s, 2H), 2.04-1.94 (m, 2H), 1.86-
		1.80 (m, 2H), 1.72-1.69 (m, 2H), 1.62-1.59 (m,
		2H), 1.17-1.14 (s, 4H), 0.85 (t, J = 6.0 Hz, 1H),
		0.49 (d, J = 9.2 Hz, 4H). MS (ESI, m/e) [M + 1]+
		640.5.
	174	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10 (s,
		1H), 8.46 (d, J = 8.2 Hz, 1H), 8.23 (s, 1H), 7.54
		(d,J = 6.8 Hz, 1H), 7.46 (s, 1H), 7.37 (d, J = 4.6
		Hz, 1H), 7.11 (d, J = 8.0 Hz, 1H), 7.06 (s, 1H),
		6.48 (s, 1H), 4.38 (d, J = 4.2 Hz, 1H), 4.02 (s,
		3H), 3.55-3.44 (m, 2H), 3.25 (s, 1H), 3.11-3.07
		(m, 2H), 3.02 (s, 1H), 2.65 (d, J = 14.8 Hz, 2H),
		2.55 (d, J = 4.4 Hz, 3H), 2.37-2.24 (m, 2H),
		2.20-2.01 (m, 2H), 1.83 (s, 2H), 1.69 (s, 2H),
		1.59 (d, J = 18.8 Hz, 2H), 1.15 (s, 4H), 1.05-
		0.98 (m, 1H). MS (ESI) m/e [M + 1]+ 612.5.
	175	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 8.47 (d, J = 8.2 Hz, 1H), 8.03 (s, 1H),
		7.60-7.20 (m, 5H), 7.17-7.02 (m, 4H), 6.59 (s,
		1H), 4.43-4.26 (m, 3H), 4.03 (s, 3H), 3.65-3.54
		(m, 2H), 3.23-2.96 (m, 4H), 2.89-2.85 (m, 2H),
		1.83-1.82 (m, 2H), 1.70 (s, 2H), 1.59-1.56 (m,
		2H), 1.15 (s, 4H), 0.39 (s, 2H), 0.21-0.18 (m,
		2H). MS (ESI, m/e) [M + 1]+ 656.5.
	176	MS (ESI, m/e) [M + 1]+ 636.7
	177	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 8.42 (d, J = 8.8 Hz, 1H), 7.59 (s, 1H),
		7.52-7.46 (m, 2H), 7.34 (d, J = 8.8 Hz, 1H), 7.17
		(d, J = 8.4 Hz, 1H), 6.93 (d, J = 1.8 Hz, 1H),
		5.48-5.34 (m, 1H), 4.82-4.78 (m, 1H), 4.66-4.54
		(m, 1H), 4.31 (s, 1H), 3.50-3.47 (m, 1H), 3.17-
		3.15 (m, 1H), 3.03-2.98 (m, 2H), 2.88-2.80 (m,
		2H), 1.39-1.34 (m, 6H), 0.93-0.68 (m, 3H),
		0.45-0.07 (m, 8H). MS (ESI, m/e) [M + 1]+
		573.6.
	178	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.22
		(s, 1H), 9.23 (d, J = 8.0 Hz, 1H), 7.60 (s, 1H),
		7.48 (s, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.18 (d,
		J = 8.0 Hz, 1H), 4.59-4.56 (m, 2H), 4.32 (s, 1H),
		3.50-3.46 (m, 1H), 3.16-3.12 (m, 1H), 3.04-3.0
		(m, 2H), 2.95-2.86 (m, 3H), 2.47 (s, 3H), 2.04
		(s, 3H), 1.93-1.64 (m, 4H), 1.52-1.27 (m, 2H).
		MS (ESI, m/e) [M + 1]+ 571.5.
	179	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.48 (d, J = 8.2 Hz, 1H), 7.60-7.23 (m,
		4H), 7.11 (d, J = 8.2 Hz, 1H), 7.07 (s, 1H), 6.68
		(s, 1H), 4.38 (t, J = 8.4 Hz, 1H), 4.03 (s, 3H),
		3.69-3.46 (m, 3H), 3.27 (d, J = 12.2 Hz, 1H),
		3.15-3.08 (m, 3H), 2.91 (d, J = 9.8 Hz, 1H), 2.55
		(d, J = 4.4 Hz, 3H), 1.86-1.81 (m, 2H), 1.72-
		1.69 (m, 2H), 1.62-1.54 (m, 2H), 1.18-1.12 (m,
		4H), 1.06-0.94 (m, 1H), 0.88 (d, J = 6.4 Hz,
		3H). MS (ESI, m/e) [M + 1]+ 618.5.
	180	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.14 (s,
		1H), 9.68 (d, J = 7.0 Hz, 1H), 8.76 (d, J = 8.4
		Hz, 1H), 8.72 (s, 1H), 8.17 (d, J = 7.2 Hz, 1H),
		7.50 (s,1H), 7.34-7.24 (m, 3H), 7.08 (d, J = 8.0
		Hz, 1H), 6.43 (s, 1H), 4.48 (t, J = 9.0 Hz,1H),
		3.56-3.46 (m, 2H), 3.12-2.91 (m, 4H), 2.85 (s,
		2H), 2.55 (d, J = 4.6 Hz, 3H), 1.95-1.55 (m,
		6H), 1.29-0.93 (m, 5H), 0.39 (s, 2H), 0.24-0.07
		(m, 2H). (ESI, m/e) [M + 1]+ 623.6
	181	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.16
		(s, 1H), 9.13-9.11 (m, 1H), 7.52-7.43 (m, 1H),
		7.40-7.26 (m, 2H), 7.09 (d, J = 8.0 Hz, 1H), 6.44
		(s, 1H), 4.49-4.45 (m, 1H), 3.54-3.43 (m, 2H),
		3.11-3.05 (m, 2H), 3.01-2.98 (m, 2H), 2.89-2.84
		(m, 2H), 2.56 (d, J = 4.0 Hz, 3H), 2.48 (s, 3H),
		2.27-2.15 (m,1H), 2.01-1.84 (m, 4H), 1.74-1.68
		(m, 1H), 1.23-1.16 (m, 4H), 0.43-0.36 (m, 2H),
		0.21-0.15 (m, 2H). MS (ESI, m/e) [M + 1]+ 632.6
	182	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.47 (d, J = 7.8 Hz, 1H), 7.96 (s, 1H),
		7.53 (s, 1H), 7.46-7.43 (m, 1H), 7.33 (d, J = 8.8
		Hz, 1H), 7.09-7.06 (m, 2H), 6.56 (s, 1H), 4.39-
		4.35 (m, 1H), 4.03 (s, 3H), 3.50-3.45 (m, 2H),
		3.12-2.78 (m, 8H), 2.35 (s, 1H), 1.94 (s, 6H),
		1.83 (s, 2H), 1.72-1.70 (m, 2H), 1.63-1.60 (m,
		2H), 1.16-1.10 (s, 3H), 0.42 (s, 2H), 0.25-0.18
		(m, 2H). MS (ESI, m/e) [M + 1]+ 614.5.
	183	1H NMR (400 MHz, DMSO-d6) δ ppm: 9.99 (s,
		1H), 8.91 (d, J = 8.0 Hz, 1H), 7.44 (s, 1H), 7.35
		(s, 1H), 7.18 (d, J = 12.0 Hz, 1H), 7.05 (d, J =
		12.0 Hz, 1H), 4.74-4.70 (m, 1H), 4.48-4.45 (m,
		1H), 4.24-4.14 (m, 1H), 3.38-3.33 (m, 1H),
		3.04-3.00 (m, 1H), 2.91-2.85 (m, 2H), 2.79-2.73
		(m, 1H), 2.70-2.65 (m,1H), 2.35 (s, 3H), 0.74-
		0.58 (m, 3H), 0.35-0.30 (m, 1H), 0.27-0.23 (m,
		1H), 0.21-0.01 (m, 6H). MS (ESI, m/e) [M + 1]+
		547.4
	184	1H NMR (400 MHz, DMSO-d6) δ ppm: 11.94
		(s, 1H), 10.17 (s, 1H), 9.22 (d, J = 8.0 Hz, 1H),
		7.55-7.22 (m, 4H), 7.15 -7.04 (m, 3H), 6.41 (s,
		1H), 4.56-4.48 (m, 1H), 4.19-4.07 (m, 2H),
		3.49-3.36 (m, 2H), 3.30-3.22 (m, 2H), 2.96-2.87
		(m, 2H), 2.48 (s, 3H), 2.10-1.60 (m, 7H), 1.50-
		1.30 (m, 2H), 0.48-0.34 (m, 4H). MS (ESI, m/e)
		[M + 1]+ 659.5.
	185	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.19
		(s, 1H), 9.24 (d, J = 8.0 Hz, 1H), 7.55-7.26 (m,
		3H), 7.11 (d, J = 8.0 Hz, 1H), 6.67 (s, 1H), 4.58-
		4.50 (m, 1H), 3.58 (t, J = 17.2 Hz, 2H), 3.18-
		2.97 (m, 5H), 2.93-2.83 (m, 3H), 2.48 (s, 3H),
		2.10-1.65 (m, 8H), 1.59-1.30 (m, 7H), 1.19-0.95
		(m, 6H), 0.50-0.28 (m, 4H). MS (ESI, m/e)
		[M + 1]+ 710.6.
	186	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.22
		(d, J = 11.8 Hz, 1H), 8.66 (d, J = 8.2 Hz, 1H),
		7.59-7.38 (m, 3H), 7.37 (d, J = 25.8 Hz, 1H),
		7.20-7.04 (m, 5H), 6.78 (s, 1H), 4.55 (t, J = 8.8
		Hz, 1H), 4.04 (s, 3H), 3.58-3.46 (m, 2H), 3.33-
		3.29 (m, 3H), 3.23-3.08 (m, 2H), 2.91-2.79 (m,
		2H), 2.79-2.69 (m, 2H), 2.57 (d, J = 4.2 Hz,
		3H), 2.38-2.28 (m, 1H), 1.99-1.88 (m , 1H),
		1.48-1.38 (m, 2H), 0.72 (dd, J = 19.4, 6.2 Hz,
		6H). MS (ESI, m/e) [M + 1]+ 646.5
	187	1H NMR (400 MHz, DMSO-d6) δ ppm: 12.32
		(d, J = 12.6 Hz, 1H), 10.19 (s, 1H), 9.21 (d, J =
		8.6 Hz, 1H), 7.59-7.49 (m, 1H), 7.42-7.22 (m,
		2H), 7.15 (d, J = 8.6 Hz, 2H), 6.93 (s, 1H), 6.44
		(s, 1H), 4.52 (t, J = 8.4 Hz, 1H), 4.14-4.00 (m,
		2H), 3.56-3.49 (m, 2H) 3.27 (s, 2H), 2.87 (s,
		2H), 2.46 (s, 3H), 2.05-2.01 (m, 3H), 1.85-1.61
		(m, 4H), 1.43-1.28 (m, 2H), 0.44-0.39 (m, 4H).
		MS (ESI, m/e) [M + 1]+678.1
	188	1H NMR (400 MHz, DMSO-d6) δ ppm: 12.05
		(s, 1H), 10.20 (s, 1H), 9.24 (d, J = 8.0 Hz, 1H),
		7.55-7.26 (m, 2H), 7.12 (d, J = 8.0 Hz, 1H), 6.45
		(s, 1H), 4.58-4.50 (m, 1H), 3.49-3.36 (m, 2H),
		3.20-3.12 (m, 2H), 3.06-2.97 (m, 2H), 2.86 (s,
		2H), 2.48 (s, 3H), 2.10-1.65 (m, 7H), 1.50-1.30
		(m, 2H), 0.50-0.24 (m, 4H). MS (ESI, m/e)
		[M + 1]+ 587.6.
	189	1H NMR (400 MHz, DMSO-d6) δ ppm: 12.03
		(s, 1H), 10.10 (s, 1H), 8.47 (d, J = 8.4 Hz, 1H),
		7.54 (s, 1H), 7.45 (s, 1H), 7.39 (d, J = 7.4 Hz,
		OH), 7.30 (d, J = 8.0 Hz, 0.5H), 7.12-7.01 (m,
		2H), 6.44 (s, 1H), 4.39-4.36 (m, 1H), 4.03 (s,
		3H), 3.46-3.40 (m, 1H), 3.16-3.14 (m, 2H),
		3.10-3.01 (m, 2H), 2.86-2.84 (m, 2H), 1.84-1.80
		(m, 2H), 1.72-1.70 (m, 2H), 1.63-1.60 (m, 2H),
		1.19-1.10 (m, 6H), 0.43 (s, 2H), 0.29-0.21 (m,
		2H). MS (ESI, m/e) [M + 1]+ 549.5.
	190	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.19
		(s, 1H), 9.22 (d, J = 8.2 Hz, 1H), 7.52-7.43 (m,
		2H), 7.38 (d, J = 8.6 Hz, 0.5H), 7.28 (d, J = 8.2
		Hz, 0.5H), 7.11 (d, J = 8.0 Hz, 1H), 6.59 (s, 1H),
		4.56-4.51 (m, 1H), 4.19-4.06 (m, 1H), 3.57-3.43
		(m, 2H), 3.10-3.01 (m, 5H), 2.89-2.86 (m, 3H),
		2.47 (s, 2H), 2.34-2.30 (m, 1H), 2.08-1.97 (m,
		5H), 1.87 (s, 1H), 1.70-1.65 (m, 2H), 1.49-1.20
		(m, 3H), 0.42 (s, 2H), 0.40 -0.20 (m, 2H). MS
		(ESI, m/e) [M + 1]+ 690.6.
	191	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.19
		(s, 1H), 9.23 (d, J = 8.4 Hz, 1H), 7.55-7.32 (m,
		3H), 7.10-7.05 (m, 1H), 6.62 (s, 1H), 4.56-4.51
		(m, 1H), 3.56-3.51 (s, 3H), 3.27-2.95 (m, 4H),
		2.89-2.85 (m, 1H), 2.47 (s, 1H), 1.95-1.67 (m,
		14H), 1.55-1.42 (m, 4H), 0.45-0.43 (m, 2H),
		0.34-0.25 (m, 2H). MS (ESI, m/e) [M + 1]+
		704.6.
	192	1H NMR (400 MHz, DMSO-d6) δ ppm: 12.49
		(s, 1H), 10.19 (s, 1H), 9.21 (d, J = 8.0 Hz, 1H),
		7.69 (d, J = 8.6 Hz, 1H), 7.57-7.50(m, 1H), 7.42
		(d, J = 7.6 Hz, 1H), 7.39-7.23 (m, 2H), 7.15 (d,
		J = 8.2 Hz, 1H), 6.39 (s, 1H), 4.52 (t, J = 8.2 Hz,
		1H), 4.14-4.02 (m, 2H), 3.45 (s, 2H), 2.86 (s,
		2H), 2.69 (s, 2H), 2.46 (s, 3H), 2.00 (d, J = 7.6
		Hz, 4H), 1.89-1.62 (m, 5H), 1.48-1.29 (m, 4H).
		MS (ESI) m/e [M + 1]+ 727.7.
	193	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.19
		(s, 1H), 8.54 (d, J = 8.0 Hz, 1H), 7.63-7.44 (m,
		2H), 7.43-7.33 (m, 1H), 7.25 (s, 1H), 7.14 (d, J =
		8.4 Hz, 1H), 7.07 (s, 1H), 4.36 (t, J = 8.6 Hz,
		1H), 4.02 (s, 3H), 3.52-3.42 (m, 2H), 3.17-3.06
		(m, 2H), 2.92-2.85 (m, 4H), 1.87-1.82 (m, 2H),
		1.72-1.69 (m, 2H), 1.62-1.57 (m, 2H), 1.18-1.11
		(m, 4H), 1.06-0.94 (m, 1H), 0.51 (d, J = 9.6 Hz,
		4H). MS (ESI, m/e) [M + 1]+ 601.4.
	194	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.15
		(s, 1H), 8.52 (d, J = 8.2 Hz, 1H), 7.61-7.45 (m,
		2H), 7.38 (dt, J = 15.8, 8.2 Hz, 1H), 7.13 (dd, J =
		7.8, 4.4 Hz, 1H), 7.07 (s, 1H), 6.72 (d, J = 15.6
		Hz, 1H), 4.69 (s, 1H), 4.38 (t, J = 8.6 Hz, 1H),
		4.03 (s, 3H), 3.53-3.35 (m, 3H), 3.26-3.03 (m,
		3H), 2.95-2.72 (m, 2H), 2.70-2.57 (m, 1H),
		1.86-1.81 (m, 2H), 1.72-1.69 (m, 2H), 1.62-1.54
		(m, 2H), 1.18-1.12 (m, 4H), 1.04-0.96 (m, 1H),
		0.38-0.32 (m, 2H), 0.21-0.07 (m, 2H). MS (ESI,
		m/e) [M + 1]+ 603.4.
	195	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.46 (d, J = 4.0 Hz, 1H), 7.62-7.58 (m,
		1H), 7.49 (s, 2H), 7.38-7.33 (m, 1H), 7.17 (d, J =
		8.0 Hz, 1H), 6.95 (s, 1H), 5.42-5.36 (m, 1H),
		4.61-4.58 (m, 1H), 4.38-4.28 (m, 2H), 3.50-3.45
		(m, 1H), 3.16-3.11 (m, 1H), 3.04-2.98 (m, 2H),
		2.91-2.85 (m, 1H), 2.82-2.77 (m,1H), 1.89-1.77
		(m, 2H), 1.77-1.67 (m, 2H), 1.62-1.55 (m, 2H),
		1.37-1.33 (m, 6H), 1.23-1.15 (m, 4H), 1.02-0.97
		(m, 1H). MS (ESI, m/e) [M + 1]+ 561.5
	196	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.22
		(d, J = 12.6 Hz, 1H), 8.66 (d, J = 7.4 Hz, 1H),
		7.46 (t, J = 8.8 Hz, 4H), 7.20-7.06 (m, 5H), 6.78
		(s, 1H), 4.55 (s, 1H), 4.09-4.04 (m, 2H), 3.61-
		3.45 (m, 2H), 3.24-3.02 (m, 4H), 2.88-2.78 (m,
		5H), 2.57 (s, 3H), 2.45-2.35 (m, 2H), 2.05-1.99
		(m, 1H), 1.49-1.42 (m, 2H), 0.79-0.66 (m, 6H).
		MS (ESI, m/e) [M + 1]+ 646.4
	197	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 8.43 (d, J = 8.0 Hz, 1H), 7.59-7.52 (m,
		1H), 7.47 (s, 2H), 7.40-7.33 (m, 1H), 7.17 (d, J =
		8.0 Hz, 1H), 7.05 (d, J = 4.0 Hz, 1H), 4.82-
		4.78 (m, 1H), 4.61-4.58 (m, 1H), 4.38-4.28 (m,
		1H), 4.01 (s, 3H), 3.51-3.46 (m, 1H), 3.16-2.98
		(m, 3H), 2.94-2.78 (m, 2H), 0.87-0.73 (m, 3H),
		0.46-0.43 (m, 1H), 0.39-0.34 (m, 2H), 0.30-0.26
		(m, 1H), 0.22-0.18 (m, 3H), 0.11-0.07 (m, 1H).
		MS (ESI, m/e) [M + 1]+ 545.6
	198	1H NMR (400 MHz, DMSO-d6) δ ppm: 12.48
		(s, 1H), 10.06 (d, J = 5.6 Hz, 1H), 8.39 (d, J =
		8.6 Hz, 1H), 7.69 (d, J = 7.8 Hz, 1H), 7.50-7.38
		(m, 3H), 7.33-7.22 (m, 2H), 7.14 (d, J = 8.2 Hz,
		1H), 6.91 (s, 1H), 6.38 (s, 1H), 5.41-5.36 (m,
		1H), 4.76 (t, J = 8.2 Hz, 1H), 4.14-3.95 (m, 2H),
		3.49-3.40 (m, 2H), 2.86 (s, 2H), 2.69 (s, 2H),
		1.36 (d, J = 6.6 Hz, 3H), 1.33 (d, J = 6.6 Hz,
		3H), 1.23 (s, 1H), 0.86-0.67 (m, 4H), 0.34 (s,
		3H), 0.28 (d, J = 8.8 Hz, 1H), 0.18 (s, 3H), 0.07
		(s, 1H). MS (ESI) m/e [M + 1]+ 729.5.
	199	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 8.47-8.45(m, 1H), 7.57-7.54 (m, 2H),
		7.34-7.29 (m, 1H), 7.09-7.05 (m, 2H), 6.34 (s,
		1H), 4.35-4.30 (m, 1H), 4.03 (s, 1H), 2.89-2.85
		(m, 6H), 2.05-2.01 (m, 2H), 1.91-1.63 (m, 4H),
		1.49-1.20 (m, 3H), 0.45 (s, 4H). MS (ESI, m/e)
		[M + 1]+ 505.6.
	200	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.12
		(s, 1H), 9.45 (s, 1H), 8.47-8.45(m, 1H), 7.57-
		7.54 (m, 2H), 7.48-7.39 (m, 2H), 7.35-7.30 (m,
		3H), 6.86-6.84 (m, 3H), 6.64 (s, 1H), 4.35-4.30
		(m, 1H), 4.03 (s, 1H),3.70-3.54 (m, 2H), 3.24-
		3.03 (m, 5H), 2.89-2.85 (m, 2H), 2.05-2.01 (m,
		3H), 1.91-1.63 (m, 4H), 1.49-1.20 (m, 3H), 0.45
		(s, 2H), 0.30-0.20 (m, 2H). MS (ESI, m/e)
		[M + 1]+ 642.8.
	201	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.26-
		10.21 (m, 1H), 8.68 (d, J = 8.6 Hz, 1H), 7.6-
		7.25 (m, 4H), 7.24 (d, J = 7.2 Hz, 1H), 7.18-
		6.97 (m, 4H), 6.78 (s, 1H), 4.55 (s, 1H), 4.05 (s,
		3H), 3.60-3.45 (m, 2H), 3.24-3.12 (m, 3H), 2.90
		(s, 3H), 2.70 (d, J = 26.4 Hz,2H), 2.57 (d, J =
		4.2 Hz, 3H), 2.35-2.32 (m, 2H), 2.05-2.02 (m,
		1H), 1.62-1.33 (m, 2H), 0.77-0.52 (m, 6H). MS
		(ESI, m/e) [M + 1]+ 646.4
	202	MS (ESI) m/e [M + 1]+ 590.4.
	203	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.22
		(s, 1H), 9.47 (s, 1H), 9.24 (d, J = 8.0 Hz, 1H),
		7.57 (s, 2H), 7.54 (s, 1H), 7.48-7.39 (m, 1H),
		7.35-7.30 (m, 3H), 7.15 (d, J = 8.0 Hz, 1H),
		6.86-6.84 (m, 1H), 6.64 (s, 1H), 4.55-4.52 (m,
		1H), 3.70-3.54 (m, 2H), 3.24-3.03 (m, 5H),
		2.89-2.85 (m, 2H), 2.47 (s, 3H), 2.05-2.01 (m,
		3H), 1.91-1.63 (m, 4H), 1.49-1.20 (m, 4H), 0.45
		(s, 2H), 0.30-0.20 (m, 2H).
	204	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.16
		(s, 1H), 8.75 (d, J = 8.2 Hz, 1H), 7.54-7.52 (m,
		1H), 7.45-7.35(m, 6H), 7.13 (d, J = 8.2 Hz, 1H),
		6.95 (s, 1H), 6.77 (s, 1H), 4.78 (s, 1H), 3.94 (s,
		3H), 3.58-3.44 (m, 2H), 3.22-3.10 (m, 3H),
		3.04-2.80 (m, 2H), 2.59-2.54 (m, 3H), 1.47-1.40
		(m, 1H), 1.29-1.26 (m, 5H), 0.77-0.67 (m, 6H).
		MS (ESI, m/e) [M + 1]+ 606.5.
	205	1H NMR (400 MHz, DMSO-d6) δ ppm: 11.69
		(s, 1H), 10.16 (s, 1H), 9.21 (d, J = 8.0 Hz, 1H),
		7.69 (d, J = 7.6 Hz, 1H), 7.65-7.47 (m, 2H),
		7.37-7.20 (m, 4H), 7.15-7.07 (m, 2H), 6.34 (s,
		1H), 4.58-4.47 (m, 1H), 4.17-4.05 (m, 2H),
		3.28-3.20 (m, 4H), 2.86 (s, 2H), 2.48 (s, 3H),
		2.10-1.60 (m, 8H), 1.50-1.30 (m, 2H), 0.50-0.40
		(m, 4H). MS (ESI, m/e) [M + 1]+ 685.7.
	206	1H NMR (400 MHz, DMSO-d6) δ ppm: 11.68
		(s, 1H), 10.02 (s, 1H), 8.40 (d, J = 8.6 Hz, 1H)
		7.64-7.52 (m, 2H), 7.50-7.35 (m, 4H), 7.30-7.14
		(m, 2H), 6.91 (s, 1H), 6.33 (s, 1H), 4.77-4.74
		(m, 1H), 4.10-4.04 (m, 1H), 3.65-3.40 (m, 4H),
		2.91-2.84 (m, 2H), 1.40-1.33 (m, 6H), 0.89-0.70
		(m, 3H), 0.45-0.11 (m, 12H). MS (ESI, m/e)
		[M + 1]+ 687.6
	207	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.18
		(s, 1H), 9.32 (s, 1H), 7.52-7.25 (m, 2H), 7.12-
		7.06 (m, 1H), 6.65 (s, 1H), 4.57-4.53 (m, 2H),
		3.65-3.30 (m, 3H), 3.28-3.10 (m, 2H), 2.89-2.80
		(m, 2H), 2.49-2.45 (m, 3H), 2.01-1.63 (m, 7H),
		1.55-1.43 (m, 5H), 0.78-0.70 (m, 6H), 0.58-0.41
		(m, 4H), MS (ESI, m/e) [M + 1]+ 657.7
	208	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.23-
		10.18 (m, 1H), 9.33-9.29 (m, 1H), 7.57-7.42 (m,
		3H), 7.12-7.01 (s, 4H), 4.57-4.53 (m, 2H), 4.32-
		4.30 (m, 1H), 3.65-3.30 (m, 2H), 3.28-3.10 (m,
		5H), 2.85-2.80 (m, 3H), 2.35-2.30 (m, 1H),
		1.87-1.83 (m, 1H), 1.55-1.23 (m, 5H). MS (ESI,
		m/e) [M + 1]+ 617.3
	209	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 8.44 (d, J = 8.4 Hz, 1H), 7.85-7.80 (m,
		1H), 7.58-7.50 (m, 2H), 7.32-7.28 (s, 1H), 7.11-
		6.98 (m, 3H), 4.47-4.43 (m, 1H), 4.05 (s, 3H),
		3.61-3.56 (m, 1H), 3.24-3.22 (m, 4H), 3.10-3.05
		(m, 4H), 2.49-2.28 (m, 1H), 1.95-1.65 (m, 5H),
		1.82-1.58 (m, 3H), 1.24-1.20 (m, 5H), 0.89-0.79
		(m, 5H). MS (ESI, m/e) [M + 1]+ 506.4.
	210	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.30
		(s, 1H), 9.27 (d, J = 8.0 Hz, 1H), 7.64-7.55 (m,
		1H), 7.48-7.37 (m, 1H), 7.24 (d, J = 8.4 Hz,
		1H), 6.87 (s, 1H), 4.58-4.53 (m, 1H), 3.75-3.64
		(m, 2H), 3.28-3.23 (m, 2H), 3.16 (s, 2H), 2.93
		(s, 2H), 2.48 (s, 3H), 2.10-1.64 (m, 7H), 1.50-
		1.30 (m, 2H), 0.60-0.52 (m, 4H). MS (ESI, m/e)
		[M + 1]+ 568.6.
	211	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.05
		(s, 1H), 9.03 (d, J = 8.8 Hz, 1H), 7.85 (s, 1H),
		7.47-7.45 (m, 1H), 7.35-7.16 (m, 1H), 7.13 (d,
		J = 8.4 Hz, 1H), 4.85-4.82 (m, 1H), 3.23-2.55
		(m, 7H), 2.48 (s, 3H), 2.47-2.38 (m, 1H), 1.89-
		1.82 (m, 1H), 1.59-1.42 (m, 1H), 0.90-0.69 (m,
		7H), 0.51- 0.11 (m, 8H). MS (ESI, m/e) [M + 1]+
		520.6.
	213	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.15
		(s, 1H), 9.07 (d, J = 8.0 Hz, 1H), 7.60-7.57 (m,
		1H), 7.47 (s, 1H), 7.36-7.32 (m, 1H), 7.19-7.16
		(m, 1H), 4.63-4.56 (m, 1H), 4.48-4.44 (m, 1H),
		4.35-4.28 (m, 1H), 3.50-3.45 (m, 1H), 3.15-3.12
		(m, 1H), 3.04-2.98 (m, 2H), 2.91-2.86 (m, 1H),
		2.83-2.77 (m, 1H), 2.47 (s, 3H), 1.87-1.79 (m,
		2H), 1.74-1.68 (m, 2H), 1.65-1.55 (m, 2H),
		1.23-1.05 (m, 5H). MS (ESI, m/e) [M + 1]+ 535.3
	214	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.21
		(s, 1H), 9.24 (d, J = 8.4 Hz, 1H), 9.06 (d, J = 4.4
		Hz, 1H), 7.58-7.47 (m, 2H), 7.44-7.30 (m, 1H),
		7.21-7.11 (m, 3H), 7.02 (d, J = 7.6 Hz, 1H), 6.78
		(s, 1H), 4.58-4.53 (m, 1H), 3.75-3.62 (m, 2H),
		3.28-3.20 (m, 2H), 3.10-3.00 (m, 2H), 2.87 (s,
		2H), 2.48 (s, 3H), 2.20 (s, 3H), 2.10-1.64 (m,
		7H), 1.50-1.30 (m, 2H), 0.50-0.34 (m, 4H). MS
		(ESI, m/e) [M + 1]+ 676.4.
	215	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.68
		(s, 1H), 10.22 (s, 1H), 9.32 (s, 1H), 8.52 (s, 1H),
		7.58-7.25 (m, 3H), 7.12-7.06 (m, 1H), 6.65 (s,
		1H), 4.57-4.53 (m, 1H), 3.65-3.30 (m, 3H),
		3.28-3.10 (m, 3H), 2.89-2.80 (m, 2H), 2.49-2.45
		(m, 3H), 2.01-1.63 (m, 9H), 1.55-1.23 (m, 3H),
		0.48-0.30 (m, 2H), 0.28-0.21 (m, 2H). MS (ESI,
		m/e) [M + 1]+ 669.4
	216	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.13
		(s, 1H), 9.44 (s, 1H), 9.02 (d, J = 8.6 Hz, 1H)
		7.64-7.52 (m, 2H), 7.50-7.35 (m, 4H), 7.30-7.14
		(m, 1H), 6.85 (s, 1H), 6.61 (s, 1H), 4.87-4.83
		(m, 1H), 3.65-3.40 (m, 2H), 3.28-3.26 (m, 4H),
		3.01-2.94 (m, 2H), 2.79-2.65 (m, 3H), 0.89-0.70
		(m, 3H), 0.45-0.11 (m, 12H). MS (ESI, m/e)
		[M + 1]+ 656.3
	217	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.23-
		10.18 (m, 1H), 8.70-8.63 (m, 1H), 7.57-7.42 (m,
		4H), 7.12-7.01 (s, 5H), 4.57-4.53 (m, 3H), 4.03
		(s, 3H), 3.65-3.30 (m, 1H), 3.28-3.10 (m, 4H),
		2.85-2.80 (m, 6H), 2.35-2.30 (m, 1H), 1.87-1.83
		(m, 1H),1.55-1.23 (m, 1H). MS (ESI, m/e)
		[M + 1]+ 615.3
	218	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 9.45 (s, 1H), 8.42 (d, J = 8.0 Hz, 1H),
		7.57 (s, 1H), 7.48 (s, 1H), 7.36-7.32 (m, 1H),
		7.19-7.15 (m, 1H), 4.82-4.78 (m, 1H), 4.63-4.56
		(m, 1H), 4.37-4.28 (m, 1H), 3.51-3.46 (m, 1H),
		3.16-3.13 (m, 1H), 3.04-2.96 (m, 3H), 2.91-2.86
		(m, 1H), 2.83-2.78 (m, 1H), 2.38 (s, 3H), 0.91-
		0.76 (m, 2H), 0.67-0.63 (m, 1H), 0.47-0.42 (m,
		1H), 0.39-0.33 (m, 1H), 0.31-0.26 (m, 2H),
		0.22-0.17 (m, 2H), 0.12-0.07 (m, 1H). MS (ESI,
		m/e) [M + 1]+ 546.3
	219	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.22
		(s, 1H), 9.22 (dd, J = 20.4 Hz, 5.2 Hz, 1H), 7.58-
		7.53 (m, 2H), 7.47-7.30 (m, 1H), 7.24-7.13 (m,
		1H), 6.88-6.83 (m, 1H), 4.58-4.53 (m, 1H),
		3.75-3.62 (m, 2H), 3.28-3.20 (m, 2H), 3.10-3.00
		(m, 2H), 2.90 (s, 2H), 2.69 (s, 1H), 2.48 (s, 3H),
		2.19 (s, 3H), 2.13-1.64 (m, 7H), 1.52-1.30 (m,
		2H), 0.53-0.37 (m, 4H). MS (ESI, m/e) [M + 1]+
		694.4.
	220	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.21
		(s, 1H), 9.32 (s, 1H), 9.22 (d, J = 8.6 Hz, 1H),
		7.39-7.15 (m, 4H), 7.12-7.06 (m, 1H), 6.65 (s,
		1H),4.57-4.53 (m, 1H), 3.65-3.30 (m, 2H),
		3.28-3.10 (m, 4H),2.85-2.80 (m, 2H), 2.49-2.45
		(m, 3H), 2.16 (s, 3H), 2.01-1.83 (m, 8H),1.55-
		1.23 (m, 2H), 0.48-0.30 (m, 4H). MS (ESI, m/e)
		[M + 1]+ 696.4
	221	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.21
		(s, 1H), 9.32 (s, 1H), 9.22 (d, J = 8.6 Hz, 1H),
		7.39-7.15 (m, 4H), 7.12 (s, 3H), 6.65 (s,
		1H),4.57-4.53 (m, 1H), 3.65-3.30 (m, 2H),
		3.28-3.10 (m, 4H),2.85-2.80 (m, 2H), 2.75 (s,
		3H), 2.49-2.45 (m, 3H), 2.16 (s, 3H), 2.01-1.83
		(m, 6H), 1.55-1.23 (m, 2H), 0.48-0.30 (m, 4H).
		MS (ESI, m/e) [M + 1]+ 676.4
	222	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.03
		(d, J = 4.6 Hz, 1H), 9.01 (dd, J = 8.8, 5.4 Hz,
		1H), 8.40 (d, J = 6.8 Hz, 1H), 7.70 (s, 1H), 7.49-
		7.36 (m, 2H), 7.33-7.21 (m, 1H), 7.13-7.08 (m,
		2H), 6.77 (t, J = 6.6 Hz, 1H), 6.12 (s, 1H), 4.82
		(t, J = 7.6 Hz, 1H), 3.92 (t, J = 14.8 Hz, 2H),
		3.43-3.39 (m, 4H), 2.85 (s, 2H), 2.46 (s, 3H),
		0.86-0.68 (m, 3H), 0.57-0.42 (m, 5H), 0.40-0.09
		(m, 7H). MS (ESI, m/e) [M + 1]+ 635.2.
	223	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.13
		(s, 1H), 9.19 (d, J = 8.4 Hz, 1H), 8.40 (d, J = 6.8
		Hz, 1H), 7.70 (s, 1H), 7.59-7.34 (m, 2H), 7.31-
		7.24 (m, 1H), 7.13-7.08 (m, 2H), 6.78 (t, J = 6.8
		Hz, 1H), 6.12 (s, 1H), 4.51 (t, J = 8.4 Hz, 1H),
		3.94 (dd, J = 15.6, 9.8 Hz, 2H), 3.45-3.35 (m,
		4H), 2.86 (s, 2H), 2.45 (s, 3H), 2.02-1.98 (m,
		2H), 1.91-1.59 (m, 5H), 1.47-1.28 (m, 2H), 0.55
		(s, 2H), 0.46 (s, 2H). MS (ESI, m/e) [M + 1]+
		659.5.
	224	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.23-
		10.18 (m, 1H), 8.70-8.63 (m, 1H), 7.57-7.42 (m,
		4H), 7.12-7.01 (s, 4H), 6.75 (s, 1H), 4.57-4.53
		(m, 3H), 4.03 (s, 3H), 3.65-3.30 (m, 1H), 3.28-
		3.10 (m, 4H), 2.85-2.80 (m, 4H), 1.87-1.83 (m,
		1H),1.55-1.23 (m, 1H), 0.89-0.70 (m, 4H). MS
		(ESI, m/e) [M + 1]+ 641.3
	225	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.08
		(s, 1H), 9.01 (d, J = 8.0 Hz, 1H), 7.52-7.29 (m,
		3H), 7.14 (d, J = 8.0 Hz, 1H), 4.90-4.82 (m,
		1H), 4.31 (s, 1H), 3.85 (s, 1H), 3.58 (s, 1H),
		3.43-3.33 (m, 4H), 3.22 (s, 3H), 3.11-3.04 (m,
		2H), 2.53 (s, 3H), 0.85 (s, 2H), 0.78-0.72 (m,
		1H), 0.46 (s, 1H), 0.38 (s, 1H), 0.31 (s, 1H),
		0.25 (s, 2H), 0.16 (s, 1H). MS (ESI) m/e [M + 1]+
		591.4.
	226	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.19
		(s, 1H), 9.07 (d, J = 9.2 Hz, 1H), 7.58-7.53 (m,
		1H), 7.47-7.38 (m, 1H), 7.24 (d, J = 8.4 Hz,
		1H), 6.86 (s, 1H), 4.88-4.83 (m, 1H), 3.75-3.65
		(m, 2H), 3.38-3.25 (m, 2H), 3.15 (s, 2H), 2.93
		(s, 2H), 2.48 (s, 3H), 2.03-1.94 (m, 1H), 0.90-
		0.69 (m, 4H), 0.51-0.11 (m, 10H). MS (ESI,
		m/e) [M + 1]+ 544.6.
	227	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.24
		(s, 1H), 9.38 -9.28 (m, 1H), 7.67-7.57 (m, 1H),
		7.48 (s, 1H), 7.41-7.32 (m, 1H), 7.22-7.17 (m,
		1H), 7.10 -7.03 (m, 1H), 6.73 (s, 1H), 4.72-4.56
		(m, 2H), 4.38-4.28 (m, 1H), 3.55-3.45 (m, 1H),
		3.20-3.13 (m, 2H), 3.08-2.70 (m, 7H), 2.48 (s,
		3H), 2.05-1.80 (m, 2H), 1.48-1.24 (m, 2H),
		0.99-0.65 (m, 4H). MS (ESI, m/e) [M + 1]+
		643.3.
	228	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.21
		(s, 1H), 9.24 (d, J = 8.6 Hz, 1H), 9.09 (d, J = 8.6
		Hz, 1H), 8.24 (s, 1H), 7.57-7.42 (m, 4H), 7.12
		(s, 2H), 6.65 (s, 1H),4.57-4.53 (m, 3H), 3.65-
		3.30 (m, 2H), 3.28-3.10 (m, 5H),2.85-2.80 (m,
		2H), 2.49-2.45 (m, 3H), 2.01-1.83 (m,
		6H),1.55-1.23 (m, 2H), 0.48-0.30 (m, 2H),
		0.17-0.12 (m, 2H). MS (ESI, m/e) [M + 1]+ 678.7
	229	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.21
		(s, 1H), 9.32 (s, 1H), 9.22 (d, J = 8.6 Hz, 1H),
		7.57-7.42 (m, 4H), 7.12 (s, 2H), 6.85 (s, 1H),
		6.65 (s, 1H),4.57-4.53 (m, 1H), 3.65-3.30 (m,
		2H), 3.28-3.10 (m, 4H),2.85-2.80 (m, 2H), 2.75
		(s, 3H), 2.49-2.45 (m, 3H), 2.16 (s, 3H), 2.01-
		1.83 (m, 5H), 1.55-1.23 (m, 2H), 0.48-0.30 (m,
		4H). MS (ESI, m/e) [M + 1]+ 676.3
	230	MS (ESI, m/e) [M + 1]+ 587.4
	231	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 9.03 (d, J = 8.6 Hz, 1H), 7.51 (d, J =
		20.8 Hz, 1H), 7.34 (dd, J = 18.4, 8.8 Hz, 1H),
		7.16 (d, J = 8.2 Hz, 1H), 6.65 (s, 1H), 4.85 (t, J =
		8.0 Hz, 1H), 4.60-4.54 (m, 1H), 3.24-3.22 (m,
		2H), 2.97-2.80 (m, 6H), 2.49-2.47 (m, 3H),
		1.52-1.48 (m, 1H), 0.83-075 (m, 8H), 0.46-0.20
		(m, 8H). MS (ESI, m/e) [M + 1]+ 521.5.
	232	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.18
		(s, 1H), 9.22 (d, J = 8.2 Hz, 1H), 8.21 (s, 1H),
		7.49-7.20 (m, 4H), 7.10-7.01 (m, 3H), 6.64 (s,
		1H), 4.53 (t, J = 8.0 Hz, 1H), 3.47-3.40 (m, 2H),
		3.08-2.96 (m, 4H), 2.87 (d, J = 10.6 Hz, 2H),
		2.82-2.78 (m, 1H), 2.47 (s, 3H), 2.08-1.98 (m,
		2H), 1.90-1.64 (m, 4H), 1.46-1.29 (m, 2H), 1.18
		(s, 2H), 1.03-0.99 (m, 2H), 0.39 (s, 2H), 0.17-
		0.13 (m, 2H). MS (ESI, m/e) [M + 1]+ 720.6.
	233	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.18 (s,
		1H), 9.22 (d, J = 8.4 Hz, 1H), 8.23 (s, 1H), 7.52-
		7.25 (m, 3H), 7.15-7.01 (m, 3H), 6.65 (s, 1H),
		4.54 (t, J = 8.2 Hz, 1H), 3.51-3.47 (m, 2H),
		3.08-2.95 (m, 4H), 2.89 (d, J = 13.4 Hz, 2H),
		2.82 (d, J = 10.2 Hz, 1H), 2.47 (s, 3H), 2.05-
		2.02 (m, 2H), 1.76-1.65 (m, 4H), 1.43-1.35 (m,
		2H), 1.29 (s, 2H), 1.04 (s, 2H), 0.39 (s, 2H),
		0.15-0.12 (m, 2H). MS (ESI, m/e) [M + 1]+
		738.6.
	234	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 9.48 (s, 1H), 9.04 (d, J = 8.8 Hz, 1H),
		7.62-7.46 (m, 3H), 7.44-7.26 (m, 3H), 7.20-7.15
		(m, 1H), 7.03 (t, J = 7.2 Hz, 1H), 6.93 (s, 1H),
		4.88-4.83 (m, 1H), 3.79-3.67 (m, 1H), 3.60-3.53
		(m, 1H), 3.45-3.34 (m, 2H), 3.32-3.25 (m, 1H),
		3.18-3.11 (m, 1H), 2.87-2.80 (m, 1H), 2.03-1.94
		(m, 1H), 1.53-1.44 (m, 1H), 0.90-0.69 (m, 8H),
		0.51-0.11 (m, 9H). MS (ESI, m/e) [M + 1]+
		640.7.
	235	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 9.48 (s, 1H), 8.43 (d, J = 8.8 Hz, 1H),
		7.63-7.48 (m, 4H), 7.44-7.28 (m, 3H), 7.18-7.14
		(m, 1H), 7.03 (t, J = 7.2 Hz, 1H), 6.93 (s, 1H),
		5.44-5.38 (m, 1H), 4.88-4.83 (m, 1H), 3.79-3.67
		(m, 1H), 3.60-3.53 (m, 1H), 3.48-3.38 (m, 2H),
		3.32-3.25 (m, 2H), 3.15-3.07 (m, 1H), 2.87-2.83
		(m, 1H), 1.53-1.34 (m, 7H), 0.93-0.69 (m, 9H),
		0.50-0.05 (m, 8H). MS (ESI, m/e) [M + 1]+
		666.8.
	236	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 9.68 (s, 1H), 9.04 (d, J = 8.8 Hz, 1H),
		7.63-7.46 (m, 2H), 7.42-7.28 (m, 3H), 7.20-7.15
		(m, 1H), 6.94 (s, 1H), 6.85 (t, J = 7.6 Hz, 1H),
		4.88-4.83 (m, 1H), 3.79-3.67 (m, 1H), 3.60-3.53
		(m, 1H), 3.45-3.34 (m, 2H), 3.32-3.25 (m, 2H),
		3.15-3.07 (m, 1H), 2.87-2.80 (m, 1H), 2.48 (s,
		3H), 1.53-1.44 (m, 1H), 0.90-0.69 (m, 9H),
		0.51-0.11 (m, 8H). MS (ESI, m/e) [M + 1]+
		658.6.
	237	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.12
		(d, J = 8.8 Hz, 1H), 8.48 (d, J = 7.4 Hz, 1H),
		7.51-7.45 (m, 2H), 7.20 (d, J = 22.6 Hz, 1H),
		7.12-6.98 (m, 3H), 4.94-4.92 (m, 1H), 4.36 (t, J =
		8.2 Hz, 2H), 4.02 (s, 3H), 3.79-3.64 (m, 1H),
		3.58-3.33 (m, 2H), 3.30-3.14 (m, 3H), 2.86-2.79
		(m, 1H), 1.83-1.80 (m, 2H), 1.69-1.67 (m, 2H),
		1.59-1.56 (m, 2H), 1.15-1.14 (m, 4H). MS (ESI,
		m/e) [M + 1]+ 549.4.
	239	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 8.85 (s, 1H), 8.38 (d, J = 12.0 Hz, 1H),
		7.57 (s, 1H), 7.48 (s, 1H), 7.33-7.31 (m, 1H),
		7.19-7.17 (m, 1H), 4.84-4.81 (m, 1H), 4.63-4.56
		(m, 1H), 4.38-4.28 (m, 1H), 3.52-3.47 (m, 1H),
		3.17-3.13 (m, 1H), 3.04-2.98 (m, 2H), 2.92-2.78
		(m, 2H), 2.11 (s, 3H), 0.95-0.71 (m, 3H), 0.46-
		0.13 (m, 8H). MS (ESI, m/e) [M + 1]+ 546.3
	240	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.26 (s,
		1H), 9.10 (d, J = 8.4 Hz, 1H), 7.96 (s, 1H), 7.66
		(s, 1H), 7.49 (d, J = 8.8 Hz, 1H), 7.39 (d, J = 8.8
		Hz, 1H), 6.77 (s, 1H), 4.49 (t, J = 8.4 Hz, 1H),
		3.65 (t, J = 9.8 Hz, 1H), 3.44-3.31 (m, 1H), 3.33
		(s, 3H), 2.47 (s, 3H), 1.93-1.57 (m, 6H), 123-
		1.04 (m, 5H). MS (ESI, m/e) [M + 1]+547.5
	241	MS (ESI, m/e) [M + 1]+629.6
	242	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.23
		(s, 1H), 9.47 (s, 1H), 9.24 (d, J = 5.2 Hz, 1H),
		7.63 -7.47 (m, 3H), 7.38-7.27 (m, 3H), 7.20-
		7.15 (m, 1H), 7.03 (t, J = 7.2 Hz, 1H), 6.95 (s,
		1H), 6.85 (t, J = 8.0 Hz, 1H), 4.58-4.53 (m, 1H),
		3.72 (t, J = 15.6 Hz, 1H), 3.59-3.42 (m, 3H),
		3.32-3.28 (m, 1H), 3.18-3.10 (m, 1H), 2.93-2.83
		(m, 1H), 2.48 (s, 3H), 2.13-1.65 (m, 7H), 1.54-
		1.30 (m, 3H), 0.85-0.78 (m, 3H), 0.75 (d, J =
		6.4 Hz, 3H). MS (ESI, m/e) [M + 1]+ 664.7.
	243	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.23
		(s, 1H), 9.67 (s, 1H), 9.24 (d, J = 6.0 Hz, 1H),
		7.63-7.47 (m, 2H), 7.45-7.27 (m, 3H), 7.17(t,
		J = 7.2 Hz, 1H), 6.96 (s, 1H), 6.85 (t, J = 8.0 Hz,
		1H), 4.58-4.53 (m, 1H), 3.79-3.68 (m, 1H),
		3.69-3.53 (m, 1H), 3.47-3.39 (m, 2H), 3.32-3.28
		(m, 1H), 3.15-3.07 (m, 1H), 2.93-2.83 (m, 1H),
		2.48 (s, 3H), 2.13-1.65 (m, 7H), 1.54-1.30 (m,
		3H), 0.85-0.78 (m, 3H), 0.75 (d, J = 6.4 Hz,
		3H). MS (ESI, m/e) [M + 1]+ 682.6.
	244	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 9.01 (d, J = 8.8 Hz, 1H), 7.48 (s, 1H),
		7.31 (d, J = 8.0 Hz, 1H), 7.12 (d, J = 8.0 Hz,
		1H), 6.54 (s, 1H), 4.85 (t, J = 7.8 Hz, 1H), 3.53
		(d, J = 10.6 Hz, 2H), 3.41 (d, J = 9.6 Hz, 1H),
		3.27-3.16 (m, 6H), 3.04 (t, J = 14.8 Hz, 2H),
		2.48 (s, 3H), 1.55-1.41 (m, 1H), 0.85 (s, 1H),
		0.80-0.75 (m, 6H), 0.46 (s, 1H), 0.38 (s, 1H),
		0.25-0.14 (m, 6H). MS (ESI) m/e [M + 1]+ 565.7.
	245	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.06
		(s, 1H), 8.40 (d, J = 8.8 Hz, 1H), 7.52-7.29 (m,
		3H), 7.11 (d, J = 7.8 Hz, 1H), 7.05 (s, 1H), 6.53
		(s, 1H), 4.79 (t, J = 8.0 Hz, 1H), 4.04 (s, 3H),
		3.59-3.49 (m, 2H), 3.45-3.36 (m, 2H), 3.27-3.17
		(m, 6H), 3.07-3.01 (m, 2H), 1.48 (d, J = 6.0 Hz,
		1H), 0.84 (s, 1H), 0.80-0.70 (m, 6H), 0.44 (s,
		1H), 0.35 (d, J = 6.2 Hz, 2H), 0.31-0.25 (m,
		1H), 0.21 (s, 3H), 0.10 (s, 1H). MS (ESI) m/e
		[M + 1]+ 563.5.
	246	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.04
		(s, 1H), 8.98 (d, J = 8.4 Hz, 1H), 8.43 (s, 1H),
		8.12-7.99 (m, 2H), 7.47 (d, J = 24.2 Hz, 1H),
		7.32-7.27 (m, 1H), 7.15 (d, J = 5.8 Hz, 2H), 6.61
		(s, 1H), 4.83 (s, 1H), 3.90-3.72 (m, 2H), 3.57-
		3.54 (m, 3H), 3.30-3.15 (m, 2H), 2.47 (s, 3H),
		1.48-1.39 (m, 1H), 0.84 (d, J = 6.6 Hz, 1H),
		0.76-0.72 (m, 6H), 0.44 (s, 1H), 0.37 (s, 1H),
		0.31 (s, 1H), 0.23-0.18 (m, 5H). MS (ESI) m/e
		[M + 1]+ 638.5.
	247	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.17
		(s, 1H), 9.22 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 5.8
		Hz, 1H), 7.32 (t, J = 7.2 Hz, 1H), 7.08 (d, J =
		8.2 Hz, 1H), 6.83 (s, 1H), 6.61 (s, 1H), 4.54 (t,
		J = 8.4 Hz, 1H), 3.31-3.22 (m, 4H), 2.88 (s, 2H),
		2.52 (d, J = 15.8 Hz, 2H), 2.47 (s, 3H), 2.07-
		2.01 (m, 3H), 1.95-1.61 (m, 4H), 1.54-1.26 (m,
		2H), 0.91 (s, 6H), 0.52 (s, 4H). MS (ESI, m/e)
		[M + 1]+ 601.3.
	248	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 9.01 (d, J = 8.8 Hz, 1H), 7.57-7.44 (m,
		2H), 7.38-7.32 (m, 1H), 7.14 (d, J = 7.6 Hz,
		1H), 6.75 (s, 1H), 4.88-4.83 (m, 1H), 3.59-3.36
		(m, 4H), 3.32-3.18 (m, 2H), 2.85-2.80 (m, 1H),
		2.56-2.53 (m, 3H), 2.53 (s, 3H), 1.49-1.40 (m,
		1H), 0.90-0.65 (m, 8H), 0.51-0.09 (m, 8H). MS
		(ESI, m/e) [M + 1]+ 578.8.
	249	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.22
		(s, 1H), 9.33-9.18 (m, 2H), 7.85 (s, 1H), 7.61-
		7.31 (m, 2H), 7.28-7.06 (m, 5H), 4.55 (t, J =
		8.4Hz, 1H), 3.70-3.36 (m, 3H), 3.31-3.19 (m,
		1H), 3.04-2.94 (m, 1H), 2.69 (s, 1H), 2.47 (s,
		3H), 2.10-1.96 (m, 3H), 1.88-1.70 (m, 2H),
		1.55-1.42 (m, 3H), 1.36-1.16 (m, 2H), 0.82-0.73
		(m, 6H). MS (ESI, m/e) [M + 1]+ 682.8.
	250	Isomer A: 1H NMR (400 MHz, DMSO-d6) δ
		ppm: 10.13 (s, 1H), 9.05 (d, J = 8.8 Hz, 1H),
		7.52 (s, 1H), 7.40 (d, J = 8.2 Hz, 1H), 7.18 (d, J =
		8.2 Hz, 1H), 7.14 (s, 1H), 4.87 (t, J = 8.2 Hz,
		1H), 3.61-3.55 (m, 2H), 3.43-3.17 (m, 5H), 2.91
		(s, 1H), 2.49 (s, 3H), 1.35 (s, 3H), 1.15-1.08 (m,
		1H), 0.95-0.74 (m, 2H), 0.73-0.67 (m, 1H),
		0.51-0.33 (m, 8H), 0.33-0.04 (m, 6H). MS (ESI,
		m/e) [M + 1]+ 633.4. Retention time(Prep-HPLC):
		8.0 min.
		Isomer B: 1H NMR (400 MHz, DMSO-d6) δ
		ppm: 10.14 (d, J = 5.2 Hz, 1H), 9.06 (d, J = 8.8
		Hz, 1H), 7.64-7.33 (m, 2H), 7.28-7.20 (m, 1H),
		7.17-7.18 (m, 1H), 4.87 (s, 1H), 3.63-3.56 (m,
		2H), 3.39-3.21 (m, 5H), 3.09-2.96 (m, 1H), 2.50
		(s, 3H), 1.24-1.11 (m, 4H), 0.99-0.65 (m, 6H),
		0.55-0.10 (m, 11H). MS (ESI, m/e) [M + 1]+
		633.3. Retention time(Prep-HPLC): 8.8 min.
		Isomer C: 1H NMR (400 MHz, DMSO-d6) δ
		ppm: 10.13 (s, 1H), 9.04 (d, J = 8.8 Hz, 1H),
		7.56 (s, 1H), 7.35 (d, J = 8.2 Hz, 1H), 7.18 (d,
		J = 8.2 Hz, 1H), 7.08 (s, 1H), 4.85 (t, J = 7.8 Hz,
		1H), 3.59-3.52 (m, 1H), 3.41-3.36 (m, 2H),
		3.23-3.00 (m, 5H), 2.49 (s, 3H), 1.41-1.36 (m,
		4H), 0.97-0.66 (m, 8H), 0.51-0.12 (m, 9H). MS
		(ESI, m/e) [M + 1]+ 633.4. Retention time(Prep-
		HPLC): 9.4 min.
	251	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 9.03 (d, J = 8.0 Hz, 1H), 7.57-7.29 (m,
		4H), 7.19-7.15 (m, 1H), 7.11-7.07 (m, 1H), 6.61
		(s, 1H), 4.87-4.83 (m, 1H), 3.85-3.64 (m, 2H),
		3.36-3.37 (m, 3H), 3.23-3.16 (m, 1H), 2.97-2.91
		(m, 1H), 2.48 (s, 3H), 0.89-0.67 (m, 10H), 0.49-
		0.14 (m, 8H). MS (ESI, m/e) [M + 1]+ 615.6
	252	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.05
		(s, 1H), 9.08-9.00 (m, 1H), 7.78 (s, 1H), 7.57-
		7.48 (m, 2H), 7.43-7.30 (m, 2H), 7.23-6.93 (m,
		1H), 4.88-4.83 (m, 1H), 3.79-3.36 (m, 6H),
		3.32-3.18 (m, 1H), 2.48 (s, 3H), 2.05-1.88 (m,
		2H), 1.52-1.45 (m, 2H), 0.96-0.70 (m, 10H),
		0.51-0.06 (m, 8H). MS (ESI, m/e) [M + 1]+
		627.8.
	253	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.23
		(s, 1H), 9.25 (d, J = 8.6 Hz, 1H), 9.03 (d, J = 8.6
		Hz, 1H), 7.54-7.42 (m, 3H), 7.20-7.01 (m, 5H),
		4.57-4.53 (m, 4H), 3.65-3.30 (m, 1H), 3.28-3.26
		(m, 1H), 2.75 (s, 3H), 2.49-2.45 (m, 3H), 2.16
		(s, 3H), 2.01-1.83 (m, 5H), 1.55-1.23 (m, 5H),
		0.79-0.50 (m,6H). MS (ESI, m/e) [M + 1]+ 678.5
	254	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.13 (s,
		1H), 9.04 (d, J = 8.8Hz, 1H), 8.88 (s, 1H), 8.15
		(d, J = 7.6 Hz, 1H), 7.56-7.33 (m, 2H), 7.24-
		7.12 (m, 2H), 7.02 (d, J = 4.0 Hz, 2H), 6.89 (s,
		1H), 4.88-4.84 (m, 1H), 3.79(s, 3H), 3.72-3.47
		(m, 2H), 3.42-3.36 (m, 2H), 3.38-3.15 (m, 2H),
		3.15-3.10 (m, 1H), 2.48 (s, 3H), 1.60-1.51 (m,
		1H), 0.91-0.70 (m, 7H), 0.52-0.11 (m, 10H).
		MS (ESI, m/e) [M + 1]+ 670.8
	255	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(d, J = 5.0 Hz, 1H), 9.05 (d, J = 8.8 Hz, 1H),
		7.52 (d, J = 5.8 Hz, 1H), 7.18-7.08 (m, 2H), 6.98
		(d, J = 8.0 Hz, 1H), 4.96-4.92 (m, 1H), 4.84 (t,
		J = 7.8 Hz, 1H), 4.36 (s, 1H), 3.79-3.66 (m, 1H),
		3.59-3.38 (m, 2H), 3.30-3.14 (m, 2H), 2.87-2.82
		(m, 1H), 2.48 (s, 3H), 0.90-0.66 (m, 3H), 0.47-
		0.11 (m, 8H). MS (ESI, m/e) [M + 1]+ 563.5.
	257	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.21
		(d, J = 7.8 Hz, 1H), 9.23 (d, J = 8.5 Hz, 1H),
		7.52 (d, J = 5.8 Hz, 1H), 7.22-7.08 (m, 2H),
		7.01-6.96 (m, 1H), 4.95-4.94 (m, 1H), 4.52 (t,
		J = 8.2 Hz, 1H), 4.36 (s, 1H), 3.79-3.67 (m, 1H),
		3.57-3.41 (m, 2H), 3.28-3.16 (m, 2H), 2.86-2.82
		(m, 1H), 2.47 (s, 3H), 2.04-2.00 (m, 3H), 1.86-
		1.65 (m, 4H), 1.47-1.30 (m, 2H). MS (ESI, m/e)
		[M + 1]+ 587.6.
	258	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.18
		(d, J = 7.5 Hz, 1H), 8.62 (d, J = 7.5 Hz, 1H),
		7.54-7.44 (m, 2H), 7.23-6.99 (m, 4H), 4.95-4.93
		(m, 1H), 4.48-4.37 (m, 2H), 4.03 (s, 3H), 3.79-
		3.67 (m, 1H), 3.57-3.41 (m, 2H), 3.29-3.15 (m,
		2H), 2.84 (d, J = 17.2 Hz, 1H), 2.05-2.01 (m,
		3H), 1.88-1.63 (m, 4H), 1.43-1.29 (m, 2H). MS
		(ESI, m/e) [M + 1]+ 585.6.
	259	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 9.65 (s, 1H), 9.08-9.00 (m, 1H), 7.78 (s,
		1H), 7.57-7.48 (m, 2H), 7.43-7.30 (m, 2H),
		7.23-7.09 (m, 2H), 6.93 (s, 1H), 4.88-4.83 (m,
		1H), 3.79-3.36 (m, 4H), 3.32-3.18 (m, 2H),
		2.85-2.80 (m, 1H), 2.48 (s, 3H), 1.52-1.45 (m,
		1H), 0.96-0.70 (m, 9H), 0.51-0.09 (m, 8H). MS
		(ESI, m/e) [M + 1]+ 674.3.
	260	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.13
		(s, 1H), 10.01 (s, 1H), 9.08-9.04 (m, 1H), 8.06
		(s, 1H), 7.77-7.75 (m, 2H), 7.53-7.30 (m, 2H),
		7.25-7.20 (m, 1H), 6.99 (s, 1H), 4.88-4.83 (m,
		1H), 3.79-3.36 (m, 4H), 3.32-3.18 (m, 1H),
		2.85-2.80 (m, 1H), 2.48 (s, 3H), 0.96-0.70 (m,
		10H), 0.51-0.09 (m, 8H). MS (ESI, m/e)
		[M + 1]+ 742.3.
	262	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.13
		(s, 1H), 9.29 (d, J = 8.6 Hz, 1H),9.02 (d, J = 8.6
		Hz, 1H) 7.84-7.80 (m, 1H), 7.50-7.35 (m, 4H),
		7.30-7.14 (m, 3H), 4.87-4.83 (m, 1H), 3.65-3.30
		(m, 4H), 3.28-3.26 (m, 2H), 3.01-2.94 (m, 1H),
		2.49-2.45 (m, 3H), 1.55-1.53 (m, 1H), 0.79-0.70
		(m,9H), 0.45-0.11 (m, 8H). MS (ESI, m/e)
		[M + 1]+ 658.3
	263	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.13
		(s, 1H), 9.17 (d, J = 8.6 Hz, 1H),9.06 (d, J = 8.6
		Hz, 1H) 7.96-7.94 (m, 2H), 7.50-7.35 (m, 4H),
		7.30-7.14 (m, 3H), 4.89-4.87 (m, 1H), 3.65-3.30
		(m, 4H), 3.28-3.26 (m, 2H), 3.01-2.94 (m, 1H),
		2.49-2.45 (m, 3H), 1.55-1.53 (m, 1H), 0.79-0.70
		(m,9H), 0.29-0.11 (m, 7H). MS (ESI, m/e)
		[M + 1]+ 674.3
	264	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.12
		(s, 1H), 9.23 (d, J = 6.0 Hz, 1H), 9.03 (d, J = 8.8
		Hz, 1H), 7.96-7.88 (dd, J = 5.2, 8.8 Hz, 1H),
		7.66 (d, J = 2.0 Hz, 1H), 7.56-7.46 (m, 1H),
		7.45-7.33 (m, 2H), 7.23-7.11 (m, 2H), 4.85 (t, J =
		7.6 Hz, 1H), 3.71-3.61 (m, 1H), 3.59-3.48 (m,
		2H), 3.44-3.33 (m, 2H), 3.27-3.20 (m, 1H),
		3.01-2.93 (m, 1H), 2.48 (s, 3H), 1.56-1.47 (m,
		1H), 0.91-0.84 (m, 1H), 0.81-0.72 (m, 8H),
		0.49-0.35 (m, 2H), 0.33-0.13 (m, 6H). MS (ESI,
		m/e) [M + 1]+ 708.6.
	265	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 9.80 (s, 1H), 9.02 (dd, J = 3.6, 8.4 Hz,
		1H), 7.75 (s, 2H), 7.56-7.46 (m, 1H), 7.44-7.31
		(m, 1H), 7.25 (s, 1H), 7.19-7.15 (m, 1H), 6.96
		(s, 1H), 4.92-4.80 (m, 1H), 3.77-3.72 (m, 1H),
		3.61-3.51 (m, 1H), 3.47-3.33 (m, 2H), 3.28 (s,
		1H), 3.07-3.02 (m, 1H), 2.85-2.78 (m, 1H), 2.49
		(s, 3H), 1.48-1.45 (m, 1H), 0.88-0.84 (m, 1H),
		0.82-0.69 (m, 8H), 0.51-0.36 (m, 2H), 0.33-0.12
		(m, 6H). MS (ESI, m/e) [M + 1]+ 708.2.
	266	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07-
		9.93 (m, 1H), 8.54-8.45 (m, 1H), 8.23-8.11 (m,
		1H), 8.08-7.92 (m, 1H), 7.87-7.69 (m, 1H),
		6.91-6.80 (m, 1H), 5.56-5.42 (m, 1H), 4.34-3.92
		(m, 6H), 3.79-3.68 (m, 1H), 3.09-3.03 (m, 3H),
		2.26-2.14 (m, 1H), 1.82-1.76 (m, 1H), 1.49-1.42
		(m, 6H), 1.07-0.69 (m, 10H). MS (ESI, m/e)
		[M + 1]+ 546.5.
	267	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 9.11-8.99 (m, 2H), 7.79-7.71 (m, 1H),
		7.54-7.33 (m, 2H), 7.21-7.16 (m, 2H), 7.13-7.10
		(m, 1H), 7.02 (d, J = 8.4 Hz, 1H), 4.85 (t, J =
		8.0 Hz,1H), 3.76-3.44 (m, 4H), 3.42-3.40 (m,
		1H), 3.27-3.21 (m, 1H), 3.02-2.91 (m, 1H),
		2.50-2.48 (m, 3H), 1.96-1.86 (m, 1H), 1.57-1.46
		(m, 1H), 0.94-0.92 (m, 2H), 0.89-0.84 (m, 1H),
		0.82-0.71 (m, 8H), 0.67-0.64 (m, 2H), 0.49-0.36
		(m, 2H), 0.33-0.13 (m, 6H). MS (ESI, m/e)
		[M + 1]+ 714.3.
	268	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.12
		(s, 1H), 9.58 (d, J = 8.4 Hz, 1H), 9.05 (d, J = 8.8
		Hz, 1H), 7.59 (d, J = 7.6 Hz, 1H), 7.57-7.42 (m,
		2H), 7.42-7.31 (m, 3H), 7.23-7.15 (m, 1H),
		7.11-7.05 (m, 1H), 4.85 (t, J = 8.0 Hz, 1H),
		3.62-3.52 (m, 1H), 3.79-3.51 (m, 1H), 3.44 (d,
		J = 6.0 Hz, 1H), 3.39 (s, 1H), 3.33-3.22 (m, 4H),
		3.09 (d, J = 16.8 Hz, 1H), 2.89-2.80 (m, 1H),
		2.48 (s, 3H), 1.51-1.42 (m, 1H), 0.91-0.79 (m,
		1H), 0.78-0.67 (m, 8H), 0.50-0.28 (m, 2H),
		0.28-0.10 (m, 4H). MS (ESI, m/e) [M + 1]+
		690.3.
	269	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 9.62 (s, 1H), 9.08-8.99 (m, 1H), 7.64 (d,
		J = 1.8 Hz, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7.55-
		7.45 (m, 1H), 7.37-7.32 (m, 3H), 7.17 (dd, J =
		4.8, 8.0 Hz, 1H), 6.93 (s, 1H), 4.89-4.81 (m,
		1H), 3.79-3.67 (m, 1H), 3.60-3.51 (m, 1H), 3.43
		(s, 1H), 3.39-3.37 (m, 1H), 3.31-3.27 (m, 1H),
		3.10 (d, J = 16.8 Hz, 1H), 2.84 (q, J = 8.0 Hz,
		1H), 2.48 (s, 3H), 2.07 (s, 1H), 1.51-1.41 (m,
		1H), 0.91-0.82 (m, 1H), 0.78-0.75 (m, 4H),
		0.72-0.69 (m, 4H), 0.50-0.42 (m, 1H), 0.41-0.35
		(m, 1H), 0.34-0.17 (m, 6H), 0.17-0.11 (m, 1H).
		MS (ESI, m/e) [M + 1]+ 674.3.
	270	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 9.02 (d, J = 8.8 Hz, 1H), 7.67-7.30 (m,
		3H), 7.18 (dd, J = 18.6, 8.4 Hz, 1H), 7.09-6.92
		(m, 1H), 4.93-4.84 (m, 2H), 4.27 (s, 1H), 3.71-
		3.63 (m, 1H), 3.52-3.40 (m, 2H), 3.33-3.05 (m,
		3H), 2.49 (s, 3H), 0.96-0.66 (m, 3H), 0.47-0.13
		(m, 8H). MS (ESI, m/e) [M + 1]+ 645.4.
	271	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 9.04 (d, J = 8.6 Hz, 1H), 7.19-7.04 (m,
		2H), 6.99-6.9 (m, 1H), 6.68 (s, 1H), 4.89-4.87
		(m, 2H), 3.50-3.02 (m, 8H), 2.89-2.80 (m, 1H),
		2.49-2.45 (m, 2H), 1.55-1.33 (m, 1H), 0.79-0.70
		(m,10H), 0.29-0.11 (m, 9H). MS (ESI, m/e)
		[M + 1]+ 537.5
	272	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 9.21-9.16 (m, 1H), 9.01 (d, J = 8.8 Hz,
		1H), 7.80-7.73 (m, 1H), 7.73-7.64 (m, 2H),
		7.56-7.47 (m, 1H), 7.42-7.33 (m, 2H), 7.20-7.11
		(m, 2H), 4.89-4.83 (m, 1H), 3.72-3.61 (m, 1H),
		3.57-3.48 (m, 2H), 3.46-3.39 (m, 1H), 3.35 (d,
		J = 6.8 Hz, 1H), 3.20 (dd, J = 2.8, 16.8 Hz, 1H),
		2.97-2.88 (m, 1H), 2.48 (s, 3H), 1.54-1.47 (m,
		1H), 0.91-0.84 (m, 1H), 0.83-0.69 (m, 8H),
		0.50-0.13 (m, 8H). MS (ESI, m/e) [M + 1]+
		708.3.
	273	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.08
		(s, 1H), 9.00 (d, J = 8.8 Hz, 1H), 8.02-7.91 (dd,
		J = 3.2, 29.6 Hz, 1H), 7.47 (d, J = 8.0 Hz, 1H),
		7.41-7.31 (m, 1H), 7.14 (d, J = 8.4 Hz, 1H), 6.85
		(s, 1H), 4.89-4.82 (dd, J = 2.0, 7.2 Hz, 1H),
		3.65-3.36 (m, 3H), 3.27-3.17 (m, 3H), 2.94-2.74
		(m, 1H), 2.48 (s, 3H), 1.91-1.79 (m, 1H), 1.57-
		1.38 (m, 2H), 0.87-0.66 (m, 10H), 0.49-0.36 (m,
		2H), 0.31-0.12 (m, 6H). MS (ESI, m/e) [M + 1]+
		640.3.
	274	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.09
		(s, 1H), 9.46-9.36 (m, 1H), 9.01 (d, J = 8.8 Hz,
		1H), 8.85 (d, J = 4.0 Hz, 1H), 8.32 (d, J = 5.6
		Hz, 1H), 7.60 (d, J = 5.2 Hz, 1H), 7.56-7.47 (m,
		1H), 7.44-7.33 (m, 1H), 7.19 (d, J = 7.2 Hz,
		1H), 7.11 (s, 1H), 4.86 (dd, J = 7.2, 8.8 Hz, 1H),
		3.76-3.64 (m, 1H), 3.61-3.48 (m, 2H), 3.47-3.40
		(m, 1H), 3.21 (dd, J = 3.6, 16.8 Hz, 2H), 2.99-
		2.91 (m, 1H), 2.48 (s, 3H), 1.55-1.46 (m, 1H),
		0.92-0.84 (m, 1H), 0.81-0.72 (m, 8H), 0.50-0.43
		(m, 1H), 0.41-0.38 (m, 1H), 0.34-0.30 (m, 1H),
		0.29-0.12 (m, 5H). MS (ESI, m/e) [M + 1]+
		675.3.
	275	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 9.40 (d, J = 8.4 Hz, 1H), 9.01 (d, J = 8.4
		Hz, 1H), 7.55-7.46 (m, 1H), 7.40-7.31 (m, 2H),
		7.32-7.31 (m, 1H), 7.28-7.22 (m, 1H), 7.20-7.15
		(m, 1H), 6.97 (s, 1H), 4.86 (t, J = 7.6 Hz, 1H),
		3.70-3.49 (m, 4H), 3.30-3.26 (m, 1H), 3.01-2.89
		(m, 1H), 2.49-2.48 (m, 3H), 1.55-1.42 (m, 1H),
		0.91-0.84 (m, 1H), 0.80-0.76 (m, 4H), 0.75-0.70
		(m, 4H), 0.32 (br s, 3H), 0.30-0.13 (m, 6H). MS
		(ESI, m/e) [M + 1]+ 692.2
	276	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.12-
		10.10 (m, 1H), 9.05 (m, 1H), 7.49-7.45 (m, 1H),
		7.22 (s, 1H), 7.16-7.04 (m, 1H), 6.95 (d, J = 8.0
		Hz, 1H), 4.95-4.84 (m, 2H), 4.42 (s, 1H), 3.99-
		3.67 (m, 2H), 3.52-3.41 (m, 1H), 3.25-3.09 (m,
		1H), 2.94-2.80 (m, 1H), 2.48 (s, 2H), 1.26-1.09
		(m, 4H), 0.79-0.70 (m, 3H), 0.43-0.11(m, 8H).
		MS (ESI, m/e) [M + 1]+ 577.4.
	277	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.12-
		10.10 (m, 1H), 8.43 (d, J = 8.8 Hz, 1H), 7.52-
		7.45 (m, 2H), 7.27-6.88 (m, 4H), 5.46-5.33 (m,
		1H), 4.85-4.80 (m, 2H), 4.44-4.40 (m, 1H),
		3.85-3.70 (m, 2H), 3.55-3.50 (m, 1H), 3.27-3.10
		(m, 1H), 2.92-2.87 (m, 1H), 1.36 (dd, J = 13.8,
		6.6 Hz, 6H), 1.25-1.19 (m, 1H), 1.15-1.09 (m,
		2H), 0.88-0.68 (m, 3H), 0.49-0.03 (m, 8H). MS
		(ESI, m/e) [M + 1]+ 603.4.
	278	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.11
		(s, 1H), 9.22 (d, J = 6.4 Hz, 1H), 9.01 (d, J = 9.2
		Hz, 1H), 7.95-7.86 (m, 1H), 7.58-7.47 (m, 2H),
		7.44-7.34 (m, 1H), 7.22-7.16 (m, 2H), 7.05-6.98
		(m, 1H), 4.85 (dd, J = 7.2, 8.4 Hz, 1H), 3.70-
		3.55 (m, 2H), 3.54-3.49 (m, 1H), 3.42-3.36 (m,
		1H), 3.29-3.23 (m, 1H), 3.01-2.98 (m, 1H), 2.48
		(s, 3H), 1.54-1.51 (m, 1H), 0.91-0.85 (m, 1H),
		0.82-0.72 (m, 8H), 0.50-0.10 (m, 9H). MS (ESI,
		m/e) [M + 1]+ 692.3.
	280	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 9.00 (d, J = 8.8 Hz, 1H), 7.61 (s, 1H),
		7.46 (d, J = 16.8 Hz, 1H), 7.35 (dd, J = 7.6, 18.4
		Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H), 6.85 (s, 1H),
		4.93-4.78 (t, J = 7.6 Hz, 1H), 4.26-4.22 (m, 1H),
		3.79-3.69 (m, 2H), 3.68-3.52 (m, 2H), 3.49-3.40
		(m, 2H), 3.36 (s, 1H), 3.31-3.20 (m, 2H), 3.15-
		3.04 (m, 1H), 2.86-2.80 (m, 1H), 2.48 (s, 3H),
		2.10-1.97 (m, 1H), 1.80-1.70 (m, 1H), 1.48-1.37
		(m, 1H), 0.91-0.83 (m, 1H), 0.81-0.65 (m, 8H),
		0.50-0.35 (m, 2H), 0.34-0.12 (m, 6H). MS (ESI,
		m/e) [M + 1]+ 634.2.
	281	1H NMR (400 MHz, DMSO-d6) δ ppm: 8.81 (s,
		1H), 8.47 (s, 1H), 7.87-7.81 (m, 1H), 7.69 (d,
		J = 8.0 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.27-
		7.11 (m, 2H), 6.76-6.66 (m, 1H), 5.76-5.56 (m,
		1H), 5.35-5.26 (m, 1H), 5.08-4.83 (m, 1H),
		3.99-3.96 (m, 1H), 3.45-3.41 (m, 1H), 3.38-3.33
		(m, 2H), 3.32-3.18 (m, 4H), 2.48 (s, 3H), 1.75-
		1.52 (m, 3H), 1.01-0.29 (m, 22H).
	282	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.07
		(s, 1H), 9.01 (d, J = 8.8 Hz, 1H), 7.47 (d, J =
		14.8 Hz, 1H), 7.37-7.30 (m, 2H), 7.14 (d, J =
		8.0 Hz, 1H), 6.88 (s, 1H), 4.88-4.83 (m, 1H),
		3.99-3.96 (m, 1H), 3.45-3.41 (m, 1H), 3.38-3.33
		(m, 4H), 3.32-3.18 (m, 3H), 2.96-2.93 (m, 1H),
		2.48 (s, 3H), 1.81-1.70 (m, 2H), 1.69-1.65 (m,
		2H), 1.55-1.35 (m, 5H), 0.95-0.70 (m, 7H),
		0.51-0.19 (m, 8H). MS (ESI, m/e) [M + 1]+
		632.6.
	283	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.14-
		10.09 (m, 1H), 9.70 (d, J = 3.6 Hz, 1H), 9.02 (d,
		J = 9.2 Hz, 1H), 7.83-7.79 (m, 1H), 7.67 (d, J =
		2.0 Hz, 1H), 7.56-7.48 (m, 1H), 7.44-7.31 (m,
		2H), 7.19 (d, J = 8.0 Hz, 1H), 7.07 (d, J = 2.0
		Hz, 1H), 4.91-4.81 (m, 1H), 3.74 (t, J = 17.6 Hz,
		1H), 3.61-3.54 (m, 1H), 3.53-3.39 (m, 2H),
		3.31-3.27 (m, 1H), 3.16 (dd, J = 3.2, 16.8 Hz,
		1H), 2.91-2.82 (m, 1H), 2.49 (br s, 3H), 1.55-
		1.46 (m, 1H), 0.92-0.85 (m, 1H), 0.81-0.70 (m,
		8H), 0.51-0.44 (m, 1H), 0.42-0.36 (m, 1H),
		0.35-0.30 (m, 1H), 0.29-0.13 (m, 5H). MS (ESI,
		m/e) [M + 1]+ 665.3.
	284	1H NMR (400 MHz, CDCl3) δ ppm: 8.32-8.31
		(m, 1H), 8.42-8.26 (m, 1H), 7.89-7.78 (m, 1H),
		7.57-7.45 (m, 1H), 7.34 (s, 1H), 7.25-7.19 (m,
		1H), 5.08-4.83 (m, 1H), 3.92-3.17 (m, 7H),
		2.64-2.52 (m, 3H), 1.77-1.70 (m, 1H), 1.55-1.43
		(m, 1H), 1.36-1.22 (m, 2H), 1.00-0.86 (m, 6H),
		0.83-0.76 (m, 2H), 0.60-0.49 (m, 2H), 0.45-0.30
		(m, 2H), 0.28-0.14 (m, 2H). MS (ESI, m/e)
		[M + 1]+ 675.3.
	285	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.10
		(s, 1H), 9.11-8.88 (m, 1H), 8.53 (s, 1H), 7.67 (s,
		1H), 7.57-7.45 (m, 1H), 7.45-7.24 (m, 2H),
		7.18-7.14 (m, 1H), 6.95-6.91 (m, 1H), 3.48-3.39
		(m, 1H), 3.30-3.23 (m, 2H), 3.17-3.05 (m, 1H),
		2.85-2.80 (m, 1H), 2.45-2.40 (m, 3H), 1.50-1.42
		(m, 1H), 0.90-0.83 (m, 1H), 0.83-0.73 (m, 5H),
		0.71-0.69 (m, 3H), 0.50-0.43 (m, 1H), 0.41-0.35
		(m, 1H), 0.34-0.11 (m, 6H). MS (ESI, m/e)
		[M + 1]+ 647.3.
	286	1H NMR (400 MHz, DMSO-d6) δ ppm: 9.83 (s,
		1H), 8.37 (d, J = 9.2 Hz, 1H), 7.49 (s, 1H), 6.95-
		6.81 (m, 3H), 6.69 (d, J = 7.8 Hz, 1H), 6.62 (s,
		1H), 5.73 (s, 1H), 5.40 (s, 1H), 4.76 (t, J = 9.4
		Hz, 1H), 3.25-2.87 (m, 8H), 1.55-1.43 (m, 1H),
		1.51-1.42 (m, 6H), 0.91-0.72 (m, 10H), 0.44-
		0.10 (m, 8H). MS (ESI, m/e) [M + 1]+ 562.5.
	287	1H NMR (400 MHz, DMSO-d6) δ ppm: 9.89 (d,
		J = 7.2 Hz, 1H), 8.33 (d, J = 8.8 Hz, 1 H), 7.50
		(s, 1 H), 6.95-6.74 (m, 4 H), 6.64 (d, J = 9.4 Hz,
		1 H), 5.41 (s, 1 H), 4.77 (t, J = 8.4 Hz, 1 H),
		3.55-3.37 (m, 3 H), 3.28-2.90 (m, 4 H), 2.69 (d,
		J = 4.4 Hz, 3 H),2.66-2.62 (m, 1 H), 1.36 (dd, J =
		11.6, 6.6 Hz, 6H), 0.89-0.65 (m, 10 H), 0.35-
		0.11 (m, 8H). MS (ESI, m/e) [M + 1]+ 576.5.
	288	1H NMR (400 MHz, CDCl3) δ ppm: 8.70-8.57
		(m, 1H), 8.41-8.28 (m, 1H), 7.81-7.75 (m, 1H),
		7.72-7.68 (m, 1H), 7.52-7.45 (m, 1H), 7.39-7.27
		(m, 1H), 7.23-7.18 (m, 2H), 7.04 (br s, 2H),
		7.05-7.03 (m, 1H), 5.63-5.21 (m, 1H), 4.96-4.86
		(m, 1H), 4.11-3.93 (m, 1H), 3.90-3.79 (m, 1H),
		3.59-3.26 (m, 4H), 2.88-2.78 (m, 1H), 2.77-2.67
		(m, 1H), 2.60-2.58 (m, 3H), 1.71-1.65 (m, 1H),
		1.13-1.05 (m, 6H), 0.99-0.75 (m, 12H), 0.62-
		0.50 (m, 2H), 0.35-0.27 (m, 2H). MS (ESI, m/e)
		[M + 1]+ 682.5.
	289	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.08
		(s, 1H), 9.05-8.99 (m, 2H), 7.57-7.47 (m, 1H),
		7.46-7.34 (m, 2H), 7.23-7.17 (m, 2H), 7.16-7.08
		(m, 2H), 7.06-7.02 (m, 1H), 4.86 (dd, J = 7.2,
		8.4 Hz, 1H), 3.70-3.67 (m, 1H), 3.62-3.50 (m,
		2H), 3.46-3.39 (m, 1H), 3.03-2.90 (m, 1H),
		1.54-1.44 (m, 1H), 1.09 (t, J = 7.6 Hz, 3H),
		0.92-0.83 (m, 1H), 0.79-0.72 (m, 8H), 0.51-0.12
		(m, 8H). MS (ESI, m/e) [M + 1]+ 668.7.
	290	Isomer A: 1H NMR (400 MHz, DMSO-d6) δ
		ppm: 10.07 (s, 1H), 8.42 (d, J = 8.8 Hz, 1H),
	291	7.53-7.50 (m, 2H), 7.22-6.89 (m, 4H), 5.43-5.40
		(m, 1H), 4.99-4.97 (m, 1H), 4.77 (s, 1H), 4.39-
		4.37 (m, 1H), 3.87-3.85 (m, 1H), 3.08-3.04(m,
		3H), 1.38-1.33 (m, 6H), 1.12-0.99 (m, 1H),
		0.79-0.70 (m, 4H), 0.52-0.04 (m, 11H). MS
		(ESI, m/e) [M + 1]+ 629.4. Retention time(Prep-
		HPLC): 7.4 min
		Isomer B: 1H NMR (400 MHz, DMSO-d6) δ
		ppm: 10.11 (s, 1H), 8.44 (d, J = 8.8 Hz, 1H),
		7.51-7.40 (m, 2H), 7.27 (s, 1H), 7.17-7.08 (m,
		1H), 7.02-6.88 (m, 2H), 5.48-5.31 (m, 1H),
		4.98-4.95 (m, 1H), 4.78-4.76 (m, 1H), 4.40-4.35
		(m, 1H), 3.85 (s, 1H), 3.63-3.60 (m, 1H), 3.24-
		2.99 (m, 3H), 1.40-1.30 (m, 6H), 1.05 (s, 1H),
		0.91-0.69 (m, 3H), 0.54-0.50 (m, 3H), 0.40-0.15
		(m, 7H). MS (ESI, m/e) [M + 1]+ 629.4.
		Retention time(Prep-HPLC): 8.2 min
		1H NMR (400 MHz, DMSO-d6) δ ppm: 10.15
		(s, 1H), 8.54 (d, J = 8.4 Hz, 1H), 7.58-7.50 (m,
		2H), 7.31-6.98 (m, 4H), 4.47-4.43 (m, 2H),
		4.20-4.05 (m, 4H), 3.80-3.77 (m, 2H), 3.53-3.50
		(m, 1H), 3.24-3.22 (m, 1H), 3.09-3.08 (m, 1H),
		2.76-2.73 (m, 1H), 2.49-2.28 (m, 2H), 1.95-1.65
		(m, 6H), 1.82-1.58 (m, 4H), 1.24-1.20 (m, 3H).
		MS (ESI, m/e) [M + 1]+ 563.4.
	292	Isomer A: 1H NMR (400 MHz, DMSO-d6) δ
		ppm: 10.10 (s, 1H), 9.03 (d, J = 8.6 Hz, 1H),
		7.61-7.28 (m, 2H), 7.17 (d, J = 7.6 Hz, 1H), 6.59
		(s, 1H), 4.85 (t, J = 8.0 Hz, 1H), 4.01 (s, 1H),
		3.51-3.36 (m, 2H), 3.27-3.11 (m, 3H), 3.07-3.00
		(m, 2H), 2.81-2.77 (m, 1H), 2.48 (s, 3H), 1.35-
		1.23 (m, 3H), 0.93-0.58 (m, 10H), 0.48-0.14 (m,
		8H). MS (ESI, m/e) [M + 1]+ 632.4. Retention
		time(Prep-HPLC): 7.9 min.
		Isomer B: 1H NMR (400 MHz, DMSO-d6) δ
		ppm: 10.10 (s, 1H), 9.04 (d, J = 8.8 Hz, 1H),
		7.53 (t, J = 14.6 Hz, 1H), 7.43-7.27 (m, 1H),
		7.20-7.12 (m, 1H), 6.55 (s, 1H), 4.85 (t, J = 7.8
		Hz, 1H), 4.14-4.08 (m, 1H), 3.52-3.45 (m, 3H),
		3.26-3.17 (m, 2H), 3.19-3.03 (m, 2H), 2.84-2.76
		(m, 1H), 2.59 (s, 1H), 2.48 (s, 3H), 1.26-1.18
		(m, 3H), 0.92-0.66 (m, 4H), 0.50-0.45 (m, 6H),
		0.37-0.11 (m, 7H). MS (ESI, m/e) [M + 1]+
		632.4. Retention time(Prep-HPLC): 9.4 min.
	293	1H NMR (400 MHz, DMSO-d6) δ ppm: 10.00
		(d, J = 8.8 Hz, 1H), 9.01-8.96 (m, 1H), 7.52 (s,
		1H), 7.48 (s, 1H), 7.24 (t, J = 8.4 Hz, 1H), 6.70
		(t, J = 8.8 Hz, 1H), 4.98-4.80 (m, 2H), 4.42-4.30
		(m, 1H), 3.79-3.65 (m, 1H), 3.59-3.37 (m, 2H),
		3.32-3.15 (m, 2H), 2.95-2.85 (m, 1H), 2.42 (s,
		3H), 0.90-0.68 (m, 3H), 0.49-0.12 (m, 8H). MS
		(ESI, m/e) [M + 1]+ 563.4.

Biological Assays:

The biological activity of the compounds of the present disclosure was determined utilizing the assays described herein. Values may fluctuate depending on the daily assay performance, fluctuations of this kind a known to those skilled in the art. These results show that the compounds of the present disclosure are capable of inhibiting the biological action of IL-17A.

Human IL-17A Biochemical Assay

Compounds disclosed herein were tested for blocking of human IL-17A (Cat: C774, novoprotein) protein with its receptor human IL-17RA (Cat: C153, novoprotein) in an assay based on Homogeneous Time Resolved Fluorescence. 0.4 nM recombinant human IL-17A protein was pre-incubated with a serial dilution of compounds disclosed herein (maximum concentration is 10 uM, 2.7-fold serially diluted, 10 points) at room temperature for 3 hours in an assay buffer containing 20 mM HEPES, pH 7.5, 50 mM NaCl, 0.1% BSA, 0.2 mM DTT, 0.005% Tween 20. Then 0.3 nM recombinant human IL-17RA was added to plate and further incubated at room temperature for 1 hour. After that Mab Anti-6His Tb cryptate Gold (Cat: 61HI2TLB, Cisbio Bioassays) and MAb Anti Human IgG-XL665 (Cat: 61HFCXLB, Cisbio Bioassays) were added to plate and further incubated at room temperature for 1 hour. The HTRF signals (ex337 nm, em620 nm/665 nm) were read on BMG PHERAstar FSX instrument. The inhibition percentage of human IL-17A interaction with its receptor human IL-17RA in presence of increasing concentrations of compounds was calculated based on the ratio of fluorescence at 620 nm to that at 665 nm. The IC50 for each compound was derived from fitting the data to the four-parameter logistic equation by Dotmatics.

GROα Release Assay in Human Colorectal Adenocarcinoma Epithelial Cell

The purpose of the assay is to test the ability of a compound to neutralize IL17A proteins. IL17 can stimulate human epithelial cells to secrete GROα. The ability of one compound of the invention to neutralize IL-17-induced GROα secretion from the human colorectal adenocarcinoma epithelia cell line HT-29 is tested in this assay.

HT-29 cells (human colorectal adenocarcinoma epithelia cell, ATCC) were stimulated with IL-17A (Novoprotein, #C774) in final concentration of 10 ng/mL. The resultant GROα response was measured using an ELISA kit from Invitrogen (#88-52122). HT-29 cells were cultured in complete medium (McCoy's 5A medium+10% FBS) and maintained in a tissue culture flask using standard techniques. On day 1, detached the cell by using TrypLE (Gibco, #12605036) and used the complete medium to neutralize. The cells were centrifuged at 11,00 rmp for 4 minutes. Re-suspended the cell pellet in complete medium and seeded 50,000 HT-29 cells into the 96-well assay plate (Corning, 3599) at 135 μL complete medium per well. The cells were incubated for overnight, at 37° C./5% CO₂ to adherent the plate. On day 2, prepared a 4-fold serial dilution of the tested compound in DMSO. The highest concentration of the compound was 10 μM. Transferred 2 μL of the serial diluted compound from the serial dilution plate into the reagent plate which was contained 198 μL complete medium with 100 ng/mL IL-17A per well. The compounds were incubated with the IL-17A for 15 minutes. 15 μL mixtures from reagent plate were transferred into the cell assay plate. Incubated the plate at 37° C./5% CO₂ for 48 hours. After the incubation, on day 4, GROα level were measured with GROα ELISA as the manufacturer's instructions. 50 μL supernatant was collected form the assay plate to ELISA plate. ELISA plate was read at 450 nm on a microplate reader and compared to a standard calibration curve.

Data were processed using GraphPad Prism. GROα concentration was calculated from the standard curve. IC50 was determined using the equation log concentration (inhibitor) against response and fitted to four parameters.

	Biochemical
	assay	Cellular assay
	IL-17A/IL-	HT29 cell/		Biochemical assay	Cellular assay
	17RA	CXCL1		IL-17A/IL-17RA	HT29 cell/CXCL1
EX	IC50 (nM)	IC50 (nM)	EX	IC50 (nM)	IC50 (nM)
1	378.7	897.5	149	92	44.3
2	1,100	2,565	150	20	46.5
3	3,190	8,434	151	31	99.6
4	>10,000		152	10	31.0
5	410	352.7	153	95	258.2
6	17,000		154	28	71.4
7	51,000		155	129	210.9
8	>10,000		156	68.3	305.3
9	8,000	>10,000	157	37	398.3
10	19,000		158	123.1	48.5
11	1,700	6,522	159	53.2	186.7
12	13,000	>10,000	160	110.5	93.1
13	1,800	1,495	161	120.7	145.5
14	150	300.3	162	539.9	1,063
15	550	1,235	163	19.0	38.8
16	5,000		164	35.2	111.8
17	2,500	2,636	165	173.4	322.2
18	1,000	2,553	166	168.8	135
19	60	262.3	167	127	219.6
20	980	475.6	168	32.8	60.5
21	2,400		169	56.4	65.2
22	950	7,117	170	168.6	226.7
23	640	3,662	171	7.0	9.7
24	2,342		172	400.3	376.9
25	6,300		173		153.1
26	360	1,082	174	264	485.1
27	160	981.5	175	22.4	10.1
28	394	76.5	176	69.9	290.3
29	160	146.5	177	53.3	59.4
30	58	576.3	178	3,654	2,207
31	203	115.8	179	10.9	51.6
32	62	135.3	180	3,681
33	2,036		181	192.6	153.9
34	8,400		182	26.9	52.9
35	293	2,023	183	767.7	370.4
36	2,429		184	150.9	57.3
37	112	1,483	185	118.8	275.2
38	46	155.6	186	6.3	15.1
39	22.6	56.4	187	248.6	245.7
40	25	143.2	188	44.9	450.1
41	100	494.8	189	15.3	124.5
42	3,171		190	87.1	139.3
43	1,464	2,382	191	76.9	168.4
44	47	231.3	192	1,665	1,242
45	5,126		193	50.7	140.2
46	260	532.6	194	33.8	21.0
47	11	11.6	195	128.4	383.4
48	161	1,270	196	19.8	58.5
49	1,806		197	80.6	397
50	1,583		198	1,127	316.5
51	686	2,050	199	570.4	2,772
52	1,307		200	31.2	107.1
53	223	734.8	201	6.5	39.5
54	24	136.7	202	346	518.9
55	1,052	1,824	203	63.9	135.2
56	20	23.7	204	405.8	2,240
57	334	2,148	205	246.4	193.1
58	595	1,441	206	269.7	32.5
59	93	34.5	207	347.2	860.8
60	2,012		208	717.9	2,170
61	857	4,962	209	1,065	2,179
62	24	211.6	210	91.6	294.5
63	85	325.7	211	465	3,685
64	1,816		212	686.6	1,032
65	713	2,028	213	1,762	4,518
66	2,124		214	37.3	101.8
67	70	365	215	33.6	133.8
68	30	37.0	216	23.3	58.9
69	120	432.3	217	62.5	394
70	26	70.6	218	141.1	385.4
71	21	217.4	219	106.8	297.1
72	3,627		220	169	80.6
73	391		221	47.8	111.4
74	32	341.8	222	34.3	66.6
75	33	186.3	223	118	606.5
76	90	736	224	47.8	85.1
77	490		225	1,272	2,320
78	532		226	50.4	225.3
79	79	1,301	227	112	167.7
80	157	971.1	228	15.9	49.1
81	75	701.6	229	28.6	85.1
82	32	156.2	230	4,458	9,470
83	22	189.5	231	1,078	1,970
84	37	94.4	232	117.1	158
85	10,076		233	77.8	90.1
86	22	23.5	234	339.9	207
87	36	352.5	235	229.3	214
88	2,059		236	244.8	537.3
89	18	29.7	237	27.1	53.3
90	37	48.6	238	221.9	137
91	71	43.0	239	977.4	3,213
92	3,038		240	200.4	263.9
93	830		241	2,917	5,799
94	40	118	242	250.3	651.6
95	4,232		243	290	316.6
96	2,315		244	2,126	1,574
97	535	1,859	245	52.4	92.5
98	628	3,279	246	257.2	1,222
99	278	2,477	247	20.9	40.8
100	886	2,563	248	126.5	427
101	7.5	45.2	249	226	695.1
102	9.5	17.3	250	75.9	190
103	2,698			>10,000
104	12	23.6		139.9	271.2
105	15	55.5	251	1,514	1,510
106	48	202.4	252	828.9	1,165
107	25	34.5	253	355	330.6
108	5.8	42.3	254	178.1	318.4
109	3,453		255	165	665.8
110	15	76.5	256	50.2	82.0
111	55	111.5	257	938	2,503
112	41	180.7	258	107.9	208.6
113	53	456.6	259	1,020	1,973
114	73.9	57.2	260	>10,000
115	258	72.4	261	58	143.4
116	69.1	415.2	262	99.4	446.7
117	924.9	1,063	263	97.1	447.4
118	192	581.2	264	2,540
119	73	143.6	265	8,070
120	19	72.4	266	912	658.8
121	16	32.3	267	>10,000
122	10	13.0	268	88.1	248.1
123	441	61.6	269	416	1,068
124	19	32.5	270	200	350.3
125	5.6	25.8	271	268	1,385
126	72	3,955	272	295	650.3
127	698		273	34.7	66.1
128	89.8	277	274	42.4	67.6
129	44	119.2	275	61.3	133.4
130	19	59.6	276	573	1,464
131	5.5	14.9	277	560	1,284
132	66	177.9	278	333	122.5
133	320		279	64.8	69.1
134	311		280	17.3	48.1
135	186	244.8	281	16.5	67.4
136	108	279.1	282	33.7	95.3
137	413	1,490	283	32.5	34.6
138	53.1	101	284	268.5	353.6
139	10.0	21.9	285	71.4	90.2
140	277		286	143.6	429.9
141	16	41.1	287	61.5	221.8
142	107	197.2	288	109.6	408.4
143	163	771.5	289	24.5	81.4
144	48.6	181.7	290	18.6	60.3
			isomer 1
145	139	454.1	290	641.3	271.3
			isomer 2
146	203.6	767.7	291	1,552	1,060
147	22.4	61.8	292	287.3	206
			isomer 1
148	62	163.8	292	212.8	495.5
			isomer 2
			293	>10,000

It is to be understood that, if any prior art publication is referred to herein; such reference does not constitute an admission that the publication forms a part of the common general knowledge in the art in any country.

The disclosures of all publications, patents, patent applications and published patent applications referred to herein by an identifying citation are hereby incorporated herein by reference in their entirety.

Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is apparent to those skilled in the art that certain minor changes and modifications will be practiced. Therefore, the description and examples should not be construed as limiting the scope of the invention.

Claims

1. A compound of Formula (I):

2. The compound of claim 1, wherein the compound is selected from Formula (IIa)-(IIp):

3. The compound of claim 1, wherein the compound is selected from Formula (IIf1)-(IIf2):

4. The compound of claim 1, wherein the compound is selected from Formula (IIIa)-(IIIb):

5. The compound of claim 1, wherein the compound is selected from Formula (IVa)-(IVb):

6. The compound of claim 1, wherein the compound is selected from Formula (Va)-(Vc):

7. The compound claim 1, wherein the compound is VIa,

8. The compound claim 1, wherein the compound is VIIa or VIIb,

9. The compound of any one of the preceding claims, wherein Cy1 is a 5- or 6-membered aromatic ring, said ring comprising 0, 1 or 2 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with 0, 1, 2 or 3 substituents R3; preferably, Cy1 is phenyl, pyridyl, thiophenyl, imidazolyl, furanyl or pyrazolyl; each of phenyl, pyridyl, thiophenyl, imidazolyl, furanyl or pyrazolyl is optionally substituted with 0, 1 or 2 substituents R3.

10. The compound of any one of the preceding claims, wherein Cy2 a 4-, 5-, 6-, 7- or 8-membered saturated or partially or completely unsaturated ring, said ring comprising 0, 1, 2 or 3 heteroatoms independently selected from nitrogen or oxygen; said ring is substituted with at least one substituent R1 and/or R2; preferably, Cy2 a 5-, 6- or 7-membered saturated or partially or completely unsaturated ring, said ring comprising 0, 1 or 2 heteroatoms independently selected from nitrogen or oxygen; said ring is substituted with at least one substituent R1 and/or R2.

11. The compound of any one of the preceding claims, wherein

12. The compound of any one of the preceding claims, wherein Cy3 is a 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11- or 12-membered saturated or partially or completely unsaturated ring, said ring comprising 0, 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen or optionally oxidized sulfur; said ring is optionally substituted with 0, 1, 2, 3, 4 or 5 substituent R6; preferably, Cy3 is a 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11- or 12-membered saturated or partially or completely unsaturated ring, said ring is mono-cycle, bi-cycle or tri-cycle comprising 0, 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen or optionally oxidized sulfur; said ring is optionally substituted with 0, 1, 2, 3, 4 or 5 substituent R6;more preferably,

13. The compound of any one of the preceding claims, wherein R1 is independently selected from

14. The compound of any one of the preceding claims, wherein R15 is selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, —CN, —OR15a, —NR15aR15b, or —NR15aCOR15b; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and 3- to 8-membered heterocyclyl is optionally substituted with at least one substituent R15e; R15a and R15b are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C1-8haloalkyl, —C2-8alkenyl, —C2-8alkynyl, C1-8alkoxy-C1-8alkyl-, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, C6-C12aryl or 5- to 12-membered heteroaryl, each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, —C2-8alkenyl, —C2-8alkynyl, C1-8 alkoxy-C1-8alkyl-, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, C6-C12aryl and 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R15d;R15c and R15d, at each occurrence, are each independently —F, —Cl, —Br, —I, —OH, —CN, oxo, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C1-8haloalkyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —C3-C8halocycloalkyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 12-membered heteroaryl.

15. The compound of any one of the preceding claims, wherein R15 is selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, —CN, —OH, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy; preferably, R15 is selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl;more preferably, R15 is selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl;even more preferably, R15 is selected from hydrogen.

16. The compound of any one of the preceding claims, wherein R11a, R11b, R12a and R12b are each independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, —CN; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl and pyrazinyl is optionally substituted with at least one substituent R11e; R11e at each occurrence, is independently hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, oxo (═O), —OR11g, thioxo (═S), —SR11g, —CN, —SO2R11g, —SO2NR11gR11h, —COR11g, —CO2R11h, —CONR11gR11h, —NR11gR11h, —NR11gCOR11h, —NR11gCOR2R11h or —NR11gSOR2R11h; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl and pyrazinyl is optionally substituted with at least one substituent R11i;R11c, R11d, R11g and R11h are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C1-8haloalkyl, —C2-8alkenyl, —C2-8alkynyl, C1-8alkoxy-C1-8alkyl-, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl or 5- to 12-membered heteroaryl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C1-8 haloalkyl, —C2-8alkenyl, —C2-8alkynyl, C1-8alkoxy-C1-8alkyl-, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl and 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R11j;at each occurrence, R11i and R11j are each independently —F, —Cl, —Br, —I, —OH, —CN, oxo, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C1-8haloalkyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —C3-C8halocycloalkyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C1-8haloalkyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —C3-C8halocycloalkyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl is optionally substituted with at least one substituent —F, —Cl, —Br, —I, —OH, —CN, oxo, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C1-8haloalkyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —C3-C8halocycloalkyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 12-membered heteroaryl.

17. The compound of any one of the preceding claims, wherein R11a, R11b, R12a and R12b are each independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, —CN; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl and pyrazinyl is optionally substituted with at least one substituent R11e; R11e at each occurrence, is independently hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, vinyl, propenyl, allyl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-1-yl, pent-4-en-1-yl, pent-3-en-1-yl, pent-2-en-1-yl, pent-1-en-1-yl, hex-5-en-1-yl, hex-4-en-1-yl, hex-3-en-1-yl, hex-2-en-1-yl, hex-1-en-1-yl, hept-6-en-yl, hept-5-en-yl, hept-4-en-yl, hept-3-en-yl, hept-2-en-yl, hept-1-en-yl, oct-7-en-yl, oct-6-en-yl, oct-5-en-yl, oct-4-en-yl, oct-3-en-yl, oct-2-en-yl, oct-1-en-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl, pent-4-yn-1-yl, pent-3-yn-1-yl, pent-2-yn-1-yl, pent-1-yn-1-yl, hex-5-yn-1-yl, hex-4-yn-1-yl, hex-3-yn-1-yl, hex-2-yn-1-yl, hex-1-yn-1-yl, hept-6-yn-yl, hept-5-yn-yl, hept-4-yn-yl, hept-3-yn-yl, hept-2-yn-yl, hept-1-yn-yl, oct-7-yn-yl, oct-6-yn-yl, oct-5-yn-yl, oct-4-yn-yl, oct-3-yn-yl, oct-2-yn-yl, oct-1-yn-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, —OR11g or —CN;R11g is independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl;preferably, R11a, R11b, R12a and R12b are each independently selected from H, —CH3, —CF3, —CH2CH3, —CH2CF3, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, pyrrolidinyl, tetrahydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, benzyl, vinyl, propenyl, allyl, but-3-en-1-yl, ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, but-3-yn-1-yl, but-2-yn-1-yl, but-1-yn-1-yl,

18. The compound of any one of the preceding claims, wherein (R11a and R11b), (R12a and R12b), (R11aand R12a), (R11a and R12b), (R11b and R12a) or (R11b and R12b) together with the carbon atoms to which they are attached, form a 3-, 4-, 5-, 6- or 8-membered unsaturated or saturated ring, said ring comprising 0, 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R11f; R11f, at each occurrence, is independently hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, C6-C12aryl, 5- to 12-membered heteroaryl, oxo (═O), —OR11g, thioxo (═S), —SR11g, —CN, —SO2R11g, —SO2NR11gR11h, —COR11g, —CO2R11h, CONR11gR11h, —NR11gR11h, —NR11gCOR11h, —NR11gCO2R11h or —NR11gSO2R11h;R11g and R11h are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C2-8alkenyl, —C2-8alkynyl, C1-8alkoxy-C1-8alkyl-, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, C6-C12aryl or 5- to 12-membered heteroaryl;at each occurrence, R11i is independently —F, —Cl, —Br, —I, —OH, —CN, oxo, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C1-8haloalkyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —C3-C8halocycloalkyl, 3- to 8-membered heterocyclyl, —C6-C12aryl, or 5- to 12-membered heteroaryl;preferably, (R11a and R11b), (R12a and R12b), (R11a and R12a), (R11a and R12b), (R11b and R12a) or (R11b and R12b) together with the carbon atoms to which they are attached, form a 3-, 4-, 5-, 6- or 8-membered unsaturated or saturated ring;more preferably, (R11a and R11b), (R12a and R12b), (R11a and R12a), (R11a and R12b), (R11b and R12a) or (R11b and R12b) together with the carbon atoms to which they are attached, form a 3-, 4-, 5-, 6- or 8-membered saturated ring;

19. The compound of any one of the preceding claims, wherein R13, R14a and R14b are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or 3- to 8-membered heterocyclyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or 3- to 8-membered heterocyclyl is optionally substituted with at least one substituent R13a; R13a, at each occurrence, is independently halogen, —OH, —CN, oxo, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —C1-8haloalkyl, —C1-8alkoxy, —C2-8alkenyl, —C2-8alkynyl, —C3-C8halocycloalkyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 12-membered heteroaryl;preferably, R13, R14a and R14b are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or 3- to 8-membered heterocyclyl;more preferably, R13 is hydrogen, methyl, ethyl, propyl or butyl; R14a and R14b are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or 3- to 8-membered heterocyclyl;even more preferably, R13 is hydrogen; R14a and R14b are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl.

20. The compound of any one of the preceding claims, wherein R1 is selected from

21. The compound of any one of the preceding claims, wherein R2 is independently selected from H, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, —CN, —COR2a, —CO2R2a, —CONR2aR2b, —NR2aR2b, —NR2aCOR2b, each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl and imidazopyridinyl is optionally substituted with at least one substituent R2c; R2a and R2b are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl is optionally substituted with at least one substituent R2d; orR2a and R2b together with the carbon atoms to which they are attached, form a 3-, 4-, 5-, 6-, 7- or 8-membered unsaturated or saturated ring, said ring comprising 0, 1, 2, 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R2d;R2c and R2d, at each occurrence, are each independently hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, oxo (═O), —OR2e, —SR2e, —CN, —COR2e, —CO2R2e, —CONR2eR2f, —NR2eR2f, —NR2eCOR2f or —NR2eCO2R2f; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl is optionally substituted with at least one substituent R2g;R2e and R2fare each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C1-8alkoxy-C1-8 alkyl-, —C1-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl or 5- to 12-membered heteroaryl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C1-8alkoxy-C1-8alkyl-, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl or 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R2h R2g and R2h, at each occurrence, are each independently —F, —Cl, —Br, —I, —OH, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C1-8haloalkyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C1-8alkoxy-C1-8alkyl-, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —C3-C8halocycloalkyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 12-membered heteroaryl.

22. The compound of any one of the preceding claims, wherein R2 is independently selected from H, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, —CN, —COR2a, —CO2R2a or —CONR2aR2b, each of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl is optionally substituted with at least one substituent R2c; R2a and R2b are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, aziridinyl, azetidinyl, pyrrolidinyl, dihydropyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl is optionally substituted with at least one substituent R2d; orR2a and R2b together with the carbon atoms to which they are attached, form a 3-, 4-, 5- or 6-membered unsaturated or saturated ring, said ring comprising 0 or 1 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R2d;R2c and R2d, at each occurrence, are each independently hydrogen (H or D), —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, —OR2e, —CN or —NR2eR2f; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl is optionally substituted with at least one substituent R2g;R2e and R2fare each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl is optionally substituted with at least one substituent R2hR2g and R2h, at each occurrence, are each independently —F, —Cl, —Br, —I, —OH, methyl, ethyl, propyl, butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;preferably, R2 is

23. The compound of any one of the preceding claims, wherein R3 is independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or —CN, wherein each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl is optionally substituted with at least one substituent selected from —F, —Cl, —Br, —I, —OH, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C1-8alkoxy-C1-8alkyl-, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, —C6-C12aryl, or 5- to 12-membered heteroaryl; preferably, R3 is independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or —CN;more preferably, R3 is independently selected from hydrogen, —F, —Cl, —Br, —I.

24. The compound of any one of the preceding claims, wherein R4 is oxo (═O).

25. The compound of any one of the preceding claims, wherein R3 and R4 together with the carbon atoms to which they are attached, form a 5- to 6-membered aromatic ring, said ring comprising 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R3a; R3a is independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —CN, wherein each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl is optionally substituted with at least one substituent selected from —F, —Cl, —Br, —I, —OH, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C1-8alkoxy-C1-8alkyl-, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, —C6-C12aryl, or 5- to 12-membered heteroaryl.

26. The compound of any one of the preceding claims, wherein R5 is phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, —COR5a, —CO2R5a, or —CONR5aR5b, wherein each of phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl is optionally substituted with at least one substituent R5c; R5a and R5b are each independently selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, oxadiazolyl, triazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, oxadiazolyl, triazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl is optionally substituted with at least one substituent Rd; orR5a and R5b together with the nitrogen atom to which they are attached, form a 3-, 4-, 5-, 6-, 7- or 8-membered unsaturated or saturated ring, said ring comprising 0, 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; said ring is optionally substituted with at least one substituent R5d;R5c and R5d, at each occurrence, are independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, oxo (═O), —OR5e, —SR5e, —CN, —COR5e, —CO2R5e, —CONR5eR5f, —NR5eR5f, —NR5eCOR5f or —NR5eCO2R5f; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl is optionally substituted with at least one substituent R5g;R5e and R5fare each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C1-8alkoxy-C1-8 alkyl-, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C1-8alkoxy-C1-8alkyl-, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl is optionally substituted with at least one substituent R5h;R5g and R5h are each independently selected from halogen, —OH, —CN, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C1-8 alkoxy-C1-8alkyl-, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl or 5- to 12-membered heteroaryl.

27. The compound of any one of the preceding claims, wherein R5 is pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl, wherein each of pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, is optionally substituted with at least one substituent R5c; R5c, at each occurrence, is independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl;preferably, R5 is benzooxazolyl;more preferably, R5 is

28. The compound of any one of the preceding claims, wherein R5 is —COR5a, —CO2R5a or —CONR5aR5b; wherein R5a and R5b are each independently selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, oxadiazolyl, triazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl is optionally substituted with at least one substituent R5d;R5d, at each occurrence, is independently selected from hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl, imidazopyridinyl, —OR5e or —CN; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl is optionally substituted with at least one substituent R5g;R5e is selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzoimidazolyl, imidazopyridazinyl or imidazopyridinyl is optionally substituted with at least one substituent R5h;R5g and R5h are each independently selected from halogen, —OH, —CN, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl or 5- to 12-membered heteroaryl;preferably, R5

29. The compound of any one of the preceding claims, wherein R6 is H, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, —CN, —OR6a, —NR6aR6b, —COR6a, —CO2R6a, —CONR6aR6b, —COR6a or —NR6aCOR6b, each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl is optionally substituted with at least one substituent R6C; R6a and R6b are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl or 5- to 12-membered heteroaryl; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl or 5- to 12-membered heteroaryl is optionally substituted with at least one substituent Rid;R6c, at each occurrence, is independently hydrogen, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, 5- to 12-membered heteroaryl, oxo (═O), —OR6e, —SR6e, —CN, —COR6e, —CO2R6e, —CONR6eR6f, —NR6eR6f, —NR6eCOR6f or —NR6eCO2R6f; each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R6g;R6e and R6f are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C1-8alkoxy-C1-8 alkyl-, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl or 5- to 12-membered heteroaryl;R6d and R6g are each independently selected from —F, —Cl, —Br, —I, —OH, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C1-8alkoxy-C1-8alkyl-, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 12-membered heteroaryl;

30. The compound of any one of the preceding claims, wherein R6 is H, —F, —Cl, —Br, —I, methyl, —CF3, ethyl, —CH2CF3, —CF2CH3, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, furanyl, thiophenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, —CN, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy,

31. The compound of any one of the preceding claims, wherein R9 and R10 are each independently selected from H, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl or 5- to 12-membered heteroaryl, each of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl or 5- to 12-membered heteroaryl is optionally substituted with at least one substituent R9a; R9a, at each occurrence, is independently halogen, —OH, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, C1-8alkoxy-C1-8alkyl-, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 12-membered heteroaryl;preferably, R9 and R10 are each independently selected from H, —F, —Cl, —Br, —I, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, —C2-8alkenyl, —C2-8alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl or 5- to 12-membered heteroaryl;more preferably, R9 and R10 are each independently selected from H, methyl, ethyl, propyl, butyl, pentyl, cyclopropyl, cyclobutyl, cyclopentyl;more preferably, R9 and R10 are each independently selected from H, cyclopropyl.

32. The compound of any one of the preceding claims, wherein the compound is selected from

33. A pharmaceutical composition comprising a compound of any one of claims 1-32 or a pharmaceutically acceptable salt, stereoisomer, tautomer or prodrug thereof, together with a

34. A method of decreasing IL-17 activity by inhibition, which comprises administering to an individual the compound according to any one of claims 1-32, or a pharmaceutically acceptable salt thereof, including the compound of formula (I) or the specific compounds exemplified herein.

35. The method of claim 34, wherein the disease is selected from cancer.

36. Use of a compound of any one of claims 1-32 or a pharmaceutically acceptable salt, stereoisomer, tautomer or prodrug thereof in the preparation of a medicament for treating a disease that can be affected by IL-17.

37. The use of claim 36, wherein the disease is autoimmune disease or inflammatory disease.

38. The use of claim 37, wherein the disease is chronic inflammation, psoriasis, spondylarthritis, rheumatoid arthritis or multiple sclerosis.