Acylsemicarbazides as cyclin dependent kinase inhibitors useful as anti-cancer and anti-proliferative agents

Abstract

The present invention relates to the synthesis of a new class of indeno[1,2-c]pyrazol-4-ones of formula (I): that are potent inhibitors of the class of enzymes known as cyclin dependent kinases, which relate to the catalytic subunits cdk1-7 and their regulatory subunits know as cyclins A-G.This invention also provides a novel method of treating cancer or other proliferative diseases by administering a therapeutically effective amount of one of these compounds or a pharmaceutically acceptable salt form thereof. Alternatively, one can treat cancer or other proliferative diseases by administering a therapeutically effective combination of one of the compounds of the present invention and one or more other known anti-cancer or anti-proliferative agents.

Description

FIELD OF THE INVENTION

This invention relates generally to novel 5-substituted-indeno[1,2-c]pyrazol-4-ones which are useful as cyclin dependent kinase (cdk) inhibitors, pharmaceutical compositions comprising the same, methods for using the same for treating proliferative diseases, and intermediates and processes for making the same.

BACKGROUND OF THE INVENTION

One of the most important and fundamental processes in biology is the division of cells mediated by the cell cycle. This process ensures the controlled production of subsequent generations of cells with defined biological function. It is a highly regulated phenomenon and responds to a diverse set of cellular signals both within the cell and from external sources. A complex network of tumor promoting and suppressing gene products are key components of this cellular signaling process. Over expression of the tumor promoting components or the subsequent loss of the tumor suppressing products will lead to unregulated cellular proliferation and the generation of tumors (Pardee, Science 246:603-608, 1989).

Cyclin dependent kinases (cdks) play a key role in regulating the cell cycle machinery. These complexes consist of two components: a catalytic subunit (the kinase) and a regulatory subunit (the cyclin). To date, six kinase subunits (cdk 1-7) have been identified along with several regulatory subunits (cyclins A-H). Each kinase associates with a specific regulatory partner and together make up the active catalytic moiety. Each transition of the cell cycle is regulated by a particular cdk complex: G1/S by cdk2/cyclin E, cdk4/cyclin D1 and cdk6/cyclinD/2; S/G2 by cdk2/cyclin A and cdk1/cyclin A; G2/M by cdk1/B. The coordinated activity of these kinases guides the individual cells through the replication process and ensures the vitality of each subsequent generation (Sherr, Cell 73:1059-1065, 1993; Draetta, Trends Biochem. Sci. 15:378-382, 1990)

An increasing body of evidence has shown a link between tumor development and cdk related malfunctions. Over expression of the cyclin regulatory proteins and subsequent kinase hyperactivity have been linked to several types of cancers (Jiang, Proc. Natl. Acad. Sci. USA 90:9026-9030, 1993; Wang, Nature 343:555-557, 1990). More recently, endogenous, highly specific protein inhibitors of cdks were found to have a major affect on cellular proliferation (Kamb et al, Science 264:436-440, 1994; Beach, Nature 336:701-704, 1993). These inhibitors include p16 INK4 (an inhibitor of cdk4/D1), p21 CIP1 (a general cdk inhibitor), and p27 KIP1 (a specific cdk2/E inhibitor). A recent crystal structure of p27 bound to cdk2/A revealed how these proteins effectively inhibit the kinase activity through multiple interactions with the cdk complex (Pavletich, Nature 382:325-331, 1996). These proteins help to regulate the cell cycle through specific interactions with their corresponding cdk complexes. Cells deficient in these inhibitors are prone to unregulated growth and tumor formation.

This body of evidence has led to an intense search for small molecule inhibitors of the cdk family as an approach to cancer chemotherapy.

A series of indeno[1,2-c]pyrazoles having anticancer activity are described in JP 60130521 and JP 62099361 with the following generic structure:

A series of indeno[1,2-c]pyrazoles having herbicidal activity are described in GB 2223946 with the following generic structure:

A series of 1-(6′-substituted-4′-methylquinol-2′-yl)-3-methylindeno[1,2-c]pyrazoles having CNS activity are described by Quraishi, Farmaco 44:753-8, 1989 with the following generic structure:

There is a continuing unmet need for cdk inhibitors with which to treat proliferative diseases.

SUMMARY OF THE INVENTION

The present invention describes a novel class of indeno[1,2-c]pyrazol-4-ones or pharmaceutically acceptable salt forms thereof that are potent inhibitors of the class of enzymes known as cyclin dependent kinases, which relate to the catalytic subunits cdk 1-7 and their regulatory subunits know as cyclins A-H.

The present invention is also directed to a novel method of treating cancer or other proliferative diseases by administering a therapeutically effective amount of one of these compounds or a pharmaceutically acceptable salt form thereof.

A novel method of treating cancer or other proliferative diseases, which comprises administering a therapeutically effective combination of one of the compounds of the present invention and one or more other known anti-cancer or anti-proliferative agents is also described herein.

The present invention also describes compounds of formula (I):

wherein R 1 , R 2 and X are defined below or pharmaceutically acceptable salts thereof as cyclin dependent kinase inhibitors.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The invention pertains to novel cyclin dependent kinase inhibitors (cdks) and specifically, but not exclusively, as inhibitors of cdk/cyclin complexes. The inhibitors of this invention are indeno[1,2-c]pyrazol-4-one analogs. Certain analogs were selective for their activity against cdks and their cyclin bound complexes and were less active against other known serine/threonine kinases such as Protein Kinase A (PKA) and Protein Kinase C (PKC). In addition, these inhibitors were less active against tyrosine kinases such as c-Ab1.

As described herein, the inhibitors of this invention are capable of inhibiting the cell-cycle machinery and consequently would be useful in modulating cell-cycle progression, which would ultimately control cell growth and differentiation. Such compounds would be useful for treating subjects having disorders associated with excessive cell proliferation, such as the treatment of cancer, psoriasis, immunological disorders involving unwanted leukocyte proliferation, in the treatment of restinosis and other smooth muscle cell disorders, and the like.

The present invention, in a first embodiment, describes a novel compound of formula (I):

or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:

X is selected from the group: O, S, and NR;

R is selected from the group: H, C 1-4 alkyl, and NR 5 R 5a ;

R 1 is selected from the group: H, C 1-10 alkyl substituted with 0-3 R c , C 2-10 alkenyl substituted with 0-3 R c , C 2-10 alkynyl substituted with 0-3 R c , C 1-10 alkoxy, —NHR 4 , C 3-10 carbocycle substituted with 0-5 R a , and 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R b ;

R 2 is selected from the group: H, C 1-10 alkyl substituted with 0-3 R c , C 2-10 alkenyl substituted with 0-3 R c , C 2-10 alkynyl substituted with 0-3 R c , —(CF 2 ) m CF 3 , C 3-10 carbocycle substituted with 0-5 R a , and 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R b ;

R 3 is selected from the group: H, halo, —CN, NO 2 , C 1-4 haloalkyl, NR 5 R 5a , NR 5 NR 5 R 5a , NR 5 C(O)OR 5 , NR 5 C(O)R 5 , ═O, OR 5 , COR 5 , CO 2 R 5 , CONR 5 R 5a , NHC(O)NR 5 R 5a , NHC(S)NR 5 R 5a , SO 2 NR 5 R 5a , SO 2 R 5b , C 1-4 alkyl, phenyl, benzyl, C 1-4 alkyl substituted with 1-3 R c , C 5-10 alkyl substituted with C 2-10 alkenyl optionally substituted with 0-3 R 6 , C 2-10 alkynyl substituted with 0-3 R 6 , —(CF 2 ) m CF 3 , C 3-10 carbocycle substituted with 0-5 R 6 , and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R 6 ; and

provided that if R 3 is phenyl, it is substituted with 1-5 R a ;

R 4 is independently at each occurrence selected from the group: H, —CN, C 1-4 alkyl, C 1-4 haloalkyl, NR 3 R 3a , NR 3 C(O)OR 3 , NR 3 C(O)R 3 , OR 3 , COR 3 , CO 2 R 3 , CONR 3 R 3a , NHC(O)NR 3 R 3a , NHC(S)NR 3 R 3a , SO 2 NR 3 R 3a , SO 2 R 3b , C 3-10 carbocycle substituted with 0-5 R a , and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R 3 ;

provided that at least one R 3 is present and that this R 3 is selected from the group: C 1-4 alkyl substituted with 1-3 R 6 , C 5-10 alkyl substituted with C 2-10 alkenyl optionally substituted with 0-3 R 6 , C 2-10 alkynyl substituted with 0-3 R 6 , —(CF 2 ) m CF 3 , C 3-10 carbocycle substituted with 0-5 R 6 , and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R 6 ;

R a is independently at each occurrence selected from the group: halo, —CN, N 3 , NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, NR 3 R 3a , ═O, OR 3 , COR 3 , CO 2 R 3 , CONR 3 R 3a , NHC(O)NR 3 R 3a , NHC(S)NR 3 R 3a , NR 3 C(O)OR 3 , NR 3 C(O)R 3 , SO 2 NR 3 R 3a , SO 2 R 3b , and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S;

alternatively, when two R 2 , are present on adjacent carbon atoms they combine to form —OCH 2 O— or —OCH 2 CH 2 O—;

R b is independently at each occurrence selected from the group: halo, —CN, NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, NR 3 R 3a , NR 3 C(O)OR 3 , NR 3 C(O)R 3 , OR 3 , COR 3 , CO 2 R 3 , CONR 3 R 3a , NHC(O)NR 3 R 3a , NHC(S)NR 3 R 3a , SO 2 NR 3 R 3a , and SO 2 R 3b ;

R c is independently at each occurrence selected from the group: halo, —CN, NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, NR 3 R 3a , NR 5 NR 5 R 5a , NR 3 C(O)OR 3 , NR 3 C(O)R 3 , ═O, OR 3 , COR 3 , CO 2 R 3 , CONR 3 R 3a , NHC(O)NR 3 R 3a , NHC(S)NR 3 R 3a , SO 2 NR 3 R 3a , SO 2 R 3b , C 3-10 carbocycle substituted with 0-5 R a , and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R 3 ;

R 3a is selected from the group: H, C 1-4 alkyl, phenyl, and benzyl;

alternatively, R 3 and R 3a , together with the nitrogen atom to which they are attached, form a heterocycle having 4-8 atoms in the ring containing an additional 0-1 N, S, or O atom and substituted with 0-3 R 3c ;

R 3b is selected from the group: H, C 1-4 alkyl, phenyl, and benzyl;

R 3c is independently at each occurrence selected from the group: halo, —CN, N 3 , NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, NR 3 R 3b , ═O, OR 3 , COR 3 , CO 2 R 3 , CONR 3 R 3 b , NHC(O)NR 3 R 3 b , NHC(S)NR 3 R 3 b , NR 3 C(O)OR 3 , NR 3 C(O)R 3 , SO 2 NR 3 R 3 b , SO 2 R 3b , and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S;

R 5 is independently selected from the group: H, C 1-4 alkyl, phenyl and benzyl;

R 5a is independently selected from the group: H, C 1-4 alkyl, phenyl and benzyl;

R 5b is independently selected from the group: H, C 1-4 alkyl, phenyl and benzyl;

R 6 is independently at each occurrence selected from the group: halo, —CN, NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, NR 5 R 5 , NR 5 NR 5 R 5a , NR 5 C(O)OR 5 , NR 5 C(O)R 5 , ═O, OR 5 , COR 5 , CO 2 R 5 , CONR 5 R 5a , NHC(O)NR 5 R 5a , NHC(S)NR 5 R 5a , SO 2 NR 5 R 5a , SO 2 R 5b , C 3-10 carbocycle substituted with 0-5 R 5 , and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R 5 ; and

m is selected from 0, 1, 2, and 3.

In another embodiment of the present invention, the compounds of formula (I) are selected from:

3-(4-methoxyphenyl)-5-(2-benzoylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-isonicotinoylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-nictinoylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-(3,4-dihydroxybenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5(2-(4-hydroxybenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-(3-aminobenzoyl) hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-(4-aminobenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-(2-aminobenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-(4-N,N-dimethylaminobenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-phenethylacetylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-(2-hydroxybenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one; and

3-(4-methoxyphenyl)-5-(2-methoxycarbonylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

1-[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-3-morpholin-4-yl-urea;

[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-urea;

1-(2-amino-cyclohexyl)-3-[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-urea;

2-(4-aminomethyl-piperidin-1-yl)-N-[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-acetamide;

1-[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-3-morpholin-4-yl-urea.

or pharmaceutically acceptable salt form thereof.

Another embodiment of the present invention is a pharmaceutical composition comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of formula (I).

Another embodiment of the present invention is a method of treating cancer and proliferative diseases comprising: administering to a host in need of such treatment a therapeutically effective amount of a compound of formula (I), or a pharmaceutically effective salt form thereof.

DEFINITIONS

As used herein, the following terms and expressions have the indicated meanings. The compounds of the present invention may contain an asymmetrically substituted carbon atom, and may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. All chiral, diastereomeric, racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomer form is specifically indicated.

The term “alkyl” is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, and s-pentyl. In addition, the term is intended to include both unsubstituted and substituted alkyl groups, the latter referring to alkyl moieties having one or more hydrogen substituents replaced by, but not limited to halogen, hydroxyl, carbonyl, alkoxy, ester, ether, cyano, phosphoryl, amino, imino, amido, sulfhydryl, alkythio, thioester, sulfonyl, nitro, heterocyclo, aryl or heteroaryl. It will also be understood by those skilled in the art that the substituted moieties themselves can be substituted as well when appropriate.

The terms “halo” or “halogen” as used herein refer to fluoro, chloro, bromo and iodo. The term “aryl” is intended to mean an aromatic moiety containing the specified number of carbon atoms, such as, but not limited to phenyl, indanyl or naphthyl. The terms “cycloalkyl” and “bicycloalkyl” are intended to mean any stable ring system, which may be saturated or partially unsaturated. Examples of such include, but are not limited to, cyclopropyl, cyclopentyl, cyclohexyl, norbornyl, bicyclo[2.2.2]nonane, adamantly, or tetrahydronaphthyl (tetralin).

As used herein, “carbocycle” or “carbocyclic residue” is intended to mean any stable 3- to 7-membered monocyclic or bicyclic or 7- to 13-membered bicyclic or tricyclic, any of which may be saturated, partially unsaturated, or aromatic. Examples of such carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, cyclooctyl,; [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane (decalin), [2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, or tetrahydronaphthyl (tetralin).

As used herein, the term “heterocycle” or “heterocyclic system” is intended to mean a stable 5- to 7-membered monocyclic or bicyclic or 7- to 10-membered bicyclic heterocyclic ring which is saturated partially unsaturated or unsaturated (aromatic), and which consists of carbon atoms and from 1 to 4 heteroatoms independently selected from the group consisting of N, O and S and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The nitrogen and sulfur heteroatoms may optionally be oxidized. The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom which results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. If specifically noted, a nitrogen in the heterocycle may optionally be quaternized. It is preferred that when the total number of S and O atoms in the heterocycle exceeds 1, then these heteroatoms are not adjacent to one another. It is preferred that the total number of S and O atoms in the heterocycle is not more than 1. As used herein, the term “aromatic heterocyclic system” is intended to mean a stable 5- to 7-membered monocyclic or bicyclic or 7- to 10-membered bicyclic heterocyclic aromatic ring which consists of carbon atoms and from 1 to 4 heterotams independently selected from the group consisting of N, O and S. It is preferred that the total number of S and O atoms in the aromatic heterocycle is not more than 1.

Examples of heterocycles include, but are not limited to, 1H-indazole, 2-pyrrolidonyl, 2H,6H-1,5,2-dithiazinyl, 2H-pyrrolyl, 3H-indolyl, 4-piperidonyl, 4aH-carbazole, 4H-quinolizinyl, 6H-1,2,5-thiadiazinyl, acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl, carbazolyl, 4aH-carbazolyl, b-carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl., oxazolyl, oxazolidinylperimidinyl, phenanthridinyl, phenanthrolinyl, phenarsazinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, piperidonyl, 4-piperidonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, carbolinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, xanthenyl. Preferred heterocycles include, but are not limited to, pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, indolyl, benzimidazolyl, 1H-indazolyl, oxazolidinyl, benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl, or isatinoyl. Also included are fused ring and spiro compounds containing, for example, the above heterocycles.

As used herein, “pharmaceutically acceptable salts” refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, and the like.

The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 18th ed., Mack Publishing Company, Easton, Pa., 1990, p. 1445, the disclosure of which is hereby incorporated by reference.

The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication commensurate with a reasonable benefit/risk ratio.

“Prodrugs”, as the term is used herein, are intended to include any covalently bonded carriers which release an active parent drug of the present invention in vivo when such prodrug is administered to a mammalian subject. Since prodrugs are known to enhance numerous desirable qualities of pharmaceuticals (i.e., solubility, bioavailability, manufacturing, etc.) the compounds of the present invention may be delivered in prodrug form. Thus, the present invention is intended to cover prodrugs of the presently claimed compounds, methods of delivering the same, and compositions containing the same. Prodrugs of the present invention are prepared by modifying functional groups present in the compound in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compound. Prodrugs include compounds of the present invention wherein a hydroxy, amino, or sulfhydryl group is bonded to any group that, when the prodrug of the present invention is administered to a mammalian subject, it cleaves to form a free hydroxyl, free amino, or free sulfydryl group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate, and benzoate derivatives of alcohol and amine functional groups in the compounds of the present invention.

“Substituted” is intended to indicate that one or more hydrogens on the atom indicated in the expression using “substituted” is replaced with a selection from the indicated group(s), provided that the indicated atom's normal valency is not exceeded, and that the substitution results in a stable compound. When a substituent is keto (i.e., ═O) group, then 2 hydrogens on the atom are replaced.

As used herein, the term “anti cancer” or “anti-proliferative” agent includes, but is not limited to, altretamine, busulfan, chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan, thiotepa, cladribine, fluorouracil, floxuridine, gemcitabine, thioguanine, pentostatin, methotrexate, 6-mercaptopurine, cytarabine, carmustine, lomustine, streptozotocin, carboplatin, cisplatin, oxaliplatin, iproplatin, tetraplatin, lobaplatin, JM216, JM335, fludarabine, aminoglutethimide, flutamide, goserelin, leuprolide, megestrol acetate, cyproterone acetate, tamoxifen, anastrozole, bicalutamide, dexamethasone, diethylstilbestrol, prednisone, bleomycin, dactinomycin, daunorubicin, doxirubicin, idarubicin, mitoxantrone, losoxantrone, mitomycin-c, plicamycin, paclitaxel, docetaxel, topotecan, irinotecan, 9-amino camptothecan, 9-nitro camptothecan, GS-211, etoposide, teniposide, vinblastine, vincristine, vinorelbine, procarbazine, asparaginase, pegaspargase, octreotide, estramustine, hydroxyurea.

SYNTHESIS

The compounds of the present invention can be synthesized using the methods described below, together with synthetic methods known in the art of synthetic organic chemistry, or variations thereon as appreciated by those skilled in the art. Preferred methods include, but are not limited to, those methods described below. Each of the references cited below are hereby incorporated herein by reference.

An approach to preparing indeno[1,2-c]pyrazol-4-ones is presented in Scheme 1 and can be used to prepare compounds of the present invention. The nitro group of dimethyl 3-nitrophthalate was reduced to the amine using catalytic hydrogenation. The aniline was acylated using acetic anhydride and pyridine as a base. A mixture of the resulting acetamide 2 and an acetophenone were treated with a strong base in an appropriate solvent at elevated temperature to give the desired triketone 3. Additional means of preparing triketones are known to one skilled in the art as described in Kilgore et al, Industrial and Engineering Chemistry 34:494-497, 1946, the contents of which are hereby incorporated herein by reference. The triketone was treated with hydrazine at elevated temperature in an appropriate solvent to give the indeno[1,2-c]pyrazol-4-one ring system. Additional means of preparing indeno[1,2-c]pyrazol-4-ones are known to one skilled in the art as described in Lemke et al., J. Heterocyclic Chem. 19:1335-1340, 1982; Mosher and Soeder, J. Heterocyclic Chem. 8:855-59, 1971; Hrnciar and Svanygova Collect. Czech. Chem. Commun. 59:2734-40, 1994 the contents of which are hereby incorporated herein by reference. The amide was deacylated by heating with a strong acid in an appropriate solvent to give aniline 4. This aniline was acylated under standard conditions using an acid chloride in an appropriate solvent to give the desired product 5.

An alternative method for making compounds of the present invention is shown in Scheme 2. The intermediate triketone 3 can be deacylated with strong acid and reacylated with an appropriate acid chloride using methods known to those skilled in the art. Subsequently, triketone 6 can the be converted to the indeno[1,2-c]pyrazol-4-one ring system using the same conditions described previously in Scheme 1.

Another method for preparing the triketones 6 of Scheme 2 employs the condensation of a 1,3-diketone 6a with 3-nitrophthalic anhydride as described in Rotberg and Oshkaya, Zh. Organ. Khim. 8:84-87, 1972; Zh. Organ. Khim. 9:2548-2550, 1973, the contents of which are hereby incorporated herein by reference. The 1,3-diketones, when not commercially available can be readily prepared by one skilled in the art by the acetylation or trifluoroacetylation of the requisite methyl ketone, R 1 COCH 3 . Reduction of the nitro derivative 6b to the aniline 6c can be accomplished in a variety of ways including catalyic hydrogenation, treatment with zinc or iron under acidic conditions, or treatment with other reducing agents such as sodium dithionite or stannous chloride. Subsequently the aniline 6c can be converted to the indeno[1,2-c]pyrazol-4-ones of this invention by acylation followed by treatment with hydrazine as described previously in Scheme 2.

Another method for making the indeno[1,2-c]pyrazol-4-one ring system is shown in Scheme 4. Dimethyl hydrazine was reacted with 3-acetylpyridine with no solvent to give the hydrazone 7. This was treated in a similar fashion as described in Scheme 1 to give the desired intermediate 8. Additional means of preparing similar intermediates are known to one skilled in the art as described in Rappoport, J. Org. Chem. 49:2948-2953, 1984, the contents of which are hereby incorporated herein by reference. This intermediate was carried through the sequence in a similar fashion as described in Scheme 1.

Another approach to preparing indeno[1,2-c]pyrazol-4-ones is presented in Scheme 5 and can be used to prepare compounds of the present invention. Treating the intermediate 5-aminoindeno[1,2-c]pyrazol-4-one with 2-(trimethylsilyl) ethoxymethylmethyl chloride (SEMCl) and a suitable base in an inert solvent under reflux gives the SEM protected intermediate. The aniline is converted to the carbamate with phenylchloroformate using methods known to those skilled in the art. This intermediate is reacted with carbaztes in DMSO at elevated temperatures and then the SEM group is removed by treating with acid in a polar protic solvent to give the desired acylsemicarbazide-containing indenopyrazole analogs.

Other features of the invention will become apparent during the following descriptions of exemplary embodiments which are given for illustration of the invention and are not intended to be limiting thereof.

EXAMPLES

Abbreviations used in the Examples are defined as follows: “°C.” for degrees Celsius, “CIMS” for chemical ionization mass spectroscopy, “eq” for equivalent or equivalents, “g” for gram or grams, “h” for hour or hours, “mg” for milligram or milligrams, “mL” for milliliter or milliliters, “mmol” for millimolar, “M” for molar, “min” for minute or minutes, “p-TsOH” for para-toluenesulphonic acid, “DMF” for dimethylformamide, and “TFA” for trifluoroacetic acid.

Example I

Preparation of 3-(4-methoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 2 from Dimethyl 3-nitrophthalate.

A solution of dimethyl 3-nitrophthalate (25 g, 105 mmol) in methanol (100 mL) was treated with 5% Pd/C (2.5 g) and hydrogenated on a Parr Shaker at 50 psi for 2 h. The solution was filtered (Celite), the filtrate collected and the solvent removed at reduced pressure. The residue was dissolved in acetic anhydride (20 mL) treated with pyridine (0.05 mL) and heated to 80° C. for 1 min. The reaction was cooled and stirred at 25° C. for 2 h. The solvent was removed at reduced pressure and the residue recrystallized from ethanol to give the product as a white solid (21 g, 79%). mp 104-105° C.; CIMS m/e calc'd for C 12 H 14 NO 5 : 252.0872, found 252.0888; Analysis calc'd for C 12 H 13 NO 5 : C, 57.37; H, 5.22; N, 5.58; found: C, 57.67; H, 5.29; N, 5.77.

Step 2. Synthesis of Triketone 11 from 2.

A solution of 2 (1 g, 4.0 mmol) in dry DMF (2 mL) was treated with sodium hydride (0.15 g, 60% suspension in oil, 0.4 mmol) in one portion. After 1 h, 4-methoxyacetophenone (0.6 g, 4.0 mmol) was added in one portion and the reaction heated to 90° C. A second portion of sodium hydride (0.15 g, 60% suspension in oil, 0.4 mmol) was added and the exothermic reaction turns deep red. After 20 min, the reaction was cooled to 25° C. diluted with water (20 mL), extracted with EtOAc (10 mL) and the aqueous phase separated. The aqueous phase was acidified with 2 N HCl to pH 2 and the crude product collected. Recrystalization with ethanol gave the desired product as a yellow solid (0.4 g, 30%). mp 174-175° C.; CIMS m/e calc'd for C 19 H 16 NO 5 : 338.1028, found 338.1022; Analysis calc'd for C 19 H 15 NO 5 : C, 67.65; H, 4.48; N, 4.15; found: C, 67.87; H, 4.29; N, 3.99.

Step 3. Synthesis of 12 from 11.

A solution of 11 (0.2 g, 0.6 mmol) in EtOH (5 mL) was treated with hydrazine hydrate (0.1 mL, 1.8 mmol) and p-TsOH (3 mg). The reaction was heated to reflux and stirred for 2 h. The reaction was cooled to 25° C. and the product collected as a yellow solid (0.1 g, 50%). mp 268° C.; CIMS m/e calc'd for C 19 H 16 N 3 O 3 : 334.1192, found: 334.1168; Analysis calc'd for C 19 H 15 N 3 O 3 : C, 68.46; H, 4.54; N, 12.61; found: C, 68.81; H, 4.39; N, 12.45.

Example II

Preparation of 3-(4-methoxyphenyl)-5-(chloroacetamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 13 from 12.

A suspension of 12 (1.0 g, 3.0 mmol) in MeOH (10 mL) was treated with conc. HCl (1 mL) and heated to reflux. After 2 h, the reaction was cooled and the product was collected as a greenish solid (0.7 g, 81%). mp 273° C.; CIMS m/e calc'd for C 17 H 13 N 3 O 2 :292.1086, found: 292.1080; Analysis calc'd for C 17 H 14 N 3 O 2 : C, 69.85; H, 4.83; N, 14.37; found: C, 69.99; H, 4.59; N, 14.44.

Step 2. Synthesis of 14 from 13.

A suspension of 13 (20 mg, 0.07 mmol) in dioxane (2 mL) was treated with aqueous sat. NaHCO 3 (1 mL) and chloroacetyl chloride (30 mL, 0.21 mmol). The reaction was heated to 50° C. and stirred for 2 h. The reaction was cooled, poured into water (2 mL), extracted with EtOAc (10 mL), the organic layer separated, dried (MgSO 4 ) and the solvent removed at reduced pressure. The solid residue was recrystallized from EtOH to give the product as a yellow solid (9 mg, 35%). mp 274° C.; CIMS m/e calc'd for C 19 H 15 N 3 O 3 Cl: 368.0802, found: 368.0818.

Example III

Preparation of 3-(4-methoxyphenyl)-5-(cyclopropylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using cyclopropylacetyl chloride as the starting material. mp 289° C.; CIMS m/e calc'd for C 21 H 18 N 3 O 3 : 360.1348, found: 360.1330.

Example IV

Preparation of 3-(4-methoxyphenyl)-5-(isopropylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using isopropylacetyl chloride as the starting material. mp 288° C.; CIMS m/e calc'd for C 21 H 20 N 3 O 3 : 362.1505, found: 362.1535.

Example V

Preparation of 3-(4-methoxyphenyl)-5-(ethylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using propionyl chloride as the starting material. mp 287 ° C.; CIMS m/e calc'd for C 20 H 18 N 3 O 3 : 348.1348, found: 348.1313.

Example VI

Preparation of 3-(4-methoxyphenyl)-5-(cyclopentylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using cyclopentylacetyl chloride as the starting material. mp 267° C.; CIMS m/e calc'd for C 23 H 22 N 3 O 3 : 388.1661, found: 388.1626.

Example VII

Preparation of 3-(4-methoxyphenyl)-5-(cyclobutylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using cyclobutylacetyl chloride as the starting material. mp 297° C.; CIMS m/e calc'd for C 22 H 20 N 3 O 3 : 374.1505, found: 374.1530.

Example VIII

Preparation of 3-(4-methoxyphenyl)-5-(phenylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using phenylacetyl chloride as the starting material. mp 280° C.; CIMS m/e calc'd for C 25 H 20 N 3 O 3 : 410.1505, found: 410.1533.

Example IX

Preparation of 3-(4-methoxyphenyl)-5-(butylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using butyryl chloride as the starting material. mp 282° C.; CIMS m/e calc'd for C 21 H 20 N 3 O 3 : 362.1505, found: 362.1500.

Example X

Preparation of 3-(4-methoxyphenyl)-5-((4-chlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using 4-chlorophenylacetyl chloride as the starting material. mp 238° C.; CIMS m/e calc'd for C 25 H 19 N 3 O 3 Cl: 444.1115, found: 444.1110.

Example XI

Preparation of 3-(4-methoxyphenyl)-5-((3-methoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using 3-methoxyphenylacetyl chloride as the starting material. mp >300° C.; CIMS m/e calc'd for C 26 H 22 N 3 O 4 : 440.1610, found: 440.1620.

Example XII

Preparation of 3-(4-methoxyphenyl)-5-((4-methoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using 4-methoxyphenylacetyl chloride as the starting material. mp 280° C.; CIMS m/e calc'd for C 26 H 22 N 3 O 4 : 440.1610, found: 440.1630.

Example XIII

Preparation of 3-(4-methoxyphenyl)-5-((3,4-dimethoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using 3,4-dimethoxyphenylacetyl chloride as the starting material. mp >300° C.; CIMS m/e calc'd for C 27 H 24 N 3 O 5 : 470.1716, found: 470.1731.

Example XIV

Preparation of 3-(4-methoxyphenyl)-5-((2,5-dimethoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using 2,5-dimethoxyphenylacetyl chloride as the starting material. mp 226° C.; CIMS m/e calc'd for C 27 H 24 N 3 O 5 : 470.1716, found: 470.1739.

Example XV

Preparation of 3-(2-methoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 2-methoxyacetophenone as the starting material. mp 276° C.; CIMS m/e calc'd for C 19 H 16 N 3 O 3 : 334.1192, found: 334.1169.

Example XVI

Preparation of 3-(3,4-dimethoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 3,4-dimethoxyacetophenone as the starting material. mp >300° C.; CIMS m/e calc'd for C 20 H 18 N 3 O 4 : 364.1297, found: 364.1288.

Example XVII

Preparation of 3-(4-methoxyphenyl)-5-((3,4-ethylenedioxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 15 from 11.

A suspension of 11 (5 g, 14.8 mmol) in MeOH (50 mL) was treated with conc. HCl (3 mL) and heated to reflux. After stirring for 2 h, the reaction was cooled to 0° C. and the product collected as a yellow solid (4.2 g, 96%). mp 173° C.; CIMS m/e calc'd for C 17 H 14 NO 4 : 296.0923, Found: 296.0901.

Step 2. Synthesis of 16 from 15.

A suspension of 15 (20 mg, 0.07 mmol) in acetone (2 mL) was treated with NaHCO 3 (10 mg) and the acid chloride of (3,4-methylenedioxyphenyl)acetic acid (prepared by heating the acid in a benzene:thionyl chloride 4:1 mixture at 50° C. for 2 h, removing the volatile components at reduced pressure, and using the crude acid chloride without further purification). The reaction was heated to 50° C. and stirred for 2 h. The reaction was cooled, poured into water (4 mL), extracted with EtOAc (10 mL), dried (MgSO 4 ), filtered and concentrated. The crude triketone was suspended in EtOH (2 mL), treated with hydrazine hydrate (0.05 mL) and p-TsOH (1 mg) and heated to reflux for 2 h. The reaction was cooled to 0° C. and the product filtered to give a yellow solid (6.5 mg, 20%). mp 297° C.; CIMS m/e calc'd for C 26 H 20 N 3 O 5 : 454.1403, Found: 454.1398.

Example XVIII

Preparation of 3-(4-dimethoxyphenyl)-5-((3-thiophene)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XVII using the acid chloride of 3-thiopheneacetic acid as the starting material. mp 293° C.; CIMS m/e calc'd for C 23 H 18 N 3 O 3 S: 416.1069, found: 416.1088.

Example XIX

Preparation of 3-(4-methoxyphenyl)-5-((2-methoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XVII using the acid chloride of 2-methoxyphenylacetic acid as the starting material. mp 255° C.; CIMS m/e calc'd for C 26 H 22 N 3 O 4 : 440.1610, found: 440.1622.

Example XX

Preparation of 3-(4-methoxyphenyl)-5-((3,4-dichlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XVII using the acid chloride of 3,4-dichlorophenylacetic acid as the starting material. mp 299° C.; CIMS m/e calc'd for C 25 H 18 N 3 O 3 Cl 2 : 478.0725, found: 478.0744.

Example XXI

Preparation of 3-(4-methoxyphenyl)-5-((2,4-dichlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XVII using the acid chloride of 2,4-dichlorophenylacetic acid as the starting material. mp 286° C.; CIMS m/e calc'd for C 25 H 18 N 3 O 3 Cl 2 : 478.0725, found: 478.0734.

Example XXII

Preparation of 3-(4-methoxyphenyl)-5-((2-chlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XVII using the acid chloride of 2-chlorophenylacetic acid as the starting material. mp 300° C.; CIMS m/e calc'd for C 25 H 19 N 3 O 3 Cl: 444.1115, found: 444.1111.

Example XXIII

Preparation of 3-(4-methoxyphenyl)-5-(aminoacetamido)indeno[1,2-c]pyrazol-4-one

A suspension of 14 (15 mg, 0.04 mmol) in EtOH (1 mL) was treated with conc. NH 4 OH (1 mL), placed in a sealed tube and heated to 80° C. for 3 h. The reaction was cooled and the solvent removed at reduced pressure. The residue was recrystallized from EtOH to give the product as a yellow solid (9 mg, 62%). mp >300° C.; CIMS m/e calc'd for C 20 H 19 N 4 O 3 : 363.1457, Found: 363.1431.

Example XXIV

Preparation of 3-(4-methoxyphenyl)-5-((2-hydroxyethyl)aminoacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using hydroxylamine as the starting material. mp 243° C.; CIMS m/e calc'd for C 21 H 21 N 4 O 4 : 393.1563, found: 393.1539.

Example XXV

Preparation of 3-(4-methoxyphenyl)-5-(N,N-dimethylaminoacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using dimethylamine as the starting material. mp 279° C.; CIMS m/e calc'd for C 21 H 21 N 4 O 3 : 377.1614, found: 377.1640.

Example XXVI

Preparation of 3-(4-methoxyphenyl)-5-(piperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using piperazine as the starting material. mp 277° C.; CIMS m/e calc'd for C 23 H 24 N 5 O 3 : 418.1879, found: 418.1899.

Example XXVII

Preparation of 3-(4-methoxyphenyl)-5-(4-methylpiperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-methylpiperizine as the starting material. mp >300° C.; CIMS m/e calc'd for C 24 H 26 N 5 O 3 : 432.2036, found: 432.2030.

Example XXVIII

Preparation of 3-(4-methoxyphenyl)-5-(4-(2-hydroxyethyl)piperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-hydroxyethylpiperizine as the starting material. mp >300° C.; CIMS m/e calc'd for C 25 H 28 N 5 O 4 : 462.2141, found: 462.2128.

Example XXIX

Preparation of 3-(4-methoxyphenyl)-5-(piperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using piperidine as the starting material. mp 291° C.; CIMS m/e calc'd for C 24 H 25 N 4 O 3 : 417.1927, found: 417.1955.

Example XXX

Preparation of 3-(4-methoxyphenyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-aminomethylpiperidine as the starting material. mp >300° C.; CIMS m/e calc'd for C 25 H 28 N 5 O 3 : 446.2192, found: 446.2166.

Example XXXI

Preparation of 3-(4-methoxyphenyl)-5-(ethylaminoacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using ethylamine as the starting material. mp 250° C.; CIMS m/e calc'd for C 21 H 21 N 4 O 3 : 377.1614, found: 377.1644.

Example XXXII

Preparation of 3-(4-methoxyphenyl)-5-(thiomorpholinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using thiomorpholine as the starting material. mp 298° C.; CIMS m/e calc'd for C 23 H 23 N 4 O 3 S: 435.1491, found: 435.1477.

Example XXXIII

Preparation of 3-(4-methoxyphenyl)-5-(morpholinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using morpholine as the starting material. mp 295° C.; CIMS m/e calc'd for C 23 H 23 N 4 O 4 : 419.1719, found: 419.1744.

Example XXXIV

Preparation of 3-(4-methoxyphenyl)-5-(pyrrolidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using pyyrolidine as the starting material. mp 279° C.; CIMS m/e calc'd for C 23 H 23 N 4 O 3 : 403.1770, found: 403.1761.

Example XXXV

Preparation of 3-(4-methoxyphenyl)-5-(4-pyridinylaminomethylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-aminomethylpyridine as the starting material. mp >300° C.; CIMS m/e calc'd for C 25 H 22 N 5 O 3 : 440.1723, found: 440.1762.

Example XXXVI

Preparation of 3-(4-methoxyphenyl)-5-((4-acetamidophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

A suspension of 18 (10 mg, 0.02 mmol) in dioxane (1 mL) was treated with aqueous sat. NaHCO 3 (0.5 mL) and acetyl chloride (0.01 mL) and heated at 50° C. for 1 h. The reaction was cooled, poured into water (5 mL), extracted with EtOAc (10 mL), the organic layer separated, dried (MgSO 4 ) and the solvent removed at reduced pressure. The residue was recrystallized from EtOH to give the product as a yellow solid (5.6 mg, 61%). mp 268° C.; CIMS m/e calc'd for C 27 H 23 N 4 O 4 : 467.1719, Found: 467.1730.

Example XXXVII

Preparation of 3-(4-methoxyphenyl)-5-((4-methoxycarbonylaminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXXII using methylchloroformate as the starting material. mp 257° C.; CIMS m/e calc'd for C 27 H 23 N 4 O 5 : 483.1668, found: 483.1633.

Example XXXVIII

Preparation of 3-(4-methoxyphenyl)-5-((4-aminomethylcarbonylaminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII and XXXII using chloroacetyl chloride and conc. NH 4 OH as the starting materias. mp 228° C.; CIMS m/e calc'd for C 27 H 24 N 5 O 4 : 482.1828, found: 482.1844.

Example XXXIX

Preparation of 3-(4-methoxyphenyl)-5-((4-N,N-dimethylaminomethylcarbonylaminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII and XXXII using chloroacetyl chloride and dimethyl amine as the starting materias. mp >300° C.; CIMS m/e calc'd for C 29 H 28 N 5 O 4 : 510.2141, found: 510.2121.

Example XL

Preparation of 3-(4-methoxyphenyl)-5-((4-azidophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

A solution of example XXXVI (20 mg, 0.04 mmol) in DMF (2 mL) was treated with 5% palladium on carbon (5 mg) and hydrogentaed at atmospheric pressure using a hydrogen baloon. After 2 h, the solution was filtered (Celite), and the solvent removed at reduced pressure. The residue was recrystallized from EtOH to give the product as a yellow solid (15 mg, 78%). mp >300° C.; CIMS m/e calc'd for C 25 H 19 N 6 O 3 : 451.1519, found: 451.1544.

Example XLI

Preparation of 3-(4-methoxyphenyl)-5-((4-aminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXVII using the acid chloride of 4-azidophenylacetic acid as the starting material. mp 283° C.; CIMS m/e calc'd for C 25 H 21 N 4 O 3 : 425.1614, found: 425.1643.

Example XLII

Preparation of 3-(4-methoxyphenyl)-5-(phenylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 20 from 15.

A suspension of 15 (0.5 g, 1.7 mmol) in acetone (10 mL) was treated with NaHCO 3 (0.5 g) and phenyl chloroformate. The mixture was heated to 50° C. for 2 h. The reaction was cooled, poured into water (20 mL), extracted with EtOAc (40 mL), the organic layer separated, dried (MgSO 4 ) and the solvent removed at reduced pressure. The residue was suspended in EtOH (10 mL) and treated with hydrazine hydrate (0.16 mL, 5.1 mmol) and p-TsOH (10 mg). The mixture was heated to reflux and stirred for 3 h. The reaction was cooled to 0° C. and the product collected as a yellow solid (0.25 g, 36%). mp 195° C.; CIMS m/e calc'd for C 24 H 18 N 3 O 4 : 412.1297, Found: 412.1308.

Step 2. Synthesis of 21 from 20.

A solution of 20 (20 mg, 0.05 mmol) in DMSO (2 mL) was treated with aniline (20 mL, mmol) and dimethylaminopyridine (1 mg). The mixture was heated to 80° C. for 2 h. The reaction was cooled, poured into water (4 mL), extracted with EtOAc (15 mL), the organic layer separated, dried (MgSO 4 ) and the solvent removed at reduced pressure. The residue was recrystallized from EtOH to give the product as a yellow solid (9 mg, 44%). mp >300° C.; CIMS m/e calc'd for C 24 H 19 N 4 O 3 : 411.1457, Found: 411.1432.

Example XLIII

Preparation of 3-(4-methoxyphenyl)-5-(butylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using butyl amine as the starting material. mp 252° C.; CIMS m/e calc'd for C 21 H 21 N 4 O 3 : 377.1614, found: 377.1633.

Example XLIV

Preparation of 3-(4-methoxyphenyl)-5-(4-aminobenzylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using 4-aminobenzyl amine as the starting material. mp >300° C.; CIMS m/e calc'd for C 25 H 22 N 5 O 3 : 440.1723, found: 440.1700.

Example XLV

Preparation of 3-(4-methoxyphenyl)-5-(4-pyridylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using 4-aminomethylpyridine as the starting material. mp >300° C.; CIMS m/e calc'd for C 24 H 20 N 5 O 3 : 426.1566, found: 426.1533.

Example XLVI

Preparation of 3-(4-hydroxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

A suspension of 12 (20 mg, 0.07 mmol) in CH 2 Cl 2 (2 mL) was treated with excess BBr 3 (1.0 mL, 1.0 M in CH 2 Cl 2 ) and stirred for 20 h. The reaction was slowly poured into aqueous sat. NaHCO 3 (5 mL), extracted with EtOAc (10 mL), dried (MgSO 4 ) and concentrated. The residue was recrystallized from EtOH to give the desired product as a yellow solid (7.5 mg, 33%). mp >300° C.; CIMS m/e calc'd for C 18 H 14 N 3 O 3 : 320.1035, Found: 320.1050.

Example XLVII

Preparation of 3-(4-methoxyphenyl)-5-(formamido)indeno[1,2-c]pyrazol-4-one

A suspension of 13 (20 mg, 0.06 mmol) in formic acid (2 mL) was heated to 100° C. for 2 h. The reaction mixture was cooled and the solvent removed at reduced pressure. The residue was recrystallized from EtOH to give the desired product as a yellow solid (12 mg, 63%). mp 280° C.; CIMS m/e calc'd for C 18 H 14 N 3 O 3 : 320.1035, Found: 320.1040.

Example XLVIII

Preparation of 3-(3-pyridyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 24 from 3-acetylpyridine.

A solution of 3-acetylpyridine (1.0 g, 8.3 mmol) in benzene (3 mL) was treated with 1,1-dimethylhydrazine (0.62 mL, 8.3 mmol) and p-TsOH (5 mg). The mixture was heated to 85° C. and stirred for 3 h. The reaction was cooled and the solvent removed at reduced pressure. This crude hydrazone was treated with 1.0 M NaN(TMS) 2 in THF (16.6 mL, 16.6 mmol) at 25° C. over 5 min. After 30 min dimethyl 3-acetamidophthalate (2.1 g, 8.3 mmol) was added in one portion and the reaction heated to reflux. Stirring was continued for 6 h. The reaction was cooled and quenched by the slow addition of TFA. The solvent was removed at reduced pressure and the residue chromatographed (silica, 2.5-5% MeOH/CH 2 Cl 2 ) to give the product as a yellow solid (0.35 g, 14%). mp 265° C.; CIMS m/e calc'd for C 17 H 13 N 2 O 4 : 309.0875, Found: 309.0888.

Step 2. Synthesis of 25 from 24.

A suspension of 24 (30 mg, 0.09 mmol) in EtOH (2 mL) was treated with hydrazine hydrate (0.05 mL) and p-TsOH (1 mg) and heated to reflux. After stirring for 2 h. the reaction was cooled and the product filtered to give a yellow solid (12 mg, 44%). mp >300° C.; CIMS m/e calc'd for C 17 H 13 N 4 O 2 : 305.1039, Found: 305.1048.

Example XLIX

Preparation of 3-(4-pyridyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLVIII using 4-acetylpyridine as the starting material. mp >300° C.; CIMS m/e calc'd for C 17 H 13 N 4 O 2 : 305.1039, found: 305.1046.

Example L

Preparation of 3-(4-pyridyl)-5-(formamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLVII using 4-acetylpyridine as the starting material. mp >300° C.; CIMS m/e calc'd for C 16 H 11 N 4 O 2 : 291.0882, found: 291.0882.

Example LI

Preparation of 3-phenyl-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using acetophenone as the starting material. mp >300° C.; CIMS m/e calc'd for C 18 H 13 N 3 O 2 : 304.1065, found: 304.1086.

Example LII

Preparation of 3-(4-methylthiophenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 4′-methylthioacetophenone as the starting material. mp 283° C.; CIMS m/e calc'd for C 19 H 15 N 3 O 2 S: 350.0956, found: 350.0963.

Example LIII

Preparation of 3-(4-methylsulphonylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared by oxidation of the product of example LII. mp >300° C.; CIMS m/e calc'd for C 19 H 15 N 3 O 4 S: 382.0860, found: 382.0862.

Example LIV

Preparation of 3-(4-N,N-dimethylaminophenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 4′-N,N,-dimethylaminoacetophenone as the starting material. mp >300° C.; CIMS m/e calc'd for C 20 H 18 N 4 O 2 : 347.1496, found: 347.1508.

Example LV

Preparation of 3-(4-N,N-dimethylaminophenyl)-5-(morpholinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LIV and morpholine as the starting materials. mp >300° C.; CIMS m/e calc'd for C 24 H 26 N 5 O 3 : 432.2036, found: 432.2020.

Example LVI

Preparation of 3-(4-N,N-dimethylaminophenyl)-5-(dimethylaminoacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LIV and dimethylamine as the starting materials. mp >300° C.; CIMS m/e calc'd for C 22 H 24 N 5 O 2 : 390.1930, found: 390.1948.

Example LVII

Preparation of 3-(4-(1-piperidinyl)phenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 4′-(1-piperidinyl)acetophenone as the starting material. mp 291° C.; CIMS m/e calc'd for C 23 H 22 N 4 O 2 : 387.1801, found: 387.1821.

Example LVIII

Preparation of 3-(4-morpholinyl)phenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 4′-morpholinylacetophenone as the starting material. mp >300° C.; CIMS m/e calc'd for C 22 H 20 N 4 O 3 : 388.1528, found: 388.1535.

Example LIX

Preparation of 3-(4-ethoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 4′-ethoxyacetophenone as the starting material. mp 288° C.; CIMS m/e calc'd for C 20 H 17 N 3 O 3 : 348.1325, found: 348.1348.

Example LX

Preparation of 3-(4-butylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 4′-butylacetophenone as the starting material. mp 259° C.; CIMS m/e calc'd for C 22 H 21 N 3 O 2 : 360.1701, found: 360.1712.

Example LXI

Preparation of 3-(4-ethylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 4′-ethylacetophenone as the starting material. mp 294° C.; CIMS m/e calc'd for C 20 H 17 N 3 O 2 : 331.1310, found: 331.1321.

Example LXII

Preparation of 3-(4-n-propylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 4′-n-propylacetophenone as the starting material. mp 269° C.; CIMS m/e calc'd for C 21 H 19 N 3 O 2 : 346.1555, found: 346.1554.

Example LXIII

Preparation of 3-(4-methoxyphenyl)-5-carbamoylaminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using concentrated ammonium hydroxide as the starting material. mp >300° C.; CIMS m/e calc'd for C 18 H 15 N 4 O 3 : 335.1144, found: 335.1113.

Example LXIV

Preparation of 3-(4-methoxyphenyl)-5-(dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using dimethylamino hydrazine as the starting material. mp >300° C.; CIMS m/e calc'd for C 20 H 20 N 5 O 3 : 378.1566, found: 378.1555.

Example LXV

Preparation of 3-(4-methoxyphenyl)-5-(methylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using methylamine as the starting material. mp >300° C.; CIMS m/e calc'd for C 19 H 17 N 4 O 3 : 349.1300, found: 349.1311.

Example LXVI

Preparation of 3-(4-methoxyphenyl)-5-(morpholinocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using N-aminomorpholine as the starting material. mp >300° C.; CIMS m/e calc'd for C 22 H 22 N 5 O 4 : 420.1671, found: 420.1655.

Example LXVII

Preparation of 3-(4-methoxyphenyl)-5-(cis-2-aminocyclohexanylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using cis-1,2-diaminocyclohexane as the starting material. mp >300° C.; CIMS m/e calc'd for C 24 H 26 N 5 O 3 : 432.2035, found: 432.2020.

Example LXVIII

Preparation of 3-(4-methoxyphenyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using (4-amino)methylpiperazine as the starting material. mp >300° C.; CIMS m/e calc'd for C 23 H 25 N 6 O 3 : 433.1987, found: 433.1999.

Example LXIX

Preparation of 3-(4-methoxyphenyl)-5-(4-uridomethylpiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using example XXX as the starting material. mp >300° C.; CIMS m/e calc'd for C 26 H 29 N 6 O 4 : 489.2250, found: 489.2209.

Example LXX

Preparation of 3-(4-methoxyphenyl)-5-(4-(2-pyridyl)piperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-(2-pyridyl)piperazine as the starting material. mp >300° C.; CIMS m/e calc'd for C 28 H 27 N 6 O 3 : 495.2144, found: 495.2111.

Example LXXI

Preparation of 3-(4-methoxyphenyl)-5-(4-(aminoethyl)piperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-(aminoethyl)piperazine as the starting material. mp >300° C.; CIMS m/e calc'd for C 25 H 29 N 6 O 3 : 461.2300, found: 461.2333.

Example LXXII

Preparation of 3-(4-methoxyphenyl)-5-(4-amidopiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using isonipecotamide as the starting material. mp >300° C.; CIMS m/e calc'd for C 25 H 26 N 5 O 4 : 460.1984, found: 460.1998.

Example LXXIII

Preparation of 3-(4-methoxyphenyl)-5-(4-hydroxypiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-hydroxypiperadine as the starting material. mp >300° C.; CIMS m/e calc'd for C 24 H 25 N 4 O 4 : 433.1875, found: 433.1844.

Example LXXIV

Preparation of 3-(4-methoxyphenyl)-5-(4-hydroxmethylypiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-hydroxmethylypiperadine as the starting material. mp >300° C.; CIMS m/e calc'd for C 25 H 27 N 4 O 4 : 447.2032, found: 447.2002.

Example LXXV

Preparation of 3-(4-methoxyphenyl)-5-(4-amidopiperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-amidopiperazine as the starting material. mp >300° C.; CIMS m/e calc'd for C 24 H 25 N 6 O 6 : 493.1835, found: 493.1802.

Example LXXVI

Preparation of 3-(4-methoxyphenyl)-5-(4-dimethylaminopiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-dimethylaminopiperadine as the starting material. mp >300° C.; CIMS m/e calc'd for C 26 H 30 N 5 O 5 : 492.2246, found: 492.2220.

Example LXXVII

Preparation of 3-(4-methoxyphenyl)-5-(4-aminopiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-aminopiperadine as the starting material. mp >300° C.; CIMS m/e calc'd for C 24 H 26 N 5 O 5 : 464.1933, found: 464.1975.

Example LXXVIII

Preparation of 3-(4-(dimethylamino)phenyl)-5-((4-methyl-1-piperazinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LIV and 1-methylpiperazine as the starting materials. mp >300° C.; ESI-MS m/e calc'd for C 25 H 29 N 6 O 2 : 445.2352, found: 445.2359.

Example LXXIX

Preparation of 3-(4-(dimethylamino)phenyl)-5-((4-amino methyl-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LIV and 4-(aminomethyl)piperidine as the starting materials. ESI-MS m/e calc'd for C 26 H 31 N 6 O 2 : 459.2508, found: 459.2508.

Example LXXX

Preparation of 3-(4-(dimethylamino)phenyl)-5-((4-hydroxy-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LIV and 4-hydroxypiperidine as the starting materials. mp 267° C.; ESI-MS m/e calc'd for C 25 H 28 N 5 O 3 : 446.2192, found: 446.2206.

Example LXXXI

Preparation of 3-(4-(4-morpholinyl)phenyl)-5-(4-morpholinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LVIII and morpholine as the starting materials. mp 258° C.; ESI-MS m/e calc'd for C 26 H 28 N 5 O 4 : 474.2141, found: 474.2151.

Example LXXXII

Preparation of 3-(4-(4-morpholinyl)phenyl)-5-((4-methyl-1-piperazinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LVIII and 1-methylpiperazine as the starting materials. mp 258° C.; ESI-MS m/e calc'd for C 27 H 31 N 6 O 3 : 487.2457, found: 487.2447.

Example LXXXIII

Preparation of 3-(4-(4-morpholinyl)phenyl)-5-((4-hydroxy-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LVIII and 4-hydroxypiperidine as the starting materials. mp 245° C.; ESI-MS m/e calc'd for C 27 H 30 N 5 O 4 : 488.2298, found: 488.2290.

Example LXXXIV

Preparation of 3-(4-(4-morpholinyl)phenyl)-5-((4-amino methyl-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LVIII and 4-(aminomethyl)piperidine as the starting materials. mp 240° C.; ESI-MS m/e calc'd for C 28 H 33 N 6 O 3 : 501.2614, found: 501.2619.

Example LXXXV

Preparation of 3-(4-(dimethylamino)phenyl)-5-((((4-methyl-1-piperazinyl)amino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples I, XXVII, and XLII employing the 4-(dimethylamino) acetophenone and 1-amino-4-methylpiperazine as the starting materials. mp >300° C.; ESI-MS m/e calc'd for C 24 H 28 N 7 O 2 : 446.2304, found: 446.2310.

Example LXXXVI

Preparation of 3-(i-propyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 26 from 3-nitrophthalic Anhydride.

A solution of 3-nitrophthalic anhydride (9.7 g, 50 mmol) and 1,1,1-trifluoro-5-methyl-2,4-hexanedione (9.1 g, 50 mmol) in acetic anhydride (28.3 mL, 300 mmol) was treated with triethylamine (13.95 mL, 100 mmol) and stirred at 25° C. for 4 h. The solution was diluted with 1 N HCl (200 mL) and the precipate collected and washed with water (200 mL) and hexane (400 mL) to give the product as a yellow solid (11.1 g, 85%). mp 127-129° C.; CIMS (M+H) calc'd for C 13 H 12 NO 5 : 262.0715, found: 262.0694.

Step 2. Synthesis of triketone 27 from 26.

A solution of 26 (11 g, 42 mmol) in EtOH (224 mL) and water (56 mL) was treated with zinc (90 g, 1.4 mol) and calcium chloride (3 g, 27 mmol) and heated to reflux for 16 h. The reaction was filtered (Celite) and the filtrate was concentrated at reduced pressure to give an aqueous residue which was extracted with EtOAc (100 mL). The organic layer was separated and washed with sat. EDTA (100 ml) and brine (100 mL), dried (MgSO 4 ), filtered, and concentrated at reduced pressure to give a yellow solid. Trituration with hexane gave the product as a yellow solid (7.1 g, 73%). mp 241-243° C.; CIMS (M+H) calc'd for C 13 H 14 NO 3 : 232.0974, found: 232.0962.

Step 3. Synthesis of 28 from 27.

A solution of 27 (500 mg, 2.16 mmol) in CH2Cl2 (5 mL) was treated with Et3N (0.36 mL, 2.59 mmol) and stirred at 25° C. for 15 min. The reaction mixture was treated with acetyl chloride (0.18 mL, 2.38 mmol) and stirred at 25° C. for 1 h. The reaction mixture was quenched with 1 N HCl (20 mL) and extracted with EtOAc (20 mL). The organic layer was separated, dried (MgSO4), filtered, and concentrated at reduced pressure to give a brown residue. Trituration with hexane gave the product as a tan solid (484 mg, 82%). mp 241-243° C.; CIMS (M+H) calc'd for C 15 H 16 NO 4 : 274.1079, found: 274.1093.

Step 4. Synthesis of 29 from 28.

A solution of 28 (240 mg, 0.88 mmol) in BuOH (5 mL) was treated with hydrazine hydrate (0.055 mL, 1.76 mmol) and p-TsOH (8.4 mg, 0.044 mmol). The reaction was heated to reflux and stirred for 4 h. The reaction was cooled to 25° C. and the solvent removed at reduced pressure. Recrystalization with i-propyl alcohol gave the product collected as an off-white solid (173 mg, 73%). mp >250° C.; ESIMS (M+H) calc'd for C 15 H 16 N 3 O 2 : 270.1242, found: 270.1258.

Example LXXXVII

Preparation of 3-(c-propyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using the c-propyl analog of 26 as the starting material. mp 220-221° C.; CIMS (M+H) calc'd for C 15 H 14 N 3 O 2 : 268.1086, found: 268.1078.

Example LXXXVIII

Preparation of 3-(t-butyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using the t-butyl analog of 26 as the starting material. mp >250° C.; CIMS (M+H) calc'd for C 16 H 18 N 3 O 2 : 284.1399, found: 284.1395.

Example LXXXIX

Preparation of 3-(2-thienyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using the 2-thienyl analog of 26 as the starting material. mp 269° C.; CIMS (M+H) calc'd for C 16 H 12 N 3 O 2 S: 310.0650, found: 310.0635.

Example XC

Preparation of 3-(3-methyl-2-thienyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using the 3-methyl-2-thienyl analog of 26 as the starting material. mp 275° C.; ESIMS (M+H) calc'd for C 17 H 14 N 3 O 2 S: 324.0811, found: 324.0807.

Example XCI

Preparation of 3-(ethyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the ethyl analog of 15 as the starting materials. mp >250° C.; CIMS (M+H) calc'd for C 13 H 13 N 4 O 2 : 257.1039, found: 257.1033.

Example XCII

Preparation of 3-(n-propyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the n-propyl analog of 15 as the starting materials. mp 187-189° C.; CIMS (M+H) calc'd for C 14 H 15 N 4 O 2 : 271.1195, found: 271.1187.

Example XCIII

Preparation of 3-(i-propyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the i-propyl analog of 15 as the starting materials. mp >250° C.; CIMS (M+H) calc'd for C 14 H 15 N 4 O 2 : 271.1195, found: 271.1196.

Example XCIV

Preparation of 3-(c-propyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the c-propyl analog of 15 as the starting materials. mp 252-253° C.; ESIMS (M-H) calc'd for C 14 H 11 N 4 O 2 : 267.0881, found: 267.0884.

Example XCV

Preparation of 3-(c-hexyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the c-hexyl analog of 15 as the starting materials. mp 178-179° C.; ESIMS (M+H) calc'd for C 17 H 19 N 4 O 2 : 311.1507, found: 311.1500.

Example XCVI

Preparation of 3-(2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 2-thienyl analog of 15 as the starting materials. mp 214° C.; CIMS m+ calc'd for C 15 H 10 N 4 O 2 S: 310.0517, found: 310.0524.

Example XCVII

Preparation of 3-(3-methyl-2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 3-methyl-2-thienyl analog of 15 as the starting materials. mp 270° C.; ESIMS (M+H) calc'd for C 16 H 13 N 4 O 2 S: 325.0759, found: 325.0744.

Example XCVIII

Preparation of 3-(5-methyl-2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 5-methyl-2-thienyl analog of 15 as the starting materials. mp >280° C.; ESIMS (M+H) calc'd for C 16 H 13 N 4 O 2 S: 325.0759, found: 325.0761.

Example XCIX

Preparation of 3-(5-ethylcarboxyl-2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 5-ethylcarboxyl-2-thienyl analog of 15 as the starting materials. mp >280° C.; ESIMS (M+H) calc'd for C 18 H 15 N 4 O 4 S: 383.0813, found: 383.0788.

Example C

Preparation of 3-(3-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 3-thienyl analog of 15 as the starting materials. mp >280° C.; ESIMS (M+H) calc'd for C 15 H 11 N 4 O 2 S: 311.0603, found: 311.0594.

Example CI

Preparation of 3-(5-chloro-3-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 5-chloro-3-thienyl analog of 15 as the starting materials. mp >300° C.; ESIMS (M+H) calc'd for C 15 H 10 N 4 O 2 SCl: 345.0209, found: 345.0213.

Example CII

Preparation of 3-(2,5-dimethyl-3-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 2,5-dimethyl-3-thienyl analog of 15 as the starting materials. mp >280° C.; ESIMS (M+H) calc'd for C 17 H 15 N 4 O 2 S: 339.0916, found: 339.0905.

Example CIII

Preparation of 3-(2-furanyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 2-furanyl analog of 15 as the starting materials. mp 278° C.; ESIMS (M+H) calc'd for C 15 H 11 N 4 O 3 : 295.0831, found: 295.0838.

Example CIV

Preparation of 3-(i-propyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the i-propyl analog of 15 as the starting materials. mp 231-233° C.; ESIMS (M+H) calc'd for C 16 H 20 N 5 O 2 : 314.1616, found: 314.1599.

Example CV

Preparation of 3-(c-propyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the c-propyl analog of 15 as the starting materials. mp XXX ° C.; ESIMS (M+H) calc'd for C 16 H 18 N 5 O 2 : 312.1460, found: 312.1487.

Example CVI

Preparation of 3-(c-hexyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the c-hexyl analog of 15 as the starting materials. mp 229-231° C.; ESIMS (M+H) calc'd for C 19 H 24 N 5 O 2 : 354.1929, found: 354.1932.

Example CVII

Preparation of 3-(2-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the 2-thienyl analog of 15 as the starting materials. mp 279° C.; ESIMS (M+H) calc'd for C 17 H 16 N 5 O 2 S: 354.1024, found: 354.1025.

Example CVIII

Preparation of 3-(5-methoxy-2-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,l-dimethylhydrazine and the 5-methoxy-2-thienyl analog of 15 as the starting materials. mp 280° C.; ESIMS (M+H) calc'd for C 18 H 18 N 5 O 3 S: 384.1130, found: 384.1119.

Example CIX

Preparation of 3-(5-methyl-2-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the 5-methyl-2-thienyl analog of 15 as the starting materials. mp >280° C.; ESIMS (M+H) calc'd for C 18 H 18 N 5 O 2 S: 368.1181, found: 368.1171.

Example CX

Preparation of 3-(5-ethylcarboxyl-2-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 11-dimethylhydrazine and the 5-ethylcarboxyl-2-thienyl analog of 15 as the starting materials. mp 252° C.; ESIMS (M+H) calc'd for C 20 H 20 N 5 O 4 S: 426.1236, found: 426.1251.

Example CXI

Preparation of 3-(3-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the 3-thienyl analog of 15 as the starting materials. mp 202° C.; ESIMS (M+H) calc'd for C 17 H 16 N 5 O 2 S: 354.1025, found: 354.1031.

Example CXII

Preparation of 3-(1-methyl-3-pyrrolyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 1-methyl-3-pyrrolyl analog of 15 as the starting materials. mp >300° C.; ESIMS (M+H) calc'd for C 16 H 14 N 5 O 2 : 308.1147, found: 308.1166.

Example CXIII

Preparation of 3-(2,5-dimethyl-3-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the 2,5-dimethyl-3-thienyl analog of 15 as the starting materials. mp 252° C.; ESIMS (M+H) calc'd for C 19 H 20 N 5 O 2 S: 382.1338, found: 382.1357.

Example CXIV

Preparation of 3-(2-furanyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the 2-furanyl analog of 15 as the starting materials. mp 202° C.; ESIMS (M+H) calc'd for C 17 H 16 N 5 O 3 : 338.1253, found: 338.1248.

Example CXV

Preparation of 3-(i-propyl)-5-(4-carbamoylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using isonipecotamide and the i-propyl analog of 14 as the starting materials. mp 224-225° C.; ESIMS (M+H) calc'd for C 21 H 26 N 5 O 3 : 396.2035, found: 396.2036.

Example CXVI

Preparation of 3-(c-hexyl)-5-(4-carbamoylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using isonipecotamide and the c-hexyl analog of 14 as the starting materials. mp 228-229° C.; ESIMS (M+H) calc'd for C 24 H 30 N 5 O 3 : 436.2348, found: 436.2345.

Example CXVII

Preparation of 3-(ethyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-(aminomethyl)piperidine and the ethyl analog of 14 as the starting materials. mp 174-176° C.; ESIMS (M+H) calc'd for C 20 H 26 N 5 O 2 : 368.2086, found: 368.2078.

Example CXVIII

Preparation of 3-(i-propyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-(aminomethyl)piperidine and the i-propyl analog of 14 as the starting materials. mp 218-220° C.; ESIMS (M+H) calc'd for C 21 H 28 N 5 O 2 : 382.2242, found: 382.2227.

Example CXIX

Preparation of 3-(c-propyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-(aminomethyl)piperidine and the c-propyl analog of 14 as the starting materials. mp 138-140° C.; ESIMS (M+H) calc'd for C 21 H 26 N 5 O 2 : 380.2086, found: 380.2079.

Example CXX

Preparation of 3-(c-hexyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-(aminomethyl)piperidine and the c-hexyl analog of 14 as the starting materials. mp 196-198° C.; ESIMS (M+H) calc'd for C 24 H 32 N 5 O 2 : 422.2555, found: 422.2540.

Example CXXI

Preparation of 3-(i-propyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1-amino-4-methylpiperazine and the i-propyl analog of 15 as the starting materials. mp 231-233° C.; ESIMS (M+H) calc'd for C 19 H 25 N 6 O 2 : 369.2038, found: 369.2039.

Example CXXII

Preparation of 3-(5-ethylcarboxyl-2-thienyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1-amino-4-methylpiperazine and the 5-ethylcarboxyl-2-thienyl analog of 15 as the starting materials. mp 249° C.; ESIMS (M+H) calc'd for C 23 H 25 N 6 O 4 S: 481.1657, found: 481.1642.

Example CXXIII

Preparation of 3-(5-carboxyl-2-thienyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

A solution of CXXII (30 mg, 0.05 mmol) in 3:1 THF/water (2 mL) was treated with LiOH (23 mg, 0.5 mmol) and the reaction was stirred at 25° C. for 12 h and then heated to reflux for 1 h. The organic solvent was removed at reduced pressure and the residue was partioned between EtOAc (5 mL) and water (5 mL). The organic layer was separated and the aqueous phase was adjusted to pH=2 with 1 M HCl and re-extracted with EtOAc (5 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated at reduced pressure to give a crude residue. Purification by reverse phase HPLC gave the product as a yellow solid (10.4 mg, 46%). mp 270° C.; ESIMS (M+H) calc'd for C 21 H 21 N 6 O 4 S: 453.1344, found: 453.1353.

Example CXXIV

Preparation of 3-(2,5-dimethyl-3-thienyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1-amino-4-methylpiperazine and the 2,5-dimethyl-3-thienyl analog of 15 as the starting materials. mp 250° C.; ESIMS (M+H) calc'd for C 22 H 25 N 6 O 2 S: 437.1760, found: 437.1771.

Example CXXV

Preparation of 3-(i-propyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 4-aminomorpholine and the i-propyl analog of 15 as the starting materials. mp 256-258° C.; ESIMS (M−H) calc'd for C 18 H 20 N 5 O 3 : 354.1566, found: 354.1543.

Example CXXVI

Preparation of 3-(N-methylcarbamoyl-4-piperidinyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 4-aminomorpholine and the N-methylcarbamoyl-4-piperidinyl analog of 15 as the starting materials. mp 216-218° C.; ESIMS (M+H) calc'd for C 22 H 27 N 6 O 5 : 455.2042, found: 455.2036.

Example CXXVII

Preparation of 3-(5-methyl-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 4-aminomorpholine and the 5-methyl-2-thienyl analog of 15 as the starting materials. mp 261° C.; ESIMS (M+H) calc'd for C 20 H 20 N 5 O 3 S: 410.1287, found: 410.1308.

Example CXXVIII

Preparation of 3-(5-chloro-3-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 4-aminomorpholine and the 5-chloro-3-thienyl analog of 15 as the starting materials. mp 259° C.; ESIMS (M+H) calc'd for C 19 H 17 N 5 O 3 SCl: 430.0741, found: 430.0757.

Example CXXIX

Preparation of 3-(2,5-dimethyl-3-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 4-aminomorpholine and the 2,5-dimethyl-3-thienyl analog of 15 as the starting materials. mp >280° C.; ESIMS (M+H) calc'd for C 21 H 22 N 5 O 3 S: 424.1443, found: 424.1431.

Example CXXX

Preparation of 3-(5-ethylcarboxyl-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 4-aminomorpholine and the 5-ethylcarboxyl-2-thienyl analog of 15 as the starting materials. mp 258° C.; ESIMS (M+H) calc'd for C 22 H 22 N 5 O 5 S: 468.1341, found: 468.1331.

Example CXXXI

Preparation of 3-(5-carboxyl-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI (HYDROLYSIS OF PREVIOUS ESTER). mp 273° C.; ESIMS (M+H) calc'd for C 20 H 18 N 5 O 5 S: 440.1028, found: 440.1026.

Example CXXXII

Preparation of 3-(5-benzylcarboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

A solution of benzylamine (0.01 mL, 0.09 mmol) in DMF (1 mL) was treated with acid CXXXI (40 mg, 0.09 mmol) and stirred at 25° C. The reaction was treated with TBTU (29 mg, 0.09 mmol) and stirred at 25° C. for 30 min. Triethylamine (0.01 mL, 0.09 mmol) was added and the reaction stirred at 25° C. for 12 h. After adding more TBTU (15 mg, 0.045 mmol) and triethylamine (0.01 mL, 0.09 mmol) the reaction was stirred at 25° C. for an additional 4 h. The reaction was diluted with EtOAc (10 mL) and water (10 mL) and the aqueous layer was extracted with EtOAc (5×10 mL). The combined organic layers were dried (Na2SO4), filtered, and the solvent removed at reduced pressure. Purification of the residue using reverse phase HPLC gave the product as a yellow solid (21 mg, 42%). mp 275° C.; ESIMS (M+H) calc'd for C 27 H 25 N 5 O 4 S: 529.1659, found: 529.1682.

Example CXXXIII

Preparation of 3-(5-(4-methylpiperazinyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 1-amino-4-methylpiperazine as the starting material. mp 190° C.; ESIMS (M+H) calc'd for C 25 H 29 N 8 O 4 S: 537.2032, found: 537.2055.

Example CXXXIV

Preparation of 3-(5-(2-(1-methylpyrrolidinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 2-(2-aminoethyl)-1-methylpyrrolidine as the starting material. mp 235° C.; ESIMS (M+H) calc'd for C 27 H 32 N 7 O 4 S: 550.2236, found: 550.2229.

Example CXXXV

Preparation of 3-(5-(N,N-dimethylamino)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 1,1-dimethylhydrazine as the starting material. mp 201° C.; ESIMS (M+H) calc'd for C 22 H 24 N 7 O 4 S: 482.1610, found: 482.1588.

Example CXXXVI

Preparation of 3-(5-(2-(N,N-dimethylamino)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using N,N-dimethylethylenediamine as the starting material. mp 190° C.; ESIMS (M+H) calc'd for C 24 H 28 N 7 O 4 S: 510.1923, found: 510.1922.

Example CXXXVII

Preparation of 3-(5-(2-(pyrrolidinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 1-(2-aminoethyl)pyrrolidine as the starting material. mp 224° C.; ESIMS (M+H) calc'd for C 26 H 30 N 7 O 4 S: 536.2080, found: 536.2091.

Example CXXXVIII

Preparation of 3-(5-(2-(morpholinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 4-(2-aminoethyl)morpholine as the starting material. mp 241° C.; ESIMS (M+H) calc'd for C 26 H 30 N 7 O 5 S: 552.2029, found: 552.2043.

Example CXXXIX

Preparation of 3-(5-morpholinylcarboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 4-aminomorpholine as the starting material. mp 271° C.; ESIMS (M+H) calc'd for C 24 H 26 N 7 O 5 S: 524.1716, found: 524.1719.

Example CXL

Preparation of 3-(5-(3-(pyrrolidonyl)propyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 1-(3-aminopropyl)-2-pyrrolidinone as the starting material. mp 260° C.; ESIMS (M+H) calc'd for C 27 H 30 N 7 O 5 S: 564.2029, found: 564.2031.

Example CXLI

Preparation of 3-(5-(2-(3-pyridyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 3-(2-aminoethyl)pyridine as the starting material. mp 203° C.; ESIMS (M+H) calc'd for C 27 H 26 N 7 O 4 S: 544.1766, found: 544.1760.

Example CXLII

Preparation of 3-(5-(3-(imidazolyl)propyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 1-(3-aminopropyl)imidazole as the starting material. mp 263° C.; ESIMS (M+H) calc'd for C 26 H 27 N 8 O 4 S: 547.1875, found: 547.1872.

Example CXLIII

Preparation of 3-(5-(2-(2-pyridyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 2-(2-aminoethyl)pyridine as the starting material. mp >280° C.; ESIMS (M+H) calc'd for C 27 H 26 N 7 O 4 S: 544.1767, found: 544.1778.

Example CXLIV

Preparation of 3-(5-((2-pyridyl)methyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 2-(aminomethyl)pyridine as the starting material. mp 239° C.; ESIMS (M+H) calc'd for C 26 H 24 N 7 O 4 S: 530.1610, found: 530.1603.

Example CXLV

Preparation of 3-(5-(2-(piperidinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 1-(2-aminoethyl)piperidine as the starting material. mp 228° C.; ESIMS (M+H) calc'd for C 27 H 32 N 7 O 4 S: 550.2236, found: 550.2236.

Example CXLVI

Preparation of 3-(4-(trifluoromethyl)phenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI employing 1-(4-(trifluoromethyl)phenyl)-4,4,4-trifluoro-1,3-butanedione as the starting material. mp >300° C.; ESI − -MS m/e calc'd for C 19 H 11 N 3 O 2 : 370.0804, found: 370.0809.

Example CXLVII

Preparation of 3-(4-(4-t-butoxycarbonyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 30.

A solution of 4-piperazinoacetophenone (24.8 g, 121 mmol) and di-tert-butyl dicarbonate (27.8 g, 128 mmol) in 480 mL of tetrahydrofuran was refluxed for 16 h. After cooling to room temperature the solution was concentrated under vacuum. The resulting solids were washed with hexane and dried under vacuum to afford 29.4 g (80%) of the product as an off-white solid. NMR (CDCl 3 ) δ7.89 (d, 2 H, J=9 Hz), 6.87 (d, 2 H, J=9 Hz), 3.59 (m, 4 H), 3.33 (m, 4 H), 2.53 (s, 3 H), 1.49 (s, 9 H).

Step 2. Synthesis of 31 from 30.

To a solution of 30 (11.35 g, 37 mmol) and ethyl trifluoroacetate (5.40 mL, 45 mmol) in 50 mL of tetrahydrofuran at 25° C. was added dropwise over 15 min. 21% sodium ethoxide in ethanol (16.8 mL, 45 mmol), and the resulting solution then was stirred at 25° C. for 14 h. The reaction mixture was diluted with water, adjusted to pH 5 with conc. hydrochloric acid, and extracted with ethyl acetate. The combined extracts was washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The resulting solid was washed with diethyl ether and dried to furnish 12.1 g (81%) of the product as an orange solid. NMR (CDCl 3 ) δ7.87 (d, 2 H, J=9 Hz), 6.87 (d, 2 H, J=9 Hz), 6.45 (s, 1 H), 3.60 (m, 4 H), 3.41 (m, 4 H), 1.48 (s, 9 H).

Step 3. Synthesis of CXLVII from 31.

Prepared in a similar fashion as described for examples LXXVI and XLII employing 31 and 4-aminomorpholine as starting materials. mp 242° C.; ESI-MS m/e calc'd for C 30 H 36 N 7 O 5 574.2778, found: 574.2762.

Example CXLVIII

Preparation of 3-(4-(1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

A solution of CXLVII (0.58 g, 1.0 mmol) in 20 mL of trifluoroacetic acid was stirred at 25° C. for 2 h. The reaction mixture was concentrated under vacuum, and the residue was recrystallized from ethanol to provide 0.53 g (89%) of the yellow product as its TFA-salt. mp 263° C.; ESI-MS m/e calc'd for C 25 H 28 N 7 O 3 : 474.2254, found: 474.2280.

Example CXLIX

Preparation of 3-(4-(1-piperazinyl)phenyl)-5-((aminocarbonyl)amino)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples XLII and CXLVIII employing 2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedione obtained in example CXLVII and ammonia as the starting materials. mp 257° C.; ESI-MS m/e calc'd for C 21 H 21 N 6 O 2 : 389.1726, found: 389.1724.

Example CL

Preparation of 3-(4-(1-piperazinyl)phenyl)-5-((hydrazinocarbonyl)amino)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples XLII and CXLVIII employing 2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedione obtained in example CXLVII and hydrazine as the starting materials. mp 257° C.; ESI-MS m/e calc'd for C 21 H 22 N 7 O 2 : 404.1835, found: 404.1834.

Example CLI

Preparation of 3-(4-(1-piperazinyl)phenyl)-5-((dimethylamino)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared employing 2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedione obtained in example CXLVII as the starting material. Chloroacetylation and treatment with dimethylamine in a similar fashion as described for examples II and XXIII, followed by treatment with hydrazine and removal of the t-butoxycarbonyl group in a similar fashion as described for examples I and CXLVIII, afforded the example compound. mp 243° C.; ESI-MS m/e calc'd for C 24 H 27 N 6 O 2 : 431.2196, found: 431.2198.

Example CLII

Preparation of 3-(4-(1-piperazinyl)phenyl)-5-((4-morpholinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared employing 2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedione obtained in example CXLVII as the starting material. Chloroacetylation and treatment with morpholine in a similar fashion as described for examples II and XXIII, followed by treatment with hydrazine and removal of the t-butoxycarbonyl group in a similar fashion as described for examples I and CXLVIII, afforded the example compound. mp 259° C.; ESI-MS m/e calc'd for C 26 H 29 N 6 O 3 : 473.2301, found: 473.2302.

Example CLIII

Preparation of 3-(4-(1-piperazinyl)phenyl)-5-((4-methyl-1-piperazinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared employing 2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedione obtained in example CXLVII as the starting material. Chloroacetylation and treatment with 1-methylpiperazine in a similar fashion as described for examples II and XXIII, followed by treatment with hydrazine and removal of the t-butoxycarbonyl group in a similar fashion as described for examples I and CXLVIII, afforded the example compound. ESI-MS m/e calc'd for C 27 H 32 N 7 O 2 : 486.2618, found: 486.2608.

Example CLIV

Preparation of 3-(4-(1-piperazinyl)phenyl)-5-((4-amino methyl-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared employing 2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedione obtained in example CXLVII as the starting material. Chloroacetylation and treatment with 4-(aminomethyl)piperidine in a similar fashion as described for examples II and XXIII, followed by treatment with hydrazine and removal of the t-butoxycarbonyl group in a similar fashion as described for examples I and CXLVIII, afforded the example compound. mp 239° C.; ESI-MS m/e calc'd for C 28 H 34 N 7 O 2 : 500.2774, found: 500.2772.

Example CLV

Preparation of 3-(4-(4-methyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

To a solution of CXLVIII (0.17 g, 0.29 mmol) in 10 mL of methanol and 2 mL of water at 25° C. was added sequentially 37% aqueous formaldehyde (0.45 g, 5.8 mmol), sodium cyanoborohydride (0.18 g, 2.9 mmol), and 4 drops of acetic acid. The resulting solution was stirred at 25° C. for 16 h. The mixture was diluted with water. It then was made acidic (˜pH 1) with conc. hydrochloric acid and stirred for 10 min. The solution next was made basic (˜pH 13) with 50% aqueous sodium hydroxide and finally adjusted to pH 10 with 1 N hydrochloric acid. The mixture was extracted with 4:1 chloroform/isopropanol. The combined extracts were washed with water and brine, dried over anhydrous sodium sulfate, and filtered. To the filtrate was added excess trifluoroacetic acid, and the solution was concentrated under vacuum. The residue was recrystallized from isopropanol to furnish 0.16 g (92%) of the yellow product as its TFA-salt. mp 245° C.; ESI-MS m/e calc'd for C 26 H 30 N 7 O 3 : 488.2410, found: 488.2420.

Example CLVI

Preparation of 3-(4-(4-ethyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLV employing CXLVIII and acetaldehyde as the starting materials. mp 245° C.; ESI-MS m/e calc'd for C 27 H 32 N 7 O 3 : 502.2567, found: 502.2555.

Example CLVII

Preparation of 3-(4-(4-isopropyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLV employing CXLVIII and acetone as the starting materials. mp 253° C.; ESI-MS m/e calc'd for C 28 H 34 N 7 O 3 : 516.2723, found: 516.2726.

Example CLVIII

Preparation of 3-(4-methoxyphenyl)-5-(2-benzoylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 31 from 13.

A suspension of aniline 31 (0.5 g, 1.7 mmol) in dioxane (10 mL) was treated with triethylamine (0.48 mL, 3.4 mmol) in one portion at room temperature. Then 2-(trimethylsilyl) ethyloxy chloride (SEMCl) (0.48 mL, 2.6 mmol) was added in one portion and the mixture heated to reflux for 2 h. The reaction was cooled, diluted with EtOAc (20 mL) washed with water (10 mL), dried (MgSO4) and the solvent removed at reduced pressure. The residue was taken up in benzene (3 mL), applied to a plug of silica gel (10 g) and eluted with EtOAc/Hexane (1:3) until all the yellow color was washed from the silica gel plug. The solvent was evaporated and the residue taken on to the next step. This material was dissolved in dioxane (10 mL) and treated with K2CO3 (0.36 g, 2.6 mmol) in one portion. Then phenylchloroformate (0.27 mL, 2.23 mmol) was added in one portion and the reaction heated to 50 C. for 2 h. The reaction was cooled and the solvent removed at reduced pressure. The residue was recrystalized from EtOH to give a yellow solid (0.4 g, 43%). mp °C.; CIMS m/e calculated for C 30 H 32 N 3 O 5 Si: 542.2111, found: 542.2101;

Step 2. Synthesis of Ex. CLVIII from 31.

Compound 31 (0.015 g, 0.03 mmol) in DMSO (0.2 mL) was treated with phenylcarbazte (0.008 g, 0.06 mmol) in one portion and heated to 80 C. for 30 minutes. The solvent was removed at reduced pressure heating to 65 C. The residue was disolved in EtOH (0.5 mL) and treated with 4N HCl/dioxane (0.4 mL). The mixture was heated to 80 C. for 20 minutes and then cooled. The desired product was filtered and air dried (0.008 g, 62%). mp >300° C.; CIMS m/e calculated for C 26 H 27 N 4 O 4 : 459.2032, found: 459.1999;

Example CLIX

Preparation of 3-(4-methoxyphenyl)-5-(2-isonicotinoylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using 4-pyridylcarbazate as the starting material. mp 248° C.; CIMS m/e calculated for C 24 H 19 N 6 O 4 : 455.1468, found: 455.1400;

Example CLX

Preparation of 3-(4-methoxyphenyl)-5-(2-nictinoylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using 3-pyridylcarbazate as the starting material. mp 227° C.; CIMS m/e calc'd for C 24 H 19 N 6 O 4 : 455.1468, found: 455.1487;

Example CLXI

Preparation of 3-(4-methoxyphenyl)-5-(2-(3,4-dihydroxy benzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using 3,4-dihydroxyphenyl carbazate as the starting material. mp >300° C.; CIMS m/e calc'd for C 25 H 20 N 5 O 6 : 486.1414, found: 486.1497;

Example CLXII

Preparation of 3-(4-methoxyphenyl)-5-(2-(4-hydroxy benzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using 4-hydroxyphenyl carbazate as the starting material. mp 283° C.; CIMS m/e calc'd for C 25 H 20 N 5 O 5 : 470.1464, found: 470.1544;

Example CLXIII

Preparation of 3-(4-methoxyphenyl)-5-(2-(3-aminobenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using 3-aminophenyl carbazate as the starting material. mp 250° C.; CIMS m/e calc'd for C 25 H 21 N 6 O 4 : 469.1624, found: 469.1513;

Example CLXIV

Preparation of 3-(4-methoxyphenyl)-5-(2-(4-aminobenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using 4-aminophenyl carbazate as the starting material. mp 247° C.; CIMS m/e calc'd for C 25 H 21 N 6 O 4 : 469.1624, found: 469.1528;

Example CLXV

Preparation of 3-(4-methoxyphenyl)-5-(2-(2-aminobenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using 2-aminophenyl carbazate as the starting material. mp 257° C.; CIMS m/e calc'd for C 25 H 21 N 6 O 4 : 469.1624, found: 469.1548;

Example CLXVI

Preparation of 3-(4-methoxyphenyl)-5-(2-(4-N,N-dimethylamino benzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using 4-N,N-dimethylaminophenyl carbazate as the starting material. mp 259° C.; CIMS m/e calc'd for C 27 H 25 N 6 O 4 : 497.1937, found: 497.1876;

Example CLXVII

Preparation of 3-(4-methoxyphenyl)-5-(2-phenethylacetyl hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using benzyl carbazate as the starting material. mp 269° C.; CIMS m/e calc'd for C 26 H 22 N 5 O 4 : 468.1672, found: 468.1313;

Example CLXVIII

Preparation of 3-(4-methoxyphenyl)-5-(2-(2-hydroxybenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using 2-hydroxyphenyl carbazate as the starting material. mp 280° C.; CIMS m/e calc'd for C 25 H 20 N 5 O 5 : 470.1464, found: 470.1419;

Example CLXIX

Preparation of 3-(4-methoxyphenyl)-5-(2-methoxycarbonylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using carbazic acid methyl ester as the starting material. mp >300° C.; CIMS m/e calc'd for C 20 H 28 N 5 O 5 : 408.1308, found: 408.1397;

EXAMPLE CLXX

Preparation of Intermediate CLXX

The preparation of intermediate CLXX, (N-[2-(4-Methoxy-benzoyl)-1,3-dioxo-indan-4-yl]-acetamide) is described in Nugiel, D. A.; Etzkorn, A. M.; Vidwans, A.; Benfield, P. A.; Boisclair, M.; Burton, C. R.; Cox, S.; Czerniak, P. M.; Doleniak, D.; Seitz, S. P. J. Med. Chem. 2001, 44, 1334-1336 which is herein incorporated by reference in it's entirety as though set forth in full.

EXAMPLE CLXXI

Preparation of Intermediate CLXXI

Synthesis of 4-Amino-2-(4-methoxy-benzoyl)-indan-1,3-dione: The compound prepared in example 1 (2.0 g, 5.93 mmol) is dissolved in 20% HCl in methanol (50 mL). This solution is stirred at reflux for a period of 3 h. It is then allowed to cool to room temperature and stirred overnight. The product is filtered off, washed with ethanol (20 mL) and air dried to give the product as a yellow solid (1.5 g, 85.7%). mp 268-269° C.; 1 H NMR (DMSOd 6 ) δ8.17 (d, J=8.8 Hz, 2H), 7.49 (t, 1H), 7.12 (d, J=8.7 Hz, 2H), 6.98 (m, 2H), 3.88 (s, 1H).

EXAMPLE CLXXII

Preparation of Intermediate CLXXII

Synthesis of [2-(4-Methoxybenzoyl)-1,3-dioxo-indan-4-yl]-carbamic acid phenyl ester: The product prepared in Example CLXXI (1.5 g, 5.08 mmol) is dissolved in acetone (40 mL) and treated with sodium carbonate (1.26 g, 15.24 mmol) and phenyl chloroformate (1.19 g, 7.62 mmol). The suspension is stirred at 50° C. for 3 h. The reaction mixture is diluted with water (120 mL), and extracted with ethyl acetate (2×100 mL). The organic layer is separated, washed with brine (50 mL), dried (Na 2 SO 4 ) and the solvent removed at reduced pressure to give a gummy orange residue. Cold ethyl ether (100 mL) is added to this residue to give a precipitate. The precipitate is collected and washed with ethyl ether (2×10 mL) to give desired product as a yellow solid (1.65 g. 78%). mp 256-258° C.; 1 H NMR (DMSOd 6 ) δ10.83 (s, 1H), 8.08 (d, J=8.0 Hz, 1H), 7.57 (d, J=2.9 Hz, 2H), 7.54 (m, 3H), 7.28 (m, 3H), 7.09 (t, 1H), 6.89 (d, J=10.8 Hz, 2H), 3.81 (s, 3H).

EXAMPLE CLXXIII

Preparation of 1-[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-3-morpholin-4-yl-urea

The product prepared in Example CLXXII (0.03 g, 0.072 mmol) in anhydrous DMSO (2 mL) is treated with 4-aminomorpholine (0.0084 g, 0.082 mmol) and 4-dimethylaminopyridine (0.005 g, 0.04 mmol) and heated to 80° C. for 3 h. The solvent is removed under reduced pressure and the residue triturated with ethanol to give a dark solid. The solid is collected and washed with ethanol (5 mL) to give a tricarbonyl urea (0.03 g, 100%). The tricarbonyl urea intermediate (0.03 g, 0.078 mmol) is treated with hydrazine hydrate (0.1 mL, 3.21 mmol) and p-toluenesulfonic acid monohydrate (0.01 g, 0.05 mmol) in refluxing ethanol (4 mL) for a period of 3 h. The reaction mixture is cooled to room temperature, the solid collected, washed with cold ethanol (2×2 mL), and air dried to give the product as a yellowish solid (0.012 g, 41.3%). mp 290-291° C.; 1 H NMR (DMSO-d 6 ) δ8.27 (d, J=6.8 Hz, 2H), 8.16 (d, J=8.8 Hz, 2H), 7.42 (m, 1H), 7.12 (m, 3H), 3.81 (s, 3H), 2.90 (s, 4H), 2.70 (s, 4H), HRMS calcd. for C 22 H 22 N 5 O 4 (M+H + ) 420.1672; found 420.1688;

EXAMPLE CLXXIV

Preparation of [3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-urea

The product prepared in Example CLXXII (0.03 g, 0.072 mmol) in anhydrous DMSO (2 mL) is treated with excess ammonium hydroxide solution and 4-dimethylaminopyridine (0.005 g, 0.04 mmol) and is heated to 80° C. for 3 h. The solvent is removed under reduced pressure and the residue triturated with ethanol to give a dark solid. The solid is collected and washed with ethanol (5 mL) to give urea (0.03 g, 100%). The tricarbonyl urea intermediate (0.03 g, 0.078 mmol) is treated with hydrazine hydrate (0.1 mL, 3.21 mmol) and p-toluenesulfonic acid monohydrate (0.01 g, 0.05 mmol) in refluxing ethanol (4 mL) for a period of 3 h. The reaction mixture is cooled to room temperature, the solid collected, washed with cold ethanol (2×2 mL), and air dried to give the product as a yellowish solid (0.018 g, 62.4%). mp 267-269° C.; 1 H NMR (DMSO-d 6 ) δ9.35 (s, 1H), 8.22 (m, 3H), 7.38 (m, 1H), 7.10 (d, J=8.8 Hz, 2H), 7.02 (d, J=7 Hz, 1H), 3.81 (s, 3H); HRMS calcd. for C 18 H 15 N 4 O 3 (M+H + ) 335.1144; found 335.1162;

EXAMPLE CLXXV

Preparation of 1-(2-amino-cyclohexyl)-3-[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-urea

The product prepared in Example CLXXII (0.03 g, 0.072 mmol) in anhydrous DMSO (2 mL) is treated with 1,2-diaminocyclohexane (0.01 g, 0.082 mmol) and 4-dimethylaminopyridine (0.005 g, 0.04 mmol) and heated to 80° C. for 3 h. The solvent is removed under reduced pressure and the residue triturated with ethanol to give a dark solid. The solid is collected and washed with ethanol (5 mL) to give a tricarbonyl urea (0.03 g, 100%). The tricarbonyl urea intermediate (0.03 g, 0.078 mmol) is treated with hydrazine hydrate (0.1 mL, 3.21 mmol) and p-toluenesulfonic acid monohydrate (0.01 g, 0.05 mmol) in refluxing ethanol (4 mL) for a period of 3 h. The reaction mixture is cooled to room temperature, the solid collected, washed with cold ethanol (2×2 mL), and air dried to give the product as a yellowish solid (0.01 g, 30.6%). 1 HNMR (DMSO-d 6 ) δ9.56 (s, 1H), 8.27 (d, 1H), 8.19 (d, 2H), 7.41 (t, 1H), 7.10 (m, 3H), 4.10 (s, 1H), 3.81 (s, 3H), 3.23 (s, 1H), 1.63 (m, 5H), 1.40 (m, 3H).

EXAMPLE CLXXVI

Preparation of 5-Amino-3-(4-methoxyphenyl)-2-phenyl-2H-indeno-[1,2-c]pyrazol-4-one:

A suspension of N-[3-(4-Methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-acetamide (as produced according to Nugiel, D. A.; Etzkorn, A. M.; Vidwans, A.; Benfield, P. A.; Boisclair, M.; Burton, C. R.; Cox, S.; Czerniak, P. M.; Doleniak, D.; Seitz, S. P. J. Med. Chem. 2001, 44, 1334-1336) (1.0 g, 3.0 mmol) in MeOH (10 mL) was treated with concentrated HCl (1 mL) and heated to reflux. After stirring the mixture for 2 h the reaction was cooled and the product was collected by filtration and obtained as a greenish solid (0.7 g, 81%). mp 273° C.; NMR (DMSO-d 6 ) δ13.6 (bs, 1 H), 8.3 (d, J=8.4 Hz, 1 H), 8.1 (d, J=8.8 Hz, 2 H), 7.5 (t, J=7.7 Hz 1 H), 7.2 (d, J=7.0 Hz, 1 H), 7.1 (d, J=8.8 Hz, 2 H), 3.8 (s, 3 H); HRMS m/e calc'd for C 17 H 14 N 3 O 2 (M+H): 292.1086, found: 292.1080.

EXAMPLE CLXXVII

Preparation of 2-Chloro-N-[3-(4-methoxyphenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-acetamide

A suspension of the product prepared in Example CLXXVI (0.2 g, 0.7 mmol) in dioxane (10 mL) was treated with aqueous saturated NaHCO 3 (3 mL) and chloroacetyl chloride (3 mL, 0.21 mmol). The reaction was heated to 50° C. and stirred for 2 h. The reaction is then cooled, poured into water (20 mL), extracted with EtOAc (100 mL), the organic layer separated, dried (MgSO 4 ) and the solvent removed at reduced pressure. The residue is recrystallized from EtOH to give the product as a yellow solid (0.09 g, 35%). mp >300° C.; NMR (DMSO-d 6 ) δ13.6 (bs, 1 H), 11.3 (s, 1 H), 8.3 (d, J=8.4 Hz, 1 H), 8.1 (d, J=8.8 Hz, 2 H), 7.5 (t, J=7.7 Hz 1 H), 7.2 (d, J=7.0 Hz, 1 H), 7.1 (d, J=8.8 Hz, 2 H), 4.5 (s, 2 H), 3.8 (s, 3 H); HRMS m/e calc'd for C 19 H 15 N 3 O 3 Cl (M+H): 368.0802, found: 368.0818.

EXAMPLE CLXXVIII

Preparation of 2-(4-aminomethyl-piperidin-1-yl)-N-[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-acetamide

A suspension of product prepared according to Example CLXXVII (0.015 g, 0.04 mmol) in EtOH (1 mL) is treated with 4-aminomethylpiperdine (0.75 mL), placed in a sealed tube and heated to 80° C. for 3 h. The reaction is cooled and the solvent removed at reduced pressure. The residue is recrystallized from EtOH to give the product as a yellow solid (0.009 g, 62%). mp >300° C.; NMR (DMSO-d 6 ) δ13.6 (bs, 1 H), 11.3 (s, 1 H), 8.35 (d, J=8.4 Hz, 1 H), 8.1 (d, J=8.8 Hz, 2 H), 7.5 (t, J=7.7 Hz 1 H), 7.2 (d, J=7.0 Hz, 1 H), 7.1 (d, J=8.8 Hz, 2 H), 3.8 (s, 3 H), 3.2 (bs, 2 H), 2.9(bs, 2 H), 2.5 (d, J=8.0 Hz, 2 H), 2.2 (t, J=8.0 Hz, 2 H), 1.6 (m, 5 H); HRMS m/e calc'd for C 25 H 28 N 5 O 3 (M+H): 446.2192, found: 446.2169; Anal. (C 25 H 27 N 5 O 3 ) C, H, N.

EXAMPLE CLXXIX

Preparation of 2-(4-Methoxybenzoyl)-3-methoxycarbonylamino-indan-1,3-dione

A solution of 3-methoxycarbonylamino-phthalic acid dimethyl ester (1 g, 4.8 mmol) and 4-methoxyacetophenone (0.72 g, 4.8 mmol) in dry DMF (3 mL) was heated to 90° C. Sodium hydride (0.21 g, 60% suspension in oil, 5.2 mmol) is added in one portion and the exothermic reaction turns deep red. After 20 min, the reaction is cooled to room temperature, diluted with water (25 mL) extracted with EtOAc (10 mL) and the aqueous phase separated. The aqueous phase is acidified to pH 2 with 2N HCl and the crude product collected. Recrystallization with ethanol gives the desired product as a yellow solid (0.4 g, 30%). ESIMS 352 (M−H, 100%).

EXAMPLE CLXXX

Preparation of 3-(4-Methoxyphenyl)-5-methoxycarbonylamino-2H-indeno-[1,2-c]pyrazol-4-one

A solution of 2-(4-methoxybenzoyl)-3-methoxycarbonylamino-indan-1,3-dione (0.2 g, 0.6 mmol) in EtOH (5 mL) is treated with hydrazine hydrate (0.1 mL, 1.8 mmol) and p-TsOH (3 mg). The reaction is heated to reflux and stirred for 2 h. The reaction is cooled to room temperature and the product crystallized from the reaction mixture. The product is collected by filtration as a yellow solid (0.1 g, 50%). mp >300° C.; HRMS m/e calc'd for C 19 H 16 N 3 O 4 (M+H): 350.1141, found: 350.1168.

Utility

Inhibition of Kinase/Cyclin Complex Enzymatic Activity

Several of the compounds disclosed in this invention were assayed for their inhibitory activity against cdk4/D1 and cdk2/E kinase complexes. Briefly, the in vitro assays employ cell lysates from insect cells expressing either of the kinases and subsequently their corresponding regulatory units. The cdk2/cyclinE is purified from insect cells expressing His-tagged cdk2 and cyclin E. The cdk/cyclin lysate is combined in a microtitre-type plate along with a kinase compatible buffer, 32 P-labeled ATP at a concentration of 50 mM, a GST-Rb fusion protein and the test compound at varying concentrations. The kinase reaction is allowed to proceeded with the radiolabled ATP, then effectively stopped by the addition of a large excess of EDTA and unlabeled ATP. The GST-Rb labeled protein is sequestered on a GSH-Sepharose bead suspension, washed, resuspended in scintillant, and the 32 P activity detected in a scintillation counter. The compound concentration which inhibits 50% of the kinase activity was calculated for each compound. A compound was considered active if its IC 50 was found to be less than 1 μM.

Inhibition of HCT 116 Cancer Cell Proliferation

To test the cellular activity of several compounds disclosed in this invention, we examined the effect of these compounds on cultured HCT116 cells and determined their effect on cell-cycle progression by the calorimetric cytotoxcity test using sulforhodamine B (Skehan et al. J. Natl. Cancer Inst. 82:1107-12, 1990). Briefly, HCT116 cells are cultured in the presence of test compounds at increasing concentrations. At selected time points, groups of cells are fixed with trichloroacetic acid and stained with sulforhodamine B (SRB). Unbound dye was removed by washing and protein-bound dye was extracted for determination of optical density. A compound was considered active if its IC 50 was found to be less than 10 μM.

TABLE 1
Example			mass	mp
#	R 1	R 2	(M + H)	(° C.)
I	Methyl	4-MeOC 6 H 4	334	268
II	ClCH 2	4-MeOC 6 H 4	382	274
III	Cyclopropyl	4-MeOC 6 H 4	360	289
IV	Isopropyl	4-MeOC 6 H 4	362	288
V	Ethyl	4-MeOC 6 H 4	348	287
VI	Cyclopentyl	4-MeOC 6 H 4	388	267
VII	Cyclobutyl	4-MeOC 6 H 4	374	297
VIII	Benzyl	4-MeOC 6 H 4	410	280
IX	n-propyl	4-MeOC 6 H 4	362	282
X	4-ClC 6 H 4 CH 2	4-MeOC 6 H 4	444	238
XI	3-MeOC 6 H 4 CH 2	4-MeOC 6 H 4	440	>300
XII	4-MeOC 6 H 4 CH 2	4-MeOC 6 H 4	440	280
XIII	3,4-diMeOC 6 H 4 CH 2	4-MeOC 6 H 4	470	>300
XIV	2,5-diMeOC 6 H 4 CH 2	4-MeOC 6 H 4	470	226
XV	Methyl	2-MeOC 6 H 4	334	276
XVI	Methyl	3,4-diMeOC 6 H 4	364	>300
XVII	3,4-(OCH 2 O)C 6 H 4 CH 2	4-MeOC 6 H 4	454	297
XVIII	3-thiophenylCH 2	4-MeOC 6 H 4	416	293
XIX	2-MeOC 6 H 4 CH 2	4-MeOC 6 H 4	440	255
XX	3,4-diClOC 6 H 4 CH 2	4-MeOC 6 H 4	479	299
XXI	2,4-diClOC 6 H 4 CH 2	4-MeOC 6 H 4	479	286
XXII	2-ClC 6 H 4 CH 2	4-MeOC 6 H 4	444	300
XXIII	H 2 NCH 2	4-MeOC 6 H 4	349	>300
XXIV	HOCH 2 CH 2 NHCH 2	4-MeOC 6 H 4	393	243
XXV	Me 2 NCH 2	4-MeOC 6 H 4	377	279
XXVI	piperazinylCH 2	4-MeOC 6 H 4	418	277
XXVII	4-Me-piperazinylCH 2	4-MeOC 6 H 4	432	>300
XXVIII	4-HOCH 2 CH 2 -	4-MeOC 6 H 4	462	>300
	piperazinylCH 2
XXIX	piperidinylCH 2	4-MeOC 6 H 4	417	291
XXX	4-NH 2 CH 2 -	4-MeOC 6 H 4	446	>300
	piperidinylCH 2
XXXI	CH 3 CH 2 NHCH 2	4-MeOC 6 H 4	377	250
XXXII	ThiomorpholinylCH 2	4-MeOC 6 H 4	435	298
XXXIII	morpholinylCH 2	4-MeOC 6 H 4	419	295
XXXIV	pyrrolidinylCH 2	4-MeOC 6 H 4	403	279
XXXV	4-pyridylCH 2 NHCH 2	4-MeOC 6 H 4	440	>300
XXXVI	4-CH 3 CONHC 6 H 4 CH 2	4-MeOC 6 H 4	467	268
XXXVII	4-CH 3 OCONHC 6 H 4 CH 2	4-MeOC 6 H 4	483	257
XXXVIII	4-NH 2 CH 2 CONHC 6 H 4 CH 2	4-MeOC 6 H 4	482	228
XXXIX	4-Me 2 NCH 2 CONHC 6 H 4 CH 2	4-MeOC 6 H 4	510	>300
XL	4-N 3 C 6 H 4 CH 2	4-MeOC 6 H 4	451	>300
XLI	4-NH 2 C 6 H 4 CH 2	4-MeOC 6 H 4	425	283
XLII	C 6 H 5 NH	4-MeOC 6 H 4	411	>300
XLIII	CH 3 CH 2 CH 2 NH	4-MeOC 6 H 4	377	252
XLIV	4-NH 2 C 6 H 4 CH 2 NH	4-MeOC 6 H 4	440	>300
XLV	4-pyridylCH 2 NH	4-MeOC 6 H 4	426	>300
XLVI	Methyl	4-HOC 6 H 4	320	>300
XLVII	H	4-MeOC 6 H 4	320	280
XLVIII	Methyl	3-pyridyl	305	>300
XLIX	Methyl	4-pyridyl	305	>300
L	H	4-pyridyl	291	>300
LI	Methyl	C 6 H 5	305	>300
LII	Methyl	4-MeSC 6 H 4	351	283
LIII	Methyl	4-MeSO 2 C 6 H 4	383	>300
LVI	Methyl	4-Me 2 NC 6 H 4	348	>300
LV	morpholinylCH 2	4-Me 2 NC 6 H 4	432	>300
LVI	Me 2 NCH 2	4-Me 2 NC 6 H 4	390	>300
LVII	Methyl	4-(piperdinyl)C 6 H 4	388	291
LVIII	Methyl	4-(morpholinyl)C 6 H 4	389	>300
LIX	Methyl	4-CH 3 CH 2 OC 6 H 4	349	288
LX	Methyl	4-CH 3 CH 2 CH 2 CH 2 C 6 H 4	361	259
LXI	Methyl	4-CH 3 CH 2 C 6 H 4	332	294
LXII	Methyl	4-CH 3 CH 2 CH 2 C 6 H 4	347	269
LXIII	NH 2	4-MeOC 6 H 4	335	>300
LXIV	Me2NNH	4-MeOC 6 H 4	378	>300
LXV	MeNH	4-MeOC 6 H 4	349	>300
LXVI	MorpholinylNH	4-MeOC 6 H 4	420	>300
LXVII	cis-1,2-	4-MeOC 6 H 4	432	>300
	diaminocyclohexanyl
LXVIII	4-methyl-	4-MeOC 6 H 4	433	>300
	piperazinylNH
LXVIX	4-uridomethyl-	4-MeOC 6 H 4	489	>300
	piperadinylCH 2
LXX	4-(2-pyridyl)-	4-MeOC 6 H 4	495	>300
	piperazinyl CH 2
LXXI	4-(aminoethyl)-	4-MeOC 6 H 4	461	>300
	piperazinyl CH 2
LXXII	4-amidopiperidinylCH 2	4-MeOC 6 H 4	460	>300
LXXIII	4-hydroxy-	4-MeOC 6 H 4	433	>300
	piperidinylCH 2
LXXIV	4-hydroxy-	4-MeOC 6 H 4	447	>300
	methylpiperidinylCH 2
LXXV	4-amidopiperazinylCH 2	4-MeOC 6 H 4	493	>300
LXXVI	4-dimethyl-	4-MeOC 6 H 4	492	>300
	aminopiperadinylCH 2
LXXVII	4-aminopiperadinylCH 2	4-MeOC 6 H 4	464	>300
LXXVIII	4-Me-piperazinylCH 2	4-Me 2 NC 6 H 4	445	>300
LXXIX	4-NH 2 CH 2 -	4-Me 2 NC 6 H 4	459	NA
	piperidinylCH 2
LXXX	4-OH-piperidinylCH 2	4-Me 2 NC 6 H 4	446	267
LXXXI	morpholinylCH 2	4-(morpholinyl)C 6 H 4	474	258
LXXXII	4-Me-piperazinylCH 2	4-(morpholinyl)C 6 H 4	487	258
LXXXIII	4-OH-piperidinylCH 2	4-(morpholinyl)C 6 H 4	488	245
LXXXIV	4-NH 2 CH 2 -	4-(morpholinyl)C 6 H 4	501	240
	piperidinylCH 2
LXXXV	4-Me-piperazinylNH	4-Me 2 NC 6 H 4	446	>300
LXXXVI	Methyl	i-propyl	270	>250
LXXXVII	Methyl	c-propyl	268	220
LXXXVIII	Methyl	t-butyl	284	>250
LXXXIX	Methyl	2-thienyl	310	269
XC	Methyl	3-Me-2-thienyl	324	275
XCI	NH 2	Ethyl	257	>250
XCII	NH 2	n-propyl	271	187
XCIII	NH 2	i-propyl	271	>250
XCIV	NH 2	c-propyl	267	252
			(M − H)
XCV	NH 2	c-hexyl	311	178
XCVI	NH 2	2-thienyl	310	214
			(M+)
XCVII	NH 2	3-Me-2-thienyl	325	270
XCVIII	NH 2	5-Me-2-thienyl	325	>280
XCIX	NH 2	5-CO 2 Et-2-thienyl	383	>280
C	NH 2	3-thienyl	311	>280
CI	NH 2	5-Cl-3-thienyl	345	>300
CII	NH 2	2,5-diMe-3-thienyl	339	>280
CIII	NH 2	2-furanyl	295	278
CIV	Me 2 NNH	i-propyl	314	231
CV	Me 2 NNH	c-propyl	312
CVI	Me 2 NNH	c-hexyl	354	229
CVII	Me 2 NNH	2-thienyl	354	279
CVIII	Me 2 NNH	5-MeO-2-thienyl	384	280
CIX	Me 2 NNH	5-Me-2-thienyl	368	>280
CX	Me 2 NNH	5-CO 2 Et-2-thienyl	426	252
CXI	Me 2 NNH	3-thienyl	354	202
CXII	NH 2	1-methyl-3-	308	>300
		pyrrolyl
CXIII	Me 2 NNH	2,5-diMe-3-thienyl	382	252
CXIV	Me 2 NNH	2-furanyl	338	202
CXV	4-NH 2 CO-	i-propyl	396	224
	piperidinylCH 2
CXVI	4-NH 2 CO-	c-hexyl	436	228
	piperidinylCH 2
CXVII	4-NH 2 CH 2 -	ethyl	368	174
	piperidinylCH 2
CXVIII	4-NH 2 CH 2 -	1-propyl	382	218
	piperidinylCH 2
CXVIX	4-NH 2 CH 2 -	c-propyl	380	138
	piperidinylCH 2
CXX	4-NH 2 CH 2 -	c-hexyl	422	196
	piperidinylCH 2
CXXI	4-CH 3 -piperazinylNH	i-propyl	369	231
CXXII	4-CH 3 -piperazinylNH	5-CO 2 Et-2-thienyl	481	249
CXXIII	4-CH 3 -piperazinylNH	5-CO 2 H-2-thienyl	453	270
CXXIV	4-CH 3 -piperazinylNH	2,5-diMe-3-thienyl	437	250
CXXV	MorpholinylNH	i-propyl	354	256
			(M − H)
CXXVI	MorpholinylNH	4-CO 2 Me-	455	216
		piperidinyl
CXXVII	MorpholinylNH	5-Me-2-thienyl	410	261
CXXVIII	MorpholinylNH	5-Cl-3-thienyl	430	259
CXXIX	MorpholinylNH	2,5-diMe-3-thienyl	424	>280
CXXX	MorpholinylNH	5-CO 2 Et-2-thienyl	468	258
CXXXI	MorpholinylNH	5-CO 2 H-2-thienyl	440	273
CXXXII	MorpholinylNH	5-CONHBn-2-thienyl	529	275
CXXXIII	MorpholinylNH	5-CONH(4-Me-	537	190
		piperazinyl)-2-
		thienyl
CXXXIV	MorpholinylNH	5-CONHCH 2 CH 2 (1-Me-	550	235
		2-pyrrolidinyl)-2-thienyl
CXXXV	MorpholinylNH	5-CONHNMe 2 -2-thienyl	482	201
CXXXVI	MorpholinylNH	5-CONHCH 2 CH 2 NMe 2 -	510	190
		2-thienyl
CXXXVII	MorpholinylNH	5-CONHCH 2 CH 2 (1-	536	224
		pyrrolidinyl)-2-thienyl
CXXXVIII	MorpholinylNH	5-CONHCH 2 CH 2 (1-	552	241
		morpholinyl)-2-thienyl
CXXXIX	MorpholinylNH	5-CONHmorpholinyl-2-thienyl	524	271
CXL	MorpholinylNH	5-CONHCH 2 CH 2 CH 2 (1-	564	260
		pyrrolidonyl)-2-thienyl
CXLI	MorpholinylNH	5-CONHCH 2 CH 2 (3-	544	203
		pyridyl)-2-thienyl
CXLII	MorpholinylNH	5-CONHCH 2 CH 2 CH 2 (1-	547	263
		imidazolyl)-2-thienyl
CXLIII	MorpholinylNH	5-CONHCH 2 CH 2 (2-	544	>280
		pyridyl)-2-thienyl
CXLIV	MorpholinylNH	5-CONHCH 2 (3-	530	239
		pyridyl)-2-thienyl
CXLV	MorpholinylNH	5-CONHCH 2 CH 2 (1-	550	228
		piperidinyl)-2-thienyl
CXLVI	Methyl	4-CF 3 C 6 H 4	370	>300
			(M − H)
CXLVII	MorpholinylNH	4-(4-Boc-	574	242
		piperazinyl)C 6 H 4
CXLVIII	MorpholinylNH	4-(piperazinyl)C 6 H 4	474	263
CXLIX	NH 2	4-(piperazinyl)C 6 H 4	389	257
CL	NH 2 NH	4-(piperazinyl)C 6 H 4	404	257
CLI	Me 2 NCH 2	4-(piperazinyl)C 6 H 4	431	243
CLII	morpholinylCH 2	4-(piperazinyl)C 6 H 4	473	259
CLIII	4-Me-piperazinylCH 2	4-(piperazinyl)C 6 H 4	486	NA
CLIV	4-NH 2 CH 2 -	4-(piperazinyl)C 6 H 4	500	239
	piperidinylCH 2
CLV	MorpholinylNH	4-(4-Me-	488	245
		piperazinyl)C 6 H 4
CLVI	MorpholinylNH	4-(4-Et-	502	245
		piperazinyl)C 6 H 4
CLVII	MorpholinylNH	4-(4-i-Pr-	516	253
		piperazinyl)C 6 H 4
CLVIII	C 6 H 5 C(O)NHNH	4-MeOC 6 H 4	459	>300
CLIX	4-pyridylC(O)NHNH	4-MeOC 6 H 4	455	248
CLX	3-pyridylC(O)NHNH	4-MeOC 6 H 4	455	227
CLXI	3,4-dihydroxy-	4-MeOC 6 H 4	486	>300
	C 6 H 3 C(O)NHNH
CLXII	4-hydroxy-	4-MeOC 6 H 4	470	283
	C 6 H 4 C(O)NHNH
CLXIII	3-amino-C 6 H 4 C(O)NHNH	4-MeOC 6 H 4	469	250
CLXIV	4-amino-C 6 H 4 C(O)NHNH	4-MeOC 6 H 4	469	247
CLXV	2-amino-C 6 H 4 C(O)NHNH	4-MeOC 6 H 4	469	257
CLXVI	4-N,N-dimethylamino-	4-MeOC 6 H 4	497	259
	C 6 H 4 C(O)NHNH
CLXVII	C 6 H 5 CH 2 C(O)NHNH	4-MeOC 6 H 4	468	269
CLXVIII	2-hydroxy-	4-MeOC 6 H 4	470	280
	C 6 H 4 C(O)NHNH
CLXIX	MeOC(O)NHNH	4-MeOC 6 H 4	408	>300

TABLE 2
Example
Number	R 1	R 2
100	2-pyridylmethyl	4-MeOC 6 H 4
101	2-pyridylmethyl	3-MeOC 6 H 4
102	2-pyridylmethyl	4-NH 2 C 6 H 4
103	2-pyridylmethyl	3-NH 2 C 6 H 4
104	2-pyridylmethyl	2-NH 2 C 6 H 4
105	2-pyridylmethyl	4-Me 2 NC 6 H 4
106	2-pyridylmethyl	3-Me 2 NC 6 H 4
107	2-pyridylmethyl	2-Me 2 NC 6 H 4
108	2-pyridylmethyl	4-pyridyl
109	2-pyridylmethyl	3-pyridyl
110	2-pyridylmethyl	2-pyridyl
111	2-pyridylmethyl	2-thiazolyl
112	2-pyridylmethyl	2-pyrazolyl
113	2-pyridylmethyl	5-isoquinolyl
114	2-pyridylmethyl	3,4-methylenedioxyC 6 H 3
115	2-pyridylmethyl	3,4-ethylenedioxyC 6 H 3
116	2-pyridylmethyl	2-imidazolyl
117	2-pyridylmethyl	2-oxazolyl
118	2-pyridylmethyl	4-isoxazolyl
119	2-pyridylmethyl	4-HOC 6 H 4
120	2-pyridylmethyl	3-HOC 6 H 4
121	2-pyridylmethyl	3,4-diHOC 6 H 4
122	2-pyridylmethyl	4-NH 2 CH 2 C 6 H 4
123	2-pyridylmethyl	3-NH 2 CH 2 C 6 H 4
124	3-pyridylmethyl	4-MeOC 6 H 4
125	3-pyridylmethyl	3-MeOC 6 H 4
126	3-pyridylmethyl	4-NH 2 C 6 H 4
127	3-pyridylmethyl	3-NH 2 C 6 H 4
128	3-pyridylmethyl	2-NH 2 C 6 H 4
129	3-pyridylmethyl	4-Me 2 NC 6 H 4
130	3-pyridylmethyl	3-Me 2 NC 6 H 4
131	3-pyridylmethyl	2-Me 2 NC 6 H 4
132	3-pyridylmethyl	4-pyridyl
133	3-pyridylmethyl	3-pyridyl
134	3-pyridylmethyl	2-pyridyl
135	3-pyridylmethyl	2-thiazolyl
136	3-pyridylmethyl	2-pyrazolyl
137	3-pyridylmethyl	5-isoquinolyl
138	3-pyridylmethyl	3,4-methylenedioxyC 6 H 3
139	3-pyridylmethyl	3,4-ethylenedioxyC 6 H 3
140	3-pyridylmethyl	2-imidazolyl
141	3-pyridylmethyl	2-oxazolyl
142	3-pyridylmethyl	4-isoxazolyl
143	3-pyridylmethyl	4-HOC 6 H 4
144	3-pyridylmethyl	3-HOC 6 H 4
145	3-pyridylmethyl	3,4-diHOC 6 H 4
146	3-pyridylmethyl	4-NH 2 CH 2 C 6 H 4
147	3-pyridylmethyl	3-NH 2 CH 2 C 6 H 4
148	4-pyridylmethyl	4-MeOC 6 H 4
149	4-pyridylmethyl	3-MeOC 6 H 4
150	4-pyridylmethyl	4-NH 2 C 6 H 4
151	4-pyridylmethyl	3-NH 2 C 6 H 4
152	4-pyridylmethyl	2-NH 2 C 6 H 4
153	4-pyridylmethyl	4-Me 2 NC 6 H 4
154	4-pyridylmethyl	3-Me 2 NC 6 H 4
155	4-pyridylmethyl	2-Me 2 NC 6 H 4
156	4-pyridylmethyl	4-pyridyl
157	4-pyridylmethyl	3-pyridyl
158	4-pyridylmethyl	2-pyridyl
159	4-pyridylmethyl	2-thiazolyl
160	4-pyridylmethyl	2-pyrazolyl
161	4-pyridylmethyl	5-isoquinolyl
162	4-pyridylmethyl	3,4-methylenedioxyC 6 H 3
163	4-pyridylmethyl	3,4-ethylenedioxyC 6 H 3
164	4-pyridylmethyl	2-imidazolyl
165	4-pyridylmethyl	2-oxazolyl
166	4-pyridylmethyl	4-isoxazolyl
167	4-pyridylmethyl	4-HOC 6 H 4
168	4-pyridylmethyl	3-HOC 6 H 4
169	4-pyridylmethyl	3,4-diHOC 6 H 4
170	4-pyridylmethyl	4-NH 2 CH 2 C 6 H 4
171	4-pyridylmethyl	3-NH 2 CH 2 C 6 H 4
172	2-NH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
173	2-NH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
174	2-NH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
175	2-NH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
176	2-NH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
177	2-NH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
178	2-NH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
179	2-NH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
180	2-NH 2 C 6 H 4 CH 2	4-pyridyl
181	2-NH 2 C 6 H 4 CH 2	3-pyridyl
182	2-NH 2 C 6 H 4 CH 2	2-pyridyl
183	2-NH 2 C 6 H 4 CH 2	2-thiazolyl
184	2-NH 2 C 6 H 4 CH 2	2-pyrazolyl
185	2-NH 2 C 6 H 4 CH 2	5-isoquinolyl
186	2-NH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
187	2-NH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
188	2-NH 2 C 6 H 4 CH 2	2-imidazolyl
189	2-NH 2 C 6 H 4 CH 2	2-oxazolyl
190	2-NH 2 C 6 H 4 CH 2	4-isoxazolyl
191	2-NH 2 C 6 H 4 CH 2	4-HOC 6 H 4
192	2-NH 2 C 6 H 4 CH 2	3-HOC 6 H 4
193	2-NH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
194	2-NH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
195	2-NH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
196	3-NH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
197	3-NH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
198	3-NH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
199	3-NH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
200	3-NH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
201	3-NH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
202	3-NH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
203	3-NH 2 C 6 H 4 CH 2	4-pyridyl
204	3-NH 2 C 6 H 4 CH 2	3-pyridyl
205	3-NH 2 C 6 H 4 CH 2	2-pyridyl
206	3-NH 2 C 6 H 4 CH 2	2-thiazolyl
207	3-NH 2 C 6 H 4 CH 2	2-pyrazolyl
208	3-NH 2 C 6 H 4 CH 2	5-isoquinolyl
209	3-NH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
210	3-NH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
211	3-NH 2 C 6 H 4 CH 2	2-imidazolyl
212	3-NH 2 C 6 H 4 CH 2	2-oxazolyl
213	3-NH 2 C 6 H 4 CH 2	4-isoxazolyl
214	3-NH 2 C 6 H 4 CH 2	4-HOC 6 H 4
215	3-NH 2 C 6 H 4 CH 2	3-HOC 6 H 4
216	3-NH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
217	3-NH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
218	3-NH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
219	4-NH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
220	4-NH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
221	4-NH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
222	4-NH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
223	4-NH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
224	4-NH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
225	4-NH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
226	4-NH 2 C 6 H 4 CH 2	4-pyridyl
227	4-NH 2 C 6 H 4 CH 2	3-pyridyl
228	4-NH 2 C 6 H 4 CH 2	2-pyridyl
229	4-NH 2 C 6 H 4 CH 2	2-thiazolyl
230	4-NH 2 C 6 H 4 CH 2	2-pyrazolyl
231	4-NH 2 C 6 H 4 CH 2	5-isoquinolyl
232	4-NH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
233	4-NH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
234	4-NH 2 C 6 H 4 CH 2	2-imidazolyl
235	4-NH 2 C 6 H 4 CH 2	2-oxazolyl
236	4-NH 2 C 6 H 4 CH 2	4-isoxazolyl
237	4-NH 2 C 6 H 4 CH 2	4-HOC 6 H 4
238	4-NH 2 C 6 H 4 CH 2	3-HOC 6 H 4
239	4-NH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
240	4-NH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
241	4-NH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
242	2-MeOC 6 H 4 CH 2	3-MeOC 6 H 4
243	2-MeOC 6 H 4 CH 2	4-NH 2 C 6 H 4
244	2-MeOC 6 H 4 CH 2	3-NH 2 C 6 H 4
245	2-MeOC 6 H 4 CH 2	2-NH 2 C 6 H 4
246	2-MeOC 6 H 4 CH 2	4-Me 2 NC 6 H 4
247	2-MeOC 6 H 4 CH 2	3-Me 2 NC 6 H 4
248	2-MeOC 6 H 4 CH 2	2-Me 2 NC 6 H 4
249	2-MeOC 6 H 4 CH 2	4-pyridyl
250	2-MeOC 6 H 4 CH 2	3-pyridyl
251	2-MeOC 6 H 4 CH 2	2-pyridyl
252	2-MeOC 6 H 4 CH 2	2-thiazolyl
253	2-MeOC 6 H 4 CH 2	2-pyrazolyl
254	2-MeOC 6 H 4 CH 2	5-isoquinolyl
255	2-MeOC 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
256	2-MeOC 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
257	2-MeOC 6 H 4 CH 2	2-imidazolyl
258	2-MeOC 6 H 4 CH 2	2-oxazolyl
259	2-MeOC 6 H 4 CH 2	4-isoxazolyl
260	2-MeOC 6 H 4 CH 2	4-HOC 6 H 4
261	2-MeOC 6 H 4 CH 2	3-HOC 6 H 4
262	2-MeOC 6 H 4 CH 2	3,4-diHOC 6 H 4
263	2-MeOC 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
264	2-MeOC 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
265	3-MeOC 6 H 4 CH 2	3-MeOC 6 H 4
266	3-MeOC 6 H 4 CH 2	4-NH 2 C 6 H 4
267	3-MeOC 6 H 4 CH 2	3-NH 2 C 6 H 4
268	3-MeOC 6 H 4 CH 2	2-NH 2 C 6 H 4
269	3-MeOC 6 H 4 CH 2	4-Me 2 NC 6 H 4
270	3-MeOC 6 H 4 CH 2	3-Me 2 NC 6 H 4
271	3-MeOC 6 H 4 CH 2	2-Me 2 NC 6 H 4
272	3-MeOC 6 H 4 CH 2	4-pyridyl
273	3-MeOC 6 H 4 CH 2	3-pyridyl
274	3-MeOC 6 H 4 CH 2	2-pyridyl
275	3-MeOC 6 H 4 CH 2	2-thiazolyl
276	3-MeOC 6 H 4 CH 2	2-pyrazolyl
277	3-MeOC 6 H 4 CH 2	5-isoquinolyl
278	3-MeOC 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
279	3-MeOC 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
280	3-MeOC 6 H 4 CH 2	2-imidazolyl
281	3-MeOC 6 H 4 CH 2	2-oxazolyl
282	3-MeOC 6 H 4 CH 2	4-isoxazolyl
283	3-MeOC 6 H 4 CH 2	4-HOC 6 H 4
284	3-MeOC 6 H 4 CH 2	3-HOC 6 H 4
285	3-MeOC 6 H 4 CH 2	3,4-diHOC 6 H 4
286	3-MeOC 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
287	3-MeOC 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
288	4-MeOC 6 H 4 CH 2	3-MeOC 6 H 4
289	4-MeOC 6 H 4 CH 2	4-NH 2 C 6 H 4
290	4-MeOC 6 H 4 CH 2	3-NH 2 C 6 H 4
291	4-MeOC 6 H 4 CH 2	2-NH 2 C 6 H 4
292	4-MeOC 6 H 4 CH 2	4-Me 2 NC 6 H 4
293	4-MeOC 6 H 4 CH 2	3-Me 2 NC 6 H 4
294	4-MeOC 6 H 4 CH 2	2-Me 2 NC 6 H 4
295	4-MeOC 6 H 4 CH 2	4-pyridyl
296	4-MeOC 6 H 4 CH 2	3-pyridyl
297	4-MeOC 6 H 4 CH 2	2-pyridyl
298	4-MeOC 6 H 4 CH 2	2-thiazolyl
299	4-MeOC 6 H 4 CH 2	2-pyrazolyl
300	4-MeOC 6 H 4 CH 2	5-isoquinolyl
301	4-MeOC 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
302	4-MeOC 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
303	4-MeOC 6 H 4 CH 2	2-imidazolyl
304	4-MeOC 6 H 4CH 2	2-oxazolyl
305	4-MeOC 6 H 4 CH 2	4-isoxazolyl
306	4-MeOC 6 H 4 CH 2	4-HOC 6 H 4
307	4-MeOC 6 H 4 CH 2	3-HOC 6 H 4
308	4-MeOC 6 H 4 CH 2	3,4-diHOC 6 H 4
309	4-MeOC 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
310	4-MeOC 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
311	2-HOC 6 H 4 CH 2	4-MeOC 6 H 4
312	2-HOC 6 H 4 CH 2	3-MeOC 6 H 4
313	2-HOC 6 H 4 CH 2	4-NH 2 C 6 H 4
314	2-HOC 6 H 4 CH 2	3-NH 2 C 6 H 4
315	2-HOC 6 H 4 CH 2	2-NH 2 C 6 H 4
316	2-HOC 6 H 4 CH 2	4-Me 2 NC 6 H 4
317	2-HOC 6 H 4 CH 2	3-Me 2 NC 6 H 4
318	2-HOC 6 H 4 CH 2	2-Me 2 NC 6 H 4
319	2-HOC 6 H 4 CH 2	4-pyridyl
320	2-HOC 6 H 4 CH 2	3-pyridyl
321	2-HOC 6 H 4 CH 2	2-pyridyl
322	2-HOC 6 H 4 CH 2	2-thiazolyl
323	2-HOC 6 H 4 CH 2	2-pyrazolyl
324	2-HOC 6 H 4 CH 2	5-isoquinolyl
325	2-HOC 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
326	2-HOC 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
327	2-HOC 6 H 4 CH 2	2-imidazolyl
328	2-HOC 6 H 4 CH 2	2-oxazolyl
329	2-HOC 6 H 4 CH 2	4-isoxazolyl
330	2-HOC 6 H 4 CH 2	4-HOC 6 H 4
331	2-HOC 6 H 4 CH 2	3-HOC 6 H 4
332	2-HOC 6 H 4 CH 2	3,4-diHOC 6 H 4
333	2-HOC 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
334	2-HOC 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
335	3-HOC 6 H 4 CH 2	4-MeOC 6 H 4
336	3-HOC 6 H 4 CH 2	3-MeOC 6 H 4
337	3-HOC 6 H 4 CH 2	4-NH 2 C 6 H 4
338	3-HOC 6 H 4 CH 2	3-NH 2 C 6 H 4
339	3-HOC 6 H 4 CH 2	2-NH 2 C 6 H 4
340	3-HOC 6 H 4 CH 2	4-Me 2 NC 6 H 4
341	3-HOC 6 H 4 CH 2	3-Me 2 NC 6 H 4
342	3-HOC 6 H 4 CH 2	2-Me 2 NC 6 H 4
343	3-HOC 6 H 4 CH 2	4-pyridyl
344	3-HOC 6 H 4 CH 2	3-pyridyl
345	3-HOC 6 H 4 CH 2	2-pyridyl
346	3-HOC 6 H 4 CH 2	2-thiazolyl
347	3-HOC 6 H 4 CH 2	2-pyrazolyl
348	3-HOC 6 H 4 CH 2	5-isoquinolyl
349	3-HOC 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
350	3-HOC 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
351	3-HOC 6 H 4 CH 2	2-imidazolyl
352	3-HOC 6 H 4 CH 2	2-oxazolyl
353	3-HOC 6 H 4 CH 2	4-isoxazolyl
354	3-HOC 6 H 4 CH 2	4-HOC 6 H 4
355	3-HOC 6 H 4 CH 2	3-HOC 6 H 4
356	3-HOC 6 H 4 CH 2	3,4-diHOC 6 H 4
357	3-HOC 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
358	3-HOC 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
359	4-HOC 6 H 4 CH 2	4-MeOC 6 H 4
360	4-HOC 6 H 4 CH 2	3-MeOC 6 H 4
361	4-HOC 6 H 4 CH 2	4-NH 2 C 6 H 4
362	4-HOC 6 H 4 CH 2	3-NH 2 C 6 H 4
363	4-HOC 6 H 4 CH 2	2-NH 2 C 6 H 4
364	4-HOC 6 H 4 CH 2	4-Me 2 NC 6 H 4
365	4-HOC 6 H 4 CH 2	3-Me 2 NC 6 H 4
366	4-HOC 6 H 4 CH 2	2-Me 2 NC 6 H 4
367	4-HOC 6 H 4 CH 2	4-pyridyl
368	4-HOC 6 H 4 CH 2	3-pyridyl
369	4-HOC 6 H 4 CH 2	2-pyridyl
370	4-HOC 6 H 4 CH 2	2-thiazolyl
371	4-HOC 6 H 4 CH 2	2-pyrazolyl
372	4-HOC 6 H 4 CH 2	5-isoquinolyl
373	4-HOC 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
374	4-HOC 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
375	4-HOC 6 H 4 CH 2	2-imidazolyl
376	4-HOC 6 H 4 CH 2	2-oxazolyl
377	4-HOC 6 H 4 CH 2	4-isoxazolyl
378	4-HOC 6 H 4 CH 2	4-HOC 6 H 4
379	4-HOC 6 H 4 CH 2	3-HOC 6 H 4
380	4-HOC 6 H 4 CH 2	3,4-diHOC 6 H 4
381	4-HOC 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
382	4-HOC 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
383	4-ClC 6 H 4 CH 2	3-MeOC 6 H 4
384	4-ClC 6 H 4 CH 2	4-NH 2 C 6 H 4
385	4-ClC 6 H 4 CH 2	3-NH 2 C 6 H 4
386	4-ClC 6 H 4 CH 2	2-NH 2 C 6 H 4
387	4-ClC 6 H 4 CH 2	4-Me 2 NC 6 H 4
388	4-ClC 6 H 4 CH 2	3-Me 2 NC 6 H 4
389	4-ClC 6 H 4 CH 2	2-Me 2 NC 6 H 4
390	4-ClC 6 H 4 CH 2	4-pyridyl
391	4-ClC 6 H 4 CH 2	3-pyridyl
392	4-ClC 6 H 4 CH 2	2-pyridyl
393	4-ClC 6 H 4 CH 2	2-thiazolyl
394	4-ClC 6 H 4 CH 2	2-pyrazolyl
395	4-ClC 6 H 4 CH 2	5-isoquinolyl
396	4-ClC 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
397	4-ClC 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
398	4-ClC 6 H 4 CH 2	2-imidazolyl
399	4-ClC 6 H 4 CH 2	2-oxazolyl
400	4-ClC 6 H 4 CH 2	4-isoxazolyl
401	4-ClC 6 H 4 CH 2	4-HOC 6 H 4
402	4-ClC 6 H 4 CH 2	3-HOC 6 H 4
403	4-ClC 6 H 4 CH 2	3,4-diHOC 6 H 4
404	4-ClC 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
405	4-ClC 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
406	2-NH 2 CH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
407	2-NH 2 CH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
408	2-NH 2 CH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
409	2-NH 2 CH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
410	2-NH 2 CH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
411	2-NH 2 CH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
412	2-NH 2 CH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
413	2-NH 2 CH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
414	2-NH 2 CH 2 C 6 H 4 CH 2	4-pyridyl
415	2-NH 2 CH 2 C 6 H 4 CH 2	3-pyridyl
416	2-NH 2 CH 2 C 6 H 4 CH 2	2-pyridyl
417	2-NH 2 CH 2 C 6 H 4 CH 2	2-thiazolyl
418	2-NH 2 CH 2 C 6 H 4 CH 2	2-pyrazolyl
419	2-NH 2 CH 2 C 6 H 4 CH 2	5-isoquinolyl
420	2-NH 2 CH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
421	2-NH 2 CH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
422	2-NH 2 CH 2 C 6 H 4 CH 2	2-imidazolyl
423	2-NH 2 CH 2 C 6 H 4 CH 2	2-oxazolyl
424	2-NH 2 CH 2 C 6 H 4 CH 2	4-isoxazolyl
425	2-NH 2 CH 2 C 6 H 4 CH 2	4-HOC 6 H 4
426	2-NH 2 CH 2 C 6 H 4 CH 2	3-HOC 6 H 4
427	2-NH 2 CH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
428	2-NH 2 CH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
429	2-NH 2 CH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
430	3-NH 2 CH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
431	3-NH 2 CH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
432	3-NH 2 CH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
433	3-NH 2 CH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
434	3-NH 2 CH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
435	3-NH 2 CH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
436	3-NH 2 CH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
437	3-NH 2 CH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
438	3-NH 2 CH 2 C 6 H 4 CH 2	4-pyridyl
439	3-NH 2 CH 2 C 6 H 4 CH 2	3-pyridyl
440	3-NH 2 CH 2 C 6 H 4 CH 2	2-pyridyl
441	3-NH 2 CH 2 C 6 H 4 CH 2	2-thiazolyl
442	3-NH 2 CH 2 C 6 H 4 CH 2	2-pyrazolyl
443	3-NH 2 CH 2 C 6 H 4 CH 2	5-isoquinolyl
444	3-NH 2 CH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
445	3-NH 2 CH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
446	3-NH 2 CH 2 C 6 H 4 CH 2	2-imidazolyl
447	3-NH 2 CH 2 C 6 H 4 CH 2	2-oxazolyl
448	3-NH 2 CH 2 C 6 H 4 CH 2	4-isoxazolyl
449	3-NH 2 CH 2 C 6 H 4 CH 2	4-HOC 6 H 4
450	3-NH 2 CH 2 C 6 H 4 CH 2	3-HOC 6 H 4
451	3-NH 2 CH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
452	3-NH 2 CH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
453	3-NH 2 CH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
454	4-NH 2 CH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
455	4-NH 2 CH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
456	4-NH 2 CH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
457	4-NH 2 CH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
458	4-NH 2 CH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
459	4-NH 2 CH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
460	4-NH 2 CH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
461	4-NH 2 CH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
462	4-NH 2 CH 2 C 6 H 4 CH 2	4-pyridyl
463	4-NH 2 CH 2 C 6 H 4 CH 2	3-pyridyl
464	4-NH 2 CH 2 C 6 H 4 CH 2	2-pyridyl
465	4-NH 2 CH 2 C 6 H 4 CH 2	2-thiazolyl
466	4-NH 2 CH 2 C 6 H 4 CH 2	2-pyrazolyl
467	4-NH 2 CH 2 C 6 H 4 CH 2	5-isoquinolyl
468	4-NH 2 CH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
469	4-NH 2 CH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
470	4-NH 2 CH 2 C 6 H 4 CH 2	2-imidazolyl
471	4-NH 2 CH 2 C 6 H 4 CH 2	2-oxazolyl
472	4-NH 2 CH 2 C 6 H 4 CH 2	4-isoxazolyl
473	4-NH 2 CH 2 C 6 H 4 CH 2	4-HOC 6 H 4
474	4-NH 2 CH 2 C 6 H 4 CH 2	3-HOC 6 H 4
475	4-NH 2 CH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
476	4-NH 2 CH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
477	4-NH 2 CH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
478	2-Me 2 NCH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
479	2-Me 2 NCH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
480	2-Me 2 NCH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
481	2-Me 2 NCH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
482	2-Me 2 NCH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
483	2-Me 2 NCH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
484	2-Me 2 NCH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
485	2-Me 2 NCH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
486	2-Me 2 NCH 2 C 6 H 4 CH 2	4-pyridyl
487	2-Me 2 NCH 2 C 6 H 4 CH 2	3-pyridyl
488	2-Me 2 NCH 2 C 6 H 4 CH 2	2-pyridyl
489	2-Me 2 NCH 2 C 6 H 4 CH 2	2-thiazolyl
490	2-Me 2 NCH 2 C 6 H 4 CH 2	2-pyrazolyl
491	2-Me 2 NCH 2 C 6 H 4 CH 2	5-isoquinolyl
492	2-Me 2 NCH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
493	2-Me 2 NCH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
494	2-Me 2 NCH 2 C 6 H 4 CH 2	2-imidazolyl
495	2-Me 2 NCH 2 C 6 H 4 CH 2	2-oxazolyl
496	2-Me 2 NCH 2 C 6 H 4 CH 2	4-isoxazolyl
497	2-Me 2 NCH 2 C 6 H 4 CH 2	4-HOC 6 H 4
498	2-Me 2 NCH 2 C 6 H 4 CH 2	3-HOC 6 H 4
499	2-Me 2 NCH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
500	2-Me 2 NCH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
501	2-Me 2 NCH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
502	3-Me 2 NCH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
503	3-Me 2 NCH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
504	3-Me 2 NCH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
505	3-Me 2 NCH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
506	3-Me 2 NCH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
507	3-Me 2 NCH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
508	3-Me 2 NCH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
509	3-Me 2 NCH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
510	3-Me 2 NCH 2 C 6 H 4 CH 2	4-pyridyl
511	3-Me 2 NCH 2 C 6 H 4 CH 2	3-pyridyl
512	3-Me 2 NCH 2 C 6 H 4 CH 2	2-pyridyl
513	3-Me 2 NCH 2 C 6 H 4 CH 2	2-thiazolyl
514	3-Me 2 NCH 2 C 6 H 4 CH 2	2-pyrazolyl
515	3-Me 2 NCH 2 C 6 H 4 CH 2	5-isoquinolyl
516	3-Me 2 NCH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
517	3-Me 2 NCH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
518	3-Me 2 NCH 2 C 6 H 4 CH 2	2-imidazolyl
519	3-Me 2 NCH 2 C 6 H 4 CH 2	2-oxazolyl
520	3-Me 2 NCH 2 C 6 H 4 CH 2	4-isoxazolyl
521	3-Me 2 NCH 2 C 6 H 4 CH 2	4-HOC 6 H 4
522	3-Me 2 NCH 2 C 6 H 4 CH 2	3-HOC 6 H 4
523	3-Me 2 NCH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
524	3-Me 2 NCH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
525	3-Me 2 NCH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
526	4-Me 2 NCH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
527	4-Me 2 NCH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
528	4-Me 2 NCH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
529	4-Me 2 NCH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
530	4-Me 2 NCH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
531	4-Me 2 NCH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
532	4-Me 2 NCH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
533	4-Me 2 NCH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
534	4-Me 2 NCH 2 C 6 H 4 CH 2	4-pyridyl
535	4-Me 2 NCH 2 C 6 H 4 CH 2	3-pyridyl
536	4-Me 2 NCH 2 C 6 H 4 CH 2	2-pyridyl
537	4-Me 2 NCH 2 C 6 H 4 CH 2	2-thiazolyl
538	4-Me 2 NCH 2 C 6 H 4 CH 2	2-pyrazolyl
539	4-Me 2 NCH 2 C 6 H 4 CH 2	5-isoquinolyl
540	4-Me 2 NCH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
541	4-Me 2 NCH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
542	4-Me 2 NCH 2 C 6 H 4 CH 2	2-imidazolyl
543	4-Me 2 NCH 2 C 6 H 4 CH 2	2-oxazolyl
545	4-Me 2 NCH 2 C 6 H 4 CH 2	4-isoxazolyl
546	4-Me 2 NCH 2 C 6 H 4 CH 2	4-HOC 6 H 4
547	4-Me 2 NCH 2 C 6 H 4 CH 2	3-HOC 6 H 4
548	4-Me 2 NCH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
549	4-Me 2 NCH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
550	4-Me 2 NCH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
551	H	3-MeOC 6 H 4
552	H	4-NH 2 C 6 H 4
553	H	3-NH 2 C 6 H 4
554	H	2-NH 2 C 6 H 4
555	H	4-Me 2 NC 6 H 4
556	H	3-Me 2 NC 6 H 4
557	H	2-Me 2 NC 6 H 4
558	H	3-pyridyl
559	H	2-pyridyl
560	H	2-thiazolyl
561	H	2-pyrazolyl
562	H	5-isoquinolyl
563	H	3,4-methylenedioxyC 6 H 3
564	H	3,4-ethylenedioxyC 6 H 3
565	H	2-imidazolyl
566	H	2-oxazolyl
567	H	4-isoxazolyl
568	H	4-HOC 6 H 4
569	H	3-HOC 6 H 4
570	H	3,4-diHOC 6 H 4
571	H	4-NH 2 CH 2 C 6 H 4
572	H	3-NH 2 CH 2 C 6 H 4
573	Me	3-MeOC 6 H 4
574	Me	4-NH 2 C 6 H 4
575	Me	3-NH 2 C 6 H 4
576	Me	2-NH 2 C 6 H 4
577	Me	4-Me 2 NC 6 H 4
578	Me	3-Me 2 NC 6 H 4
579	Me	2-Me 2 NC 6 H 4
580	Me	3-pyridyl
581	Me	2-pyridyl
582	Me	2-thiazolyl
583	Me	2-pyrazolyl
584	Me	5-isoquinolyl
585	Me	3,4-ethylenedioxyC 6 H 3
586	Me	2-imidazolyl
587	Me	2-oxazolyl
588	Me	4-isoxazolyl
589	Me	3-HOC 6 H 4
590	Me	3,4-diHOC 6 H 4
591	Me	4-NH 2 CH 2 C 6 H 4
592	Me	3-NH 2 CH 2 C 6 H 4
593	Et	3-MeOC 6 H 4
594	Et	4-NH 2 C 6 H 4
595	Et	3-NH 2 C 6 H 4
596	Et	2-NH 2 C 6 H 4
597	Et	4-Me 2 NC 6 H 4
598	Et	3-Me 2 NC 6 H 4
599	Et	2-Me 2 NC 6 H 4
600	Et	4-pyridyl
601	Et	3-pyridyl
602	Et	2-pyridyl
603	Et	2-thiazolyl
604	Et	2-pyrazolyl
605	Et	5-isoquinolyl
606	Et	3,4-methylenedioxyC 6 H 3
607	Et	3,4-ethylenedioxyC 6 H 3
608	Et	2-imidazolyl
609	Et	2-oxazolyl
610	Et	4-isoxazolyl
611	Et	4-HOC 6 H 4
612	Et	3-HOC 6 H 4
613	Et	3,4-diHOC 6 H 4
614	Et	4-NH 2 CH 2 C 6 H 4
615	Et	3-NH 2 CH 2 C 6 H 4
616	Me 2 NCH 2	3-MeOC 6 H 4
617	Me 2 NCH 2	4-NH 2 C 6 H 4
618	Me 2 NCH 2	3-NH 2 C 6 H 4
619	Me 2 NCH 2	2-NH 2 C 6 H 4
620	Me 2 NCH 2	4-Me 2 NC 6 H 4
621	Me 2 NCH 2	3-Me 2 NC 6 H 4
622	Me 2 NCH 2	2-Me 2 NC 6 H 4
623	Me 2 NCH 2	4-pyridyl
624	Me 2 NCH 2	3-pyridyl
625	Me 2 NCH 2	2-pyridyl
626	Me 2 NCH 2	2-thiazolyl
627	Me 2 NCH 2	2-pyrazolyl
628	Me 2 NCH 2	5-isoquinolyl
629	Me 2 NCH 2	3,4-methylenedioxyC 6 H 3
630	Me 2 NCH 2	3,4-ethylenedioxyC 6 H 3
631	Me 2 NCH 2	2-imidazolyl
632	Me 2 NCH 2	2-oxazolyl
633	Me 2 NCH 2	4-isoxazolyl
634	Me 2 NCH 2	4-HOC 6 H 4
635	Me 2 NCH 2	3-HOC 6 H 4
636	Me 2 NCH 2	3,4-diHOC 6 H 4
637	Me 2 NCH 2	4-NH 2 CH 2 C 6 H 4
638	Me 2 NCH 2	3-NH 2 CH 2 C 6 H 4
639	EtNHCH 2	3-MeOC 6 H 4
640	EtNHCH 2	4-NH 2 C 6 H 4
641	EtNHCH 2	3-NH 2 C 6 H 4
642	EtNHCH 2	2-NH 2 C 6 H 4
643	EtNHCH 2	4-Me 2 NC 6 H 4
644	EtNHCH 2	3-Me 2 NC 6 H 4
645	EtNHCH 2	2-Me 2 NC 6 H 4
646	EtNHCH 2	4-pyridyl
647	EtNHCH 2	3-pyridyl
648	EtNHCH 2	2-pyridyl
649	EtNHCH 2	2-thiazolyl
650	EtNHCH 2	2-pyrazolyl
651	EtNHCH 2	5-isoquinolyl
652	EtNHCH 2	3,4-methylenedioxyC 6 H 3
653	EtNHCH 2	3,4-ethylenedioxyC 6 H 3
654	EtNHCH 2	2-imidazolyl
655	EtNHCH 2	2-oxazolyl
656	EtNHCH 2	4-isoxazolyl
657	EtNHCH 2	4-HOC 6 H 4
658	EtNHCH 2	3-HOC 6 H 4
659	EtNHCH 2	3,4-diHOC 6 H 4
660	EtNHCH 2	4-NH 2 CH 2 C 6 H 4
661	EtNHCH 2	3-NH 2 CH 2 C 6 H 4
662	HOCH 2 CH 2 NHCH 2	3-MeOC 6 H 4
663	HOCH 2 CH 2 NHCH 2	4-NH 2 C 6 H 4
664	HOCH 2 CH 2 NHCH 2	3-NH 2 C 6 H 4
665	HOCH 2 CH 2 NHCH 2	2-NH 2 C 6 H 4
666	HOCH 2 CH 2 NHCH 2	4-Me 2 NC 6 H 4
667	HOCH 2 CH 2 NHCH 2	3-Me 2 NC 6 H 4
668	HOCH 2 CH 2 NHCH 2	2-Me 2 NC 6 H 4
669	HOCH 2 CH 2 NHCH 2	4-pyridyl
670	HOCH 2 CH 2 NHCH 2	3-pyridyl
671	HOCH 2 CH 2 NHCH 2	2-pyridyl
672	HOCH 2 CH 2 NHCH 2	2-thiazolyl
673	HOCH 2 CH 2 NHCH 2	2-pyrazolyl
674	HOCH 2 CH 2 NHCH 2	5-isoquinolyl
675	HOCH 2 CH 2 NHCH 2	3,4-methylenedioxyC 6 H 3
676	HOCH 2 CH 2 NHCH 2	3,4-ethylenedioxyC 6 H 3
677	HOCH 2 CH 2 NHCH 2	2-imidazolyl
678	HOCH 2 CH 2 NHCH 2	2-oxazolyl
679	HOCH 2 CH 2 NHCH 2	4-isoxazolyl
680	HOCH 2 CH 2 NHCH 2	4-HOC 6 H 4
681	HOCH 2 CH 2 NHCH 2	3-HOC 6 H 4
682	HOCH 2 CH 2 NHCH 2	3,4-diHOC 6 H 4
683	HOCH 2 CH 2 NHCH 2	4-NH 2 CH 2 C 6 H 4
684	HOCH 2 CH 2 NHCH 2	3-NH 2 CH 2 C 6 H 4
685	H 2 NCH 2 CH 2 NHCH 2	4-MeOC 6 H 4
686	H 2 NCH 2 CH 2 NHCH 2	3-MeOC 6 H 4
687	H 2 NCH 2 CH 2 NHCH 2	4-NH 2 C 6 H 4
688	H 2 NCH 2 CH 2 NHCH 2	3-NH 2 C 6 H 4
689	H 2 NCH 2 CH 2 NHCH 2	2-NH 2 C 6 H 4
690	H 2 NCH 2 CH 2 NHCH 2	4-Me 2 NC 6 H 4
691	H 2 NCH 2 CH 2 NHCH 2	3-Me 2 NC 6 H 4
692	H 2 NCH 2 CH 2 NHCH 2	2-Me 2 NC 6 H 4
693	H 2 NCH 2 CH 2 NHCH 2	4-pyridyl
694	H 2 NCH 2 CH 2 NHCH 2	3-pyridyl
695	H 2 NCH 2 CH 2 NHCH 2	2-pyridyl
696	H 2 NCH 2 CH 2 NHCH 2	2-thiazolyl
697	H 2 NCH 2 CH 2 NHCH 2	2-pyrazolyl
698	H 2 NCH 2 CH 2 NHCH 2	5-isoquinolyl
699	H 2 NCH 2 CH 2 NHCH 2	3,4-methylenedioxyC 6 H 3
700	H 2 NCH 2 CH 2 NHCH 2	3,4-ethylenedioxyC 6 H 3
701	H 2 NCH 2 CH 2 NHCH 2	2-imidazolyl
702	H 2 NCH 2 CH 2 NHCH 2	2-oxazolyl
703	H 2 NCH 2 CH 2 NHCH 2	4-isoxazolyl
704	H 2 NCH 2 CH 2 NHCH 2	4-HOC 6 H 4
705	H 2 NCH 2 CH 2 NHCH 2	3-HOC 6 H 4
706	H 2 NCH 2 CH 2 NHCH 2	3,4-diHOC 6 H 4
707	H 2 NCH 2 CH 2 NHCH 2	4-NH 2 CH 2 C 6 H 4
708	H 2 NCH 2 CH 2 NHCH 2	3-NH 2 CH 2 C 6 H 4
709	Me 2 NCH 2 CH 2 NHCH 2	4-MeOC 6 H 4
710	Me 2 NCH 2 CH 2 NHCH 2	3-MeOC 6 H 4
711	Me 2 NCH 2 CH 2 NHCH 2	4-NH 2 C 6 H 4
712	Me 2 NCH 2 CH 2 NHCH 2	3-NH 2 C 6 H 4
713	Me 2 NCH 2 CH 2 NHCH 2	2-NH 2 C 6 H 4
714	Me 2 NCH 2 CH 2 NHCH 2	4-Me 2 NC 6 H 4
715	Me 2 NCH 2 CH 2 NHCH 2	3-Me 2 NC 6 H 4
716	Me 2 NCH 2 CH 2 NHCH 2	2-Me 2 NC 6 H 4
717	Me 2 NCH 2 CH 2 NHCH 2	4-pyridyl
718	Me 2 NCH 2 CH 2 NHCH 2	3-pyridyl
719	Me 2 NCH 2 CH 2 NHCH 2	2-pyridyl
720	Me 2 NCH 2 CH 2 NHCH 2	2-thiazolyl
721	Me 2 NCH 2 CH 2 NHCH 2	2-pyrazolyl
722	Me 2 NCH 2 CH 2 NHCH 2	5-isoquinolyl
723	Me 2 NCH 2 CH 2 NHCH 2	3,4-methylenedioxyC 6 H 3
724	Me 2 NCH 2 CH 2 NHCH 2	3,4-ethylenedioxyC 6 H 3
725	Me 2 NCH 2 CH 2 NHCH 2	2-imidazolyl
726	Me 2 NCH 2 CH 2 NHCH 2	2-oxazolyl
727	Me 2 NCH 2 CH 2 NHCH 2	4-isoxazolyl
728	Me 2 NCH 2 CH 2 NHCH 2	4-HOC 6 H 4
729	Me 2 NCH 2 CH 2 NHCH 2	3-HOC 6 H 4
730	Me 2 NCH 2 CH 2 NHCH 2	3,4-diHOC 6 H 4
731	Me 2 NCH 2 CH 2 NHCH 2	4-NH 2 CH 2 C 6 H 4
732	Me 2 NCH 2 CH 2 NHCH 2	3-NH 2 CH 2 C 6 H 4
733	1-morpholinylmethyl	3-MeOC 6 H 4
734	1-morpholinylmethyl	4-NH 2 C 6 H 4
735	1-morpholinylmethyl	3-NH 2 C 6 H 4
736	1-morpholinylmethyl	2-NH 2 C 6 H 4
737	1-morpholinylmethyl	4-Me 2 NC 6 H 4
738	1-morpholinylmethyl	3-Me 2 NC 6 H 4
739	1-morpholinylmethyl	2-Me 2 NC 6 H 4
740	1-morpholinylmethyl	4-pyridyl
741	1-morpholinylmethyl	3-pyridyl
742	1-morpholinylmethyl	2-pyridyl
743	1-morpholinylmethyl	2-thiazolyl
744	1-morpholinylmethyl	2-pyrazolyl
745	1-morpholinylmethyl	5-isoquinolyl
746	1-morpholinylmethyl	3,4-methylenedioxyC 6 H 3
747	1-morpholinylmethyl	3,4-ethylenedioxyC 6 H 3
748	1-morpholinylmethyl	2-imidazolyl
749	1-morpholinylmethyl	2-oxazolyl
750	1-morpholinylmethyl	4-isoxazolyl
751	1-morpholinylmethyl	4-HOC 6 H 4
752	1-morpholinylmethyl	3-HOC 6 H 4
753	1-morpholinylmethyl	3,4-diHOC 6 H 4
754	1-morpholinylmethyl	4-NH 2 CH 2 C 6 H 4
755	1-morpholinylmethyl	3-NH 2 CH 2 C 6 H 4
756	1-thiomorpholinylmethyl	3-MeOC 6 H 4
757	1-thiomorpholinylmethyl	4-NH 2 C 6 H 4
758	1-thiomorpholinylmethyl	3-NH 2 C 6 H 4
759	1-thiomorpholinylmethyl	2-NH 2 C 6 H 4
760	1-thiomorpholinylmethyl	4-Me 2 NC 6 H 4
761	1-thiomorpholinylmethyl	3-Me 2 NC 6 H 4
762	1-thiomorpholinylmethyl	2-Me 2 NC 6 H 4
763	1-thiomorpholinylmethyl	4-pyridyl
764	1-thiomorpholinylmethyl	3-pyridyl
765	1-thiomorpholinylmethyl	2-pyridyl
766	1-thiomorpholinylmethyl	2-thiazolyl
767	1-thiomorpholinylmethyl	2-pyrazolyl
768	1-thiomorpholinylmethyl	5-isoquinolyl
769	1-thiomorpholinylmethyl	3,4-methylenedioxyC 6 H 3
770	1-thiomorpholinylmethyl	3,4-ethylenedioxyC 6 H 3
771	1-thiomorpholinylmethyl	2-imidazolyl
772	1-thiomorpholinylmethyl	2-oxazolyl
773	1-thiomorpholinylmethyl	4-isoxazolyl
774	1-thiomorpholinylmethyl	4-HOC 6 H 4
775	1-thiomorpholinylmethyl	3-HOC 6 H 4
776	1-thiomorpholinylmethyl	3,4-diHOC 6 H 4
777	1-thiomorpholinylmethyl	4-NH 2 CH 2 C 6 H 4
778	1-thiomorpholinylmethyl	3-NH 2 CH 2 C 6 H 4
779	1-piperazinylmethyl	3-MeOC 6 H 4
780	1-piperazinylmethyl	4-NH 2 C 6 H 4
781	1-piperazinylmethyl	3-NH 2 C 6 H 4
782	1-piperazinylmethyl	2-NH 2 C 6 H 4
783	1-piperazinylmethyl	4-Me 2 NC 6 H 4
784	1-piperazinylmethyl	3-Me 2 NC 6 H 4
785	1-piperazinylmethyl	2-Me 2 NC 6 H 4
786	1-piperazinylmethyl	4-pyridyl
787	1-piperazinylmethyl	3-pyridyl
788	1-piperazinylmethyl	2-pyridyl
789	1-piperazinylmethyl	2-thiazolyl
790	1-piperazinylmethyl	2-pyrazolyl
791	1-piperazinylmethyl	5-isoquinolyl
792	1-piperazinylmethyl	3,4-methylenedioxyC 6 H 3
793	1-piperazinylmethyl	3,4-ethylenedioxyC 6 H 3
794	1-piperazinylmethyl	2-imidazolyl
795	1-piperazinylmethyl	2-oxazolyl
796	1-piperazinylmethyl	4-isoxazolyl
797	1-piperazinylmethyl	4-HOC 6 H 4
798	1-piperazinylmethyl	3-HOC 6 H 4
799	1-piperazinylmethyl	3,4-diHOC 6 H 4
800	1-piperazinylmethyl	4-NH 2 CH 2 C 6 H 4
801	1-piperazinylmethyl	3-NH 2 CH 2 C 6 H 4

TABLE 3
Example
Number	R 1	R 2
802	2-pyridylmethyl	4-MeOC 6 H 4
803	2-pyridylmethyl	3-MeOC 6 H 4
804	2-pyridylmethyl	4-NH 2 C 6 H 4
805	2-pyridylmethyl	3-NH 2 C 6 H 4
806	2-pyridylmethyl	2-NH 2 C 6 H 4
807	2-pyridylmethyl	4-Me 2 NC 6 H 4
808	2-pyridylmethyl	3-Me 2 NC 6 H 4
809	2-pyridylmethyl	2-Me 2 NC 6 H 4
810	2-pyridylmethyl	4-pyridyl
811	2-pyridylmethyl	3-pyridyl
812	2-pyridylmethyl	2-pyridyl
813	2-pyridylmethyl	2-thiazolyl
814	2-pyridylmethyl	2-pyrazolyl
815	2-pyridylmethyl	5-isoquinolyl
816	2-pyridylmethyl	3,4-methylenedioxyC 6 H 3
817	2-pyridylmethyl	3,4-ethylenedioxyC 6 H 3
818	2-pyridylmethyl	2-imidazolyl
819	2-pyridylmethyl	2-oxazolyl
820	2-pyridylmethyl	4-isoxazolyl
821	2-pyridylmethyl	4-HOC 6 H 4
822	2-pyridylmethyl	3-HOC 6 H 4
823	2-pyridylmethyl	3,4-diHOC 6 H 4
824	2-pyridylmethyl	4-NH 2 CH 2 C 6 H 4
825	2-pyridylmethyl	3-NH 2 CH 2 C 6 H 4
826	3-pyridylmethyl	4-MeOC 6 H 4
827	3-pyridylmethyl	3-MeOC 6 H 4
828	3-pyridylmethyl	4-NH 2 C 6 H 4
829	3-pyridylmethyl	3-NH 2 C 6 H 4
830	3-pyridylmethyl	2-NH 2 C 6 H 4
831	3-pyridylmethyl	4-Me 2 NC 6 H 4
832	3-pyridylmethyl	3-Me 2 NC 6 H 4
833	3-pyridylmethyl	2-Me 2 NC 6 H 4
834	3-pyridylmethyl	4-pyridyl
835	3-pyridylmethyl	3-pyridyl
836	3-pyridylmethyl	2-pyridyl
837	3-pyridylmethyl	2-thiazolyl
838	3-pyridylmethyl	2-pyrazolyl
839	3-pyridylmethyl	5-isoquinolyl
840	3-pyridylmethyl	3,4-methylenedioxyC 6 H 3
841	3-pyridylmethyl	3,4-ethylenedioxyC 6 H 3
842	3-pyridylmethyl	2-imidazolyl
843	3-pyridylmethyl	2-oxazolyl
844	3-pyridylmethyl	4-isoxazolyl
845	3-pyridylmethyl	4-HOC 6 H 4
846	3-pyridylmethyl	3-HOC 6 H 4
847	3-pyridylmethyl	3,4-diHOC 6 H 4
848	3-pyridylmethyl	4-NH 2 CH 2 C 6 H 4
849	3-pyridylmethyl	3-NH 2 CH 2 C 6 H 4
850	4-pyridylmethyl	4-MeOC 6 H 4
851	4-pyridylmethyl	3-MeOC 6 H 4
852	4-pyridylmethyl	4-NH 2 C 6 H 4
853	4-pyridylmethyl	3-NH 2 C 6 H 4
854	4-pyridylmethyl	2-NH 2 C 6 H 4
855	4-pyridylmethyl	4-Me 2 NC 6 H 4
856	4-pyridylmethyl	3-Me 2 NC 6 H 4
857	4-pyridylmethyl	2-Me 2 NC 6 H 4
858	4-pyridylmethyl	4-pyridyl
859	4-pyridylmethyl	3-pyridyl
860	4-pyridylmethyl	2-pyridyl
861	4-pyridylmethyl	2-thiazolyl
862	4-pyridylmethyl	2-pyrazolyl
863	4-pyridylmethyl	5-isoquinolyl
864	4-pyridylmethyl	3,4-methylenedioxyC 6 H 3
865	4-pyridylmethyl	3,4-ethylenedioxyC 6 H 3
866	4-pyridylmethyl	2-imidazolyl
867	4-pyridylmethyl	2-oxazolyl
868	4-pyridylmethyl	4-isoxazolyl
869	4-pyridylmethyl	4-HOC 6 H 4
870	4-pyridylmethyl	3-HOC 6 H 4
871	4-pyridylmethyl	3,4-diHOC 6 H 4
872	4-pyridylmethyl	4-NH 2 CH 2 C 6 H 4
873	4-pyridylmethyl	3-NH 2 CH 2 C 6 H 4
874	2-NH 2 C 6 H 4	4-MeOC 6 H 4
875	2-NH 2 C 6 H 4	3-MeOC 6 H 4
876	2-NH 2 C 6 H 4	4-NH 2 C 6 H 4
877	2-NH 2 C 6 H 4	3-NH 2 C 6 H 4
878	2-NH 2 C 6 H 4	2-NH 2 C 6 H 4
879	2-NH 2 C 6 H 4	4-Me 2 NC 6 H 4
880	2-NH 2 C 6 H 4	3-Me 2 NC 6 H 4
881	2-NH 2 C 6 H 4	2-Me 2 NC 6 H 4
882	2-NH 2 C 6 H 4	4-pyridyl
883	2-NH 2 C 6 H 4	3-pyridyl
884	2-NH 2 C 6 H 4	2-pyridyl
885	2-NH 2 C 6 H 4	2-thiazolyl
886	2-NH 2 C 6 H 4	2-pyrazolyl
887	2-NH 2 C 6 H 4	5-isoquinolyl
888	2-NH 2 C 6 H 4	3,4-methylenedioxyC 6 H 3
889	2-NH 2 C 6 H 4	3,4-ethylenedioxyC 6 H 3
890	2-NH 2 C 6 H 4	2-imidazolyl
891	2-NH 2 C 6 H 4	2-oxazolyl
892	2-NH 2 C 6 H 4	4-isoxazolyl
893	2-NH 2 C 6 H 4	4-HOC 6 H 4
894	2-NH 2 C 6 H 4	3-HOC 6 H 4
895	2-NH 2 C 6 H 4	3,4-diHOC 6 H 4
896	2-NH 2 C 6 H 4	4-NH 2 CH 2 C 6 H 4
897	2-NH 2 C 6 H 4	3-NH 2 CH 2 C 6 H 4
898	3-NH 2 C 6 H 4	4-MeOC 6 H 4
899	3-NH 2 C 6 H 4	3-MeOC 6 H 4
900	3-NH 2 C 6 H 4	4-NH 2 C 6 H 4
901	3-NH 2 C 6 H 4	3-NH 2 C 6 H 4
902	3-NH 2 C 6 H 4	2-NH 2 C 6 H 4
903	3-NH 2 C 6 H 4	4-Me 2 NC 6 H 4
904	3-NH 2 C 6 H 4	3-Me 2 NC 6 H 4
905	3-NH 2 C 6 H 4	2-Me 2 NC 6 H 4
906	3-NH 2 C 6 H 4	4-pyridyl
907	3-NH 2 C 6 H 4	3-pyridyl
908	3-NH 2 C 6 H 4	2-pyridyl
909	3-NH 2 C 6 H 4	2-thiazolyl
910	3-NH 2 C 6 H 4	2-pyrazolyl
911	3-NH 2 C 6 H 4	5-isoquinolyl
912	3-NH 2 C 6 H 4	3,4-methylenedioxyC 6 H 3
913	3-NH 2 C 6 H 4	3,4-ethylenedioxyC 6 H 3
914	3-NH 2 C 6 H 4	2-imidazolyl
915	3-NH 2 C 6 H 4	2-oxazolyl
916	3-NH 2 C 6 H 4	4-isoxazolyl
917	3-NH 2 C 6 H 4	4-HOC 6 H 4
918	3-NH 2 C 6 H 4	3-HOC 6 H 4
919	3-NH 2 C 6 H 4	3,4-diHOC 6 H 4
920	3-NH 2 C 6 H 4	4-NH 2 CH 2 C 6 H 4
921	3-NH 2 C 6 H 4	3-NH 2 CH 2 C 6 H 4
922	4-NH 2 C 6 H 4	4-MeOC 6 H 4
923	4-NH 2 C 6 H 4	3-MeOC 6 H 4
924	4-NH 2 C 6 H 4	4-NH 2 C 6 H 4
925	4-NH 2 C 6 H 4	3-NH 2 C 6 H 4
926	4-NH 2 C 6 H 4	2-NH 2 C 6 H 4
927	4-NH 2 C 6 H 4	4-Me 2 NC 6 H 4
928	4-NH 2 C 6 H 4	3-Me 2 NC 6 H 4
930	4-NH 2 C 6 H 4	2-Me 2 NC 6 H 4
931	4-NH 2 C 6 H 4	4-pyridyl
932	4-NH 2 C 6 H 4	3-pyridyl
933	4-NH 2 C 6 H 4	2-pyridyl
934	4-NH 2 C 6 H 4	2-thiazolyl
935	4-NH 2 C 6 H 4	2-pyrazolyl
936	4-NH 2 C 6 H 4	5-isoquinolyl
937	4-NH 2 C 6 H 4	3,4-methylenedioxyC 6 H 3
938	4-NH 2 C 6 H 4	3,4-ethylenedioxyC 6 H 3
939	4-NH 2 C 6 H 4	2-imidazolyl
940	4-NH 2 C 6 H 4	2-oxazolyl
941	4-NH 2 C 6 H 4	4-isoxazolyl
942	4-NH 2 C 6 H 4	4-HOC 6 H 4
943	4-NH 2 C 6 H 4	3-HOC 6 H 4
944	4-NH 2 C 6 H 4	3,4-diHOC 6 H 4
945	4-NH 2 C 6 H 4	4-NH 2 CH 2 C 6 H 4
946	4-NH 2 C 6 H 4	3-NH 2 CH 2 C 6 H 4
947	2-MeOC 6 H 4	4-MeOC 6 H 4
948	2-MeOC 6 H 4	3-MeOC 6 H 4
949	2-MeOC 6 H 4	4-NH 2 C 6 H 4
950	2-MeOC 6 H 4	3-NH 2 C 6 H 4
951	2-MeOC 6 H 4	2-NH 2 C 6 H 4
952	2-MeOC 6 H 4	4-Me 2 NC 6 H 4
953	2-MeOC 6 H 4	3-Me 2 NC 6 H 4
954	2-MeOC 6 H 4	2-Me 2 NC 6 H 4
955	2-MeOC 6 H 4	4-pyridyl
956	2-MeOC 6 H 4	3-pyridyl
957	2-MeOC 6 H 4	2-pyridyl
958	2-MeOC 6 H 4	2-thiazolyl
959	2-MeOC 6 H 4	2-pyrazolyl
960	2-MeOC 6 H 4	5-isoquinolyl
961	2-MeOC 6 H 4	3,4-methylenedioxyC 6 H 3
962	2-MeOC 6 H 4	3-4-ethylenedioxyC 6 H 3
963	2-MeOC 6 H 4	2-imidazolyl
964	2-MeOC 6 H 4	2-oxazolyl
965	2-MeOC 6 H 4	4-isoxazolyl
966	2-MeOC 6 H 4	4-HOC 6 H 4
967	2-MeOC 6 H 4	3-HOC 6 H 4
968	2-MeOC 6 H 4	3,4-diHOC 6 H 4
969	2-MeOC 6 H 4	4-NH 2 CH 2 C 6 H 4
970	2-MeOC 6 H 4	3-NH 2 CH 2 C 6 H 4
971	3-MeOC 6 H 4	4-MeOC 6 H 4
972	3-MeOC 6 H 4	3-MeOC 6 H 4
973	3-MeOC 6 H 4	4-NH 2 C 6 H 4
974	3-MeOC 6 H 4	3-NH 2 C 6 H 4
975	3-MeOC 6 H 4	2-NH 2 C 6 H 4
976	3-MeOC 6 H 4	4-Me 2 NC 6 H 4
977	3-MeOC 6 H 4	3-Me 2 NC 6 H 4
978	3-MeOC 6 H 4	2-Me 2 NC 6 H 4
979	3-MeOC 6 H 4	4-pyridyl
980	3-MeOC 6 H 4	3-pyridyl
981	3-MeOC 6 H 4	2-pyridyl
982	3-MeOC 6 H 4	2-thiazolyl
983	3-MeOC 6 H 4	2-pyrazolyl
984	3-MeOC 6 H 4	5-isoquinolyl
985	3-MeOC 6 H 4	3,4-methylenedioxyC 6 H 3
986	3-MeOC 6 H 4	3,4-ethylenedioxyC 6 H 3
987	3-MeOC 6 H 4	2-imidazolyl
988	3-MeOC 6 H 4	2-oxazolyl
989	3-MeOC 6 H 4	4-isoxazolyl
990	3-MeOC 6 H 4	4-HOC 6 H 4
991	3-MeOC 6 H 4	3-HOC 6 H 4
992	3-MeOC 6 H 4	3,4-diHOC 6 H 4
993	3-MeOC 6 H 4	4-NH 2 CH 2 C 6 H 4
994	3-MeOC 6 H 4	3-NH 2 CH 2 C 6 H 4
995	4-MeOC 6 H 4	4-MeOC 6 H 4
996	4-MeOC 6 H 4	3-MeOC 6 H 4
997	4-MeOC 6 H 4	4-NH 2 C 6 H 4
998	4-MeOC 6 H 4	3-NH 2 C 6 H 4
999	4-MeOC 6 H 4	2-NH 2 C 6 H 4
1000	4-MeOC 6 H 4	4-Me 2 NC 6 H 4
1001	4-MeOC 6 H 4	3-Me 2 NC 6 H 4
1002	4-MeOC 6 H 4	2-Me 2 NC 6 H 4
1003	4-MeOC 6 H 4	4-pyridyl
1004	4-MeOC 6 H 4	3-pyridyl
1005	4-MeOC 6 H 4	2-pyridyl
1006	4-MeOC 6 H 4	2-thiazolyl
1007	4-MeOC 6 H 4	2-pyrazolyl
1008	4-MeOC 6 H 4	5-isoquinolyl
1009	4-MeOC 6 H 4	3,4-methylenedioxyC 6 H 3
1010	4-MeOC 6 H 4	3,4-ethylenedioxyC 6 H 3
1011	4-MeOC 6 H 4	2-imidazolyl
1012	4-MeOC 6 H 4	2-oxazolyl
1013	4-MeOC 6 H 4	4-isoxazolyl
1014	4-MeOC 6 H 4	4-HOC 6 H 4
1015	4-MeOC 6 H 4	3-HOC 6 H 4
1016	4-MeOC 6 H 4	3,4-diHOC 6 H 4
1017	4-MeOC 6 H 4	4-NH 2 CH 2 C 6 H 4
1018	4-MeOC 6 H 4	3-NH 2 CH 2 C 6 H 4
1019	2-HOC 6 H 4	4-MeOC 6 H 4
1020	2-HOC 6 H 4	3-MeOC 6 H 4
1021	2-HOC 6 H 4	4-NH 2 C 6 H 4
1022	2-HOC 6 H 4	3-NH 2 C 6 H 4
1023	2-HOC 6 H 4	2-NH 2 C 6 H 4
1024	2-HOC 6 H 4	4-Me 2 NC 6 H 4
1025	2-HOC 6 H 4	3-Me 2 NC 6 H 4
1026	2-HOC 6 H 4	2-Me 2 NC 6 H 4
1027	2-HOC 6 H 4	4-pyridyl
1028	2-HOC 6 H 4	3-pyridyl
1029	2-HOC 6 H 4	2-pyridyl
1030	2-HOC 6 H 4	2-thiazolyl
1031	2-HOC 6 H 4	2-pyrazolyl
1032	2-HOC 6 H 4	5-isoquinolyl
1033	2-HOC 6 H 4	3,4-methylenedioxyC 6 H 3
1034	2-HOC 6 H 4	3,4-ethylenedioxyC 6 H 3
1035	2-HOC 6 H 4	2-imidazolyl
1036	2-HOC 6 H 4	2-oxazolyl
1037	2-HOC 6 H 4	4-isoxazolyl
1038	2-HOC 6 H 4	4-HOC 6 H 4
1039	2-HOC 6 H 4	3-HOC 6 H 4
1040	2-HOC 6 H 4	3,4-diHOC 6 H 4
1041	2-HOC 6 H 4	4-NH 2 CH 2 C 6 H 4
1042	2-HOC 6 H 4	3-NH 2 CH 2 C 6 H 4
1043	3-HOC 6 H 4	4-MeOC 6 H 4
1044	3-HOC 6 H 4	3-MeOC 6 H 4
1045	3-HOC 6 H 4	4-NH 2 C 6 H 4
1046	3-HOC 6 H 4	3-NH 2 C 6 H 4
1047	3-HOC 6 H 4	2-NH 2 C 6 H 4
1048	3-HOC 6 H 4	4-Me 2 NC 6 H 4
1049	3-HOC 6 H 4	3-Me 2 NC 6 H 4
1050	3-HOC 6 H 4	2-Me 2 NC 6 H 4
1051	3-HOC 6 H 4	4-pyridyl
1052	3-HOC 6 H 4	3-pyridyl
1053	3-HOC 6 H 4	2-pyridyl
1054	3-HOC 6 H 4	2-thiazolyl
1055	3-HOC 6 H 4	2-pyrazolyl
1056	3-HOC 6 H 4	5-isoquinolyl
1057	3-HOC 6 H 4	3,4-methylenedioxyC 6 H 3
1058	3-HOC 6 H 4	3,4-ethylenedioxyC 6 H 3
1059	3-HOC 6 H 4	2-imidazolyl
1060	3-HOC 6 H 4	2-oxazolyl
1061	3-HOC 6 H 4	4-isoxazolyl
1062	3-HOC 6 H 4	4-HOC 6 H 4
1063	3-HOC 6 H 4	3-HOC 6 H 4
1064	3-HOC 6 H 4	3,4-diHOC 6 H 4
1065	3-HOC 6 H 4	4-NH 2 CH 2 C 6 H 4
1066	3-HOC 6 H 4	3-NH 2 CH 2 C 6 H 4
1067	4-HOC 6 H 4	4-MeOC 6 H 4
1068	4-HOC 6 H 4	3-MeOC 6 H 4
1069	4-HOC 6 H 4	4-NH 2 C 6 H 4
1070	4-HOC 6 H 4	3-NH 2 C 6 H 4
1071	4-HOC 6 H 4	2-NH 2 C 6 H 4
1072	4-HOC 6 H 4	4-Me 2 NC 6 H 4
1073	4-HOC 6 H 4	3-Me 2 NC 6 H 4
1074	4-HOC 6 H 4	2-Me 2 NC 6 H 4
1075	4-HOC 6 H 4	4-pyridyl
1076	4-HOC 6 H 4	3-pyridyl
1077	4-HOC 6 H 4	2-pyridyl
1078	4-HOC 6 H 4	2-thiazolyl
1079	4-HOC 6 H 4	2-pyrazolyl
1080	4-HOC 6 H 4	5-isoquinolyl
1081	4-HOC 6 H 4	3,4-methylenedioxyC 6 H 3
1082	4-HOC 6 H 4	3,4-ethylenedioxyC 6 H 3
1083	4-HOC 6 H 4	2-imidazolyl
1084	4-HOC 6 H 4	2-oxazolyl
1085	4-HOC 6 H 4	4-isoxazolyl
1086	4-HOC 6 H 4	4-HOC 6 H 4
1087	4-HOC 6 H 4	3-HOC 6 H 4
1088	4-HOC 6 H 4	3,4-diHOC 6 H 4
1089	4-HOC 6 H 4	4-NH 2 CH 2 C 6 H 4
1090	4-HOC 6 H 4	3-NH 2 CH 2 C 6 H 4
1091	4-ClC 6 H 4	4-MeOC 6 H 4
1092	4-ClC 6 H 4	3-MeOC 6 H 4
1093	4-ClC 6 H 4	4-NH 2 C 6 H 4
1094	4-ClC 6 H 4	3-NH 2 C 6 H 4
1095	4-ClC 6 H 4	2-NH 2 C 6 H 4
1096	4-ClC 6 H 4	4-Me 2 NC 6 H 4
1097	4-ClC 6 H 4	3-Me 2 NC 6 H 4
1098	4-ClC 6 H 4	2-Me 2 NC 6 H 4
1099	4-ClC 6 H 4	4-pyridyl
1100	4-ClC 6 H 4	3-pyridyl
1101	4-ClC 6 H 4	2-pyridyl
1102	4-ClC 6 H 4	2-thiazolyl
1103	4-ClC 6 H 4	2-pyrazolyl
1104	4-ClC 6 H 4	5-isoquinolyl
1105	4-ClC 6 H 4	3,4-methylenedioxyC 6 H 3
1106	4-ClC 6 H 4	3,4-ethylenedioxyC 6 H 3
1107	4-ClC 6 H 4	2-imidazolyl
1108	4-ClC 6 H 4	2-oxazolyl
1109	4-ClC 6 H 4	4-isoxazolyl
1110	4-ClC 6 H 4	4-HOC 6 H 4
1111	4-ClC 6 H 4	3-HOC 6 H 4
1112	4-ClC 6 H 4	3,4-diHOC 6 H 4
1113	4-ClC 6 H 4	4-NH 2 CH 2 C 6 H 4
1114	4-ClC 6 H 4	3-NH 2 CH 2 C 6 H 4
1115	2-NH 2 CH 2 C 6 H 4	4-MeOC 6 H 4
1116	2-NH 2 CH 2 C 6 H 4	3-MeOC 6 H 4
1117	2-NH 2 CH 2 C 6 H 4	4-NH 2 C 6 H 4
1118	2-NH 2 CH 2 C 6 H 4	3-NH 2 C 6 H 4
1119	2-NH 2 CH 2 C 6 H 4	2-NH 2 C 6 H 4
1120	2-NH 2 CH 2 C 6 H 4	4-Me 2 NC 6 H 4
1121	2-NH 2 CH 2 C 6 H 4	3-Me 2 NC 6 H 4
1122	2-NH 2 CH 2 C 6 H 4	2-Me 2 NC 6 H 4
1123	2-NH 2 CH 2 C 6 H 4	4-pyridyl
1124	2-NH 2 CH 2 C 6 H 4	3-pyridyl
1125	2-NH 2 CH 2 C 6 H 4	2-pyridyl
1126	2-NH 2 CH 2 C 6 H 4	2-thiazolyl
1127	2-NH 2 CH 2 C 6 H 4	2-pyrazolyl
1128	2-NH 2 CH 2 C 6 H 4	5-isoquinolyl
1129	2-NH 2 CH 2 C 6 H 4	3,4-methylenedioxyC 6 H 3
1130	2-NH 2 CH 2 C 6 H 4	3,4-ethylenedioxyC 6 H 3
1131	2-NH 2 CH 2 C 6 H 4	2-imidazolyl
1132	2-NH 2 CH 2 C 6 H 4	2-oxazolyl
1133	2-NH 2 CH 2 C 6 H 4	4-isoxazolyl
1134	2-NH 2 CH 2 C 6 H 4	4-HOC 6 H 4
1135	2-NH 2 CH 2 C 6 H 4	3-HOC 6 H 4
1136	2-NH 2 CH 2 C 6 H 4	3,4-diHOC 6 H 4
1137	2-NH 2 CH 2 C 6 H 4	4-NH 2 CH 2 C 6 H 4
1138	2-NH 2 CH 2 C 6 H 4	3-NH 2 CH 2 C 6 H 4
1139	3-NH 2 CH 2 C 6 H 4	4-MeOC 6 H 4
1140	3-NH 2 CH 2 C 6 H 4	3-MeOC 6 H 4
1141	3-NH 2 CH 2 C 6 H 4	4-NH 2 C 6 H 4
1142	3-NH 2 CH 2 C 6 H 4	3-NH 2 C 6 H 4
1143	3-NH 2 CH 2 C 6 H 4	2-NH 2 C 6 H 4
1144	3-NH 2 CH 2 C 6 H 4	4-Me 2 NC 6 H 4
1145	3-NH 2 CH 2 C 6 H 4	3-Me 2 NC 6 H 4
1146	3-NH 2 CH 2 C 6 H 4	2-Me 2 NC 6 H 4
1147	3-NH 2 CH 2 C 6 H 4	4-pyridyl
1148	3-NH 2 CH 2 C 6 H 4	3-pyridyl
1149	3-NH 2 CH 2 C 6 H 4	2-pyridyl
1150	3-NH 2 CH 2 C 6 H 4	2-thiazolyl
1151	3-NH 2 CH 2 C 6 H 4	2-pyrazolyl
1152	3-NH 2 CH 2 C 6 H 4	5-isoquinolyl
1153	3-NH 2 CH 2 C 6 H 4	3,4-methylenedioxyC 6 H 3
1154	3-NH 2 CH 2 C 6 H 4	3,4-ethylenedioxyC 6 H 3
1155	3-NH 2 CH 2 C 6 H 4	2-imidazolyl
1156	3-NH 2 CH 2 C 6 H 4	2-oxazolyl
1157	3-NH 2 CH 2 C 6 H 4	4-isoxazolyl
1158	3-NH 2 CH 2 C 6 H 4	4-HOC 6 H 4
1159	3-NH 2 CH 2 C 6 H 4	3-HOC 6 H 4
1160	3-NH 2 CH 2 C 6 H 4	3,4-diHOC 6 H 4
1161	3-NH 2 CH 2 C 6 H 4	4-NH 2 CH 2 C 6 H 4
1162	3-NH 2 CH 2 C 6 H 4	3-NH 2 CH 2 C 6 H 4
1163	4-NH 2 CH 2 C 6 H 4	4-MeOC 6 H 4
1164	4-NH 2 CH 2 C 6 H 4	3-MeOC 6 H 4
1165	4-NH 2 CH 2 C 6 H 4	4-NH 2 C 6 H 4
1166	4-NH 2 CH 2 C 6 H 4	3-NH 2 C 6 H 4
1167	4-NH 2 CH 2 C 6 H 4	2-NH 2 C 6 H 4
1168	4-NH 2 CH 2 C 6 H 4	4-Me 2 NC 6 H 4
1169	4-NH 2 CH 2 C 6 H 4	3-Me 2 NC 6 H 4
1170	4-NH 2 CH 2 C 6 H 4	2-Me 2 NC 6 H 4
1171	4-NH 2 CH 2 C 6 H 4	4-pyridyl
1172	4-NH 2 CH 2 C 6 H 4	3-pyridyl
1173	4-NH 2 CH 2 C 6 H 4	2-pyridyl
1174	4-NH 2 CH 2 C 6 H 4	2-thiazolyl
1175	4-NH 2 CH 2 C 6 H 4	2-pyrazolyl
1176	4-NH 2 CH 2 C 6 H 4	5-isoquinolyl
1177	4-NH 2 CH 2 C 6 H 4	3,4-methylenedioxyC 6 H 3
1178	4-NH 2 CH 2 C 6 H 4	3,4-ethylenedioxyC 6 H 3
1179	4-NH 2 CH 2 C 6 H 4	2-imidazolyl
1180	4-NH 2 CH 2 C 6 H 4	2-oxazolyl
1181	4-NH 2 CH 2 C 6 H 4	4-isoxazolyl
1182	4-NH 2 CH 2 C 6 H 4	4-HOC 6 H 4
1183	4-NH 2 CH 2 C 6 H 4	3-HOC 6 H 4
1184	4-NH 2 CH 2 C 6 H 4	3,4-diHOC 6 H 4
1185	4-NH 2 CH 2 C 6 H 4	4-NH 2 CH 2 C 6 H 4
1186	4-NH 2 CH 2 C 6 H 4	3-NH 2 CH 2 C 6 H 4
1187	2-Me 2 NCH 2 C 6 H 4	4-MeOC 6 H 4
1188	2-Me 2 NCH 2 C 6 H 4	3-MeOC 6 H 4
1189	2-Me 2 NCH 2 C 6 H 4	4-NH 2 C 6 H 4
1190	2-Me 2 NCH 2 C 6 H 4	3-NH 2 C 6 H 4
1191	2-Me 2 NCH 2 C 6 H 4	2-NH 2 C 6 H 4
1192	2-Me 2 NCH 2 C 6 H 4	4-Me 2 NC 6 H 4
1193	2-Me 2 NCH 2 C 6 H 4	3-Me 2 NC 6 H 4
1194	2-Me 2 NCH 2 C 6 H 4	2-Me 2 NC 6 H 4
1195	2-Me 2 NCH 2 C 6 H 4	4-pyridyl
1196	2-Me 2 NCH 2 C 6 H 4	3-pyridyl
1197	2-Me 2 NCH 2 C 6 H 4	2-pyridyl
1198	2-Me 2 NCH 2 C 6 H 4	2-thiazolyl
1199	2-Me 2 NCH 2 C 6 H 4	2-pyrazolyl
1200	2-Me 2 NCH 2 C 6 H 4	5-isoquinolyl
1201	2-Me 2 NCH 2 C 6 H 4	3,4-methylenedioxyC 6 H 3
1202	2-Me 2 NCH 2 C 6 H 4	3,4-ethylenedioxyC 6 H 3
1203	2-Me 2 NCH 2 C 6 H 4	2-imidazolyl
1204	2-Me 2 NCH 2 C 6 H 4	2-oxazolyl
1205	2-Me 2 NCH 2 C 6 H 4	4-isoxazolyl
1206	2-Me 2 NCH 2 C 6 H 4	4-HOC 6 H 4
1207	2-Me 2 NCH 2 C 6 H 4	3-HOC 6 H 4
1208	2-Me 2 NCH 2 C 6 H 4	3,4-diHOC 6 H 4
1209	2-Me 2 NCH 2 C 6 H 4	4-NH 2 CH 2 C 6 H 4
1210	2-Me 2 NCH 2 C 6 H 4	3-NH 2 CH 2 C 6 H 4
1211	3-Me 2 NCH 2 C 6 H 4	4-MeOC 6 H 4
1212	3-Me 2 NCH 2 C 6 H 4	3-MeOC 6 H 4
1213	3-Me 2 NCH 2 C 6 H 4	4-NH 2 C 6 H 4
1214	3-Me 2 NCH 2 C 6 H 4	3-NH 2 C 6 H 4
1215	3-Me 2 NCH 2 C 6 H 4	2-NH 2 C 6 H 4
1216	3-Me 2 NCH 2 C 6 H 4	4-Me 2 NC 6 H 4
1217	3-Me 2 NCH 2 C 6 H 4	3-Me 2 NC 6 H 4
1218	3-Me 2 NCH 2 C 6 H 4	2-Me 2 NC 6 H 4
1219	3-Me 2 NCH 2 C 6 H 4	4-pyridyl
1220	3-Me 2 NCH 2 C 6 H 4	3-pyridyl
1221	3-Me 2 NCH 2 C 6 H 4	2-pyridyl
1222	3-Me 2 NCH 2 C 6 H 4	2-thiazolyl
1223	3-Me 2 NCH 2 C 6 H 4	2-pyrazolyl
1224	3-Me 2 NCH 2 C 6 H 4	5-isoquinolyl
1225	3-Me 2 NCH 2 C 6 H 4	3,4-methylenedioxyC 6 H 3
1226	3-Me 2 NCH 2 C 6 H 4	3,4-ethylenedioxyC 6 H 3
1227	3-Me 2 NCH 2 C 6 H 4	2-imidazolyl
1228	3-Me 2 NCH 2 C 6 H 4	2-oxazolyl
1229	3-Me 2 NCH 2 C 6 H 4	4-isoxazolyl
1230	3-Me 2 NCH 2 C 6 H 4	4-HOC 6 H 4
1231	3-Me 2 NCH 2 C 6 H 4	3-HOC 6 H 4
1232	3-Me 2 NCH 2 C 6 H 4	3,4-diHOC 6 H 4
1233	3-Me 2 NCH 2 C 6 H 4	4-NH 2 CH 2 C 6 H 4
1234	3-Me 2 NCH 2 C 6 H 4	3-NH 2 CH 2 C 6 H 4
1235	4-Me 2 NCH 2 C 6 H 4	4-MeOC 6 H 4
1236	4-Me 2 NCH 2 C 6 H 4	3-MeOC 6 H 4
1237	4-Me 2 NCH 2 C 6 H 4	4-NH 2 C 6 H 4
1238	4-Me 2 NCH 2 C 6 H 4	3-NH 2 C 6 H 4
1239	4-Me 2 NCH 2 C 6 H 4	2-NH 2 C 6 H 4
1240	4-Me 2 NCH 2 C 6 H 4	4-Me 2 NC 6 H 4
1241	4-Me 2 NCH 2 C 6 H 4	3-Me 2 NC 6 H 4
1242	4-Me 2 NCH 2 C 6 H 4	2-Me 2 NC 6 H 4
1243	4-Me 2 NCH 2 C 6 H 4	4-pyridyl
1244	4-Me 2 NCH 2 C 6 H 4	3-pyridyl
1245	4-Me 2 NCH 2 C 6 H 4	2-pyridyl
1246	4-Me 2 NCH 2 C 6 H 4	2-thiazolyl
1247	4-Me 2 NCH 2 C 6 H 4	2-pyrazolyl
1248	4-Me 2 NCH 2 C 6 H 4	5-isoquinolyl
1249	4-Me 2 NCH 2 C 6 H 4	3,4-methylenedioxyC 6 H 3
1250	4-Me 2 NCH 2 C 6 H 4	3,4-ethylenedioxyC 6 H 3
1251	4-Me 2 NCH 2 C 6 H 4	2-imidazolyl
1252	4-Me 2 NCH 2 C 6 H 4	2-oxazolyl
1253	4-Me 2 NCH 2 C 6 H 4	4-isoxazolyl
1254	4-Me 2 NCH 2 C 6 H 4	4-HOC 6 H 4
1255	4-Me 2 NCH 2 C 6 H 4	3-HOC 6 H 4
1256	4-Me 2 NCH 2 C 6 H 4	3,4-diHOC 6 H 4
1257	4-Me 2 NCH 2 C 6 H 4	4-NH 2 CH 2 C 6 H 4
1258	4-Me 2 NCH 2 C 6 H 4	3-NH 2 CH 2 C 6 H 4
1259	H	4-MeOC 6 H 4
1260	H	3-MeOC 6 H 4
1261	H	4-NH 2 C 6 H 4
1262	H	3-NH 2 C 6 H 4
1263	H	2-NH 2 C 6 H 4
1264	H	4-Me 2 NC 6 H 4
1265	H	3-Me 2 NC 6 H 4
1266	H	2-Me 2 NC 6 H 4
1267	H	4-pyridyl
1268	H	3-pyridyl
1269	H	2-pyridyl
1270	H	2-thiazolyl
1271	H	2-pyrazolyl
1272	H	5-isoquinolyl
1273	H	3,4-methylenedioxyC 6 H 3
1274	H	3,4-ethylenedioxyC 6 H 3
1275	H	2-imidazolyl
1276	H	2-oxazolyl
1277	H	4-isoxazolyl
1278	H	4-HOC 6 H 4
1279	H	3-HOC 6 H 4
1280	H	3,4-diHOC 6 H 4
1281	H	4-NH 2 CH 2 C 6 H 4
1282	H	3-NH 2 CH 2 C 6 H 4
1283	Me	4-MeOC 6 H 4
1284	Me	3-MeOC 6 H 4
1285	Me	4-NH 2 C 6 H 4
1286	Me	3-NH 2 C 6 H 4
1287	Me	2-NH 2 C 6 H 4
1288	Me	4-Me 2 NC 6 H 4
1289	Me	3-Me 2 NC 6 H 4
1290	Me	2-Me 2 NC 6 H 4
1291	Me	4-pyridyl
1292	Me	3-pyridyl
1293	Me	2-pyridyl
1294	Me	2-thiazolyl
1295	Me	2-pyrazolyl
1296	Me	5-isoquinolyl
1297	Me	3,4-methylenedioxyC 6 H 3
1298	Me	3,4-ethylenedioxyC 6 H 3
1299	Me	2-imidazolyl
1300	Me	2-oxazolyl
1301	Me	4-isoxazolyl
1302	Me	4-HOC 6 H 4
1303	Me	3-HOC 6 H 4
1304	Me	3,4-diHOC 6 H 4
1305	Me	4-NH 2 CH 2 C 6 H 4
1306	Me	3-NH 2 CH 2 C 6 H 4
1307	Et	4-MeOC 6 H 4
1308	Et	3-MeOC 6 H 4
1309	Et	4-NH 2 C 6 H 4
1310	Et	3-NH 2 C 6 H 4
1311	Et	2-NH 2 C 6 H 4
1312	Et	4-Me 2 NC 6 H 4
1313	Et	3-Me 2 NC 6 H 4
1314	Et	2-Me 2 NC 6 H 4
1315	Et	4-pyridyl
1316	Et	3-pyridyl
1317	Et	2-pyridyl
1318	Et	2-thiazolyl
1319	Et	2-pyrazolyl
1320	Et	5-isoquinolyl
1321	Et	3,4-methylenedioxyC 6 H 3
1322	Et	3,4-ethylenedioxyC 6 H 3
1323	Et	2-imidazolyl
1324	Et	2-oxazolyl
1325	Et	4-isoxazolyl
1326	Et	4-HOC 6 H 4
1327	Et	3-HOC 6 H 4
1328	Et	3,4-diHOC 6 H 4
1329	Et	4-NH 2 CH 2 C 6 H 4
1330	Et	3-NH 2 CH 2 C 6 H 4
1331	2-NH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
1332	2-NH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
1333	2-NH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
1334	2-NH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
1335	2-NH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
1336	2-NH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
1337	2-NH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
1338	2-NH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
1339	2-NH 2 C 6 H 4 CH 2	4-pyridyl
1340	2-NH 2 C 6 H 4 CH 2	3-pyridyl
1341	2-NH 2 C 6 H 4 CH 2	2-pyridyl
1342	2-NH 2 C 6 H 4 CH 2	2-thiazolyl
1343	2-NH 2 C 6 H 4 CH 2	2-pyrazolyl
1344	2-NH 2 C 6 H 4 CH 2	5-isoquinolyl
1345	2-NH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1346	2-NH 2 C 6 H 4 CH 2	3-4-ethylenedioxyC 6 H 3
1347	2-NH 2 C 6 H 4 CH 2	2-imidazolyl
1348	2-NH 2 C 6 H 4 CH 2	2-oxazolyl
1349	2-NH 2 C 6 H 4 CH 2	4-isoxazolyl
1350	2-NH 2 C 6 H 4 CH 2	4-HOC 6 H 4
1351	2-NH 2 C 6 H 4 CH 2	3-HOC 6 H 4
1352	2-NH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
1353	2-NH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1354	2-NH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
1355	3-NH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
1356	3-NH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
1357	3-NH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
1358	3-NH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
1359	3-NH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
1360	3-NH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
1361	3-NH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
1362	3-NH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
1363	3-NH 2 C 6 H 4 CH 2	4-pyridyl
1364	3-NH 2 C 6 H 4 CH 2	3-pyridyl
1365	3-NH 2 C 6 H 4 CH 2	2-pyridyl
1366	3-NH 2 C 6 H 4 CH 2	2-thiazolyl
1367	3-NH 2 C 6 H 4 CH 2	2-pyrazolyl
1367	3-NH 2 C 6 H 4 CH 2	5-isoquinolyl
1369	3-NH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1370	3-NH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
1371	3-NH 2 C 6 H 4 CH 2	2-imidazolyl
1372	3-NH 2 C 6 H 4 CH 2	2-oxazolyl
1373	3-NH 2 C 6 H 4 CH 2	4-isoxazolyl
1374	3-NH 2 C 6 H 4 CH 2	4-HOC 6 H 4
1375	3-NH 2 C 6 H 4 CH 2	3-HOC 6 H 4
1376	3-NH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
1377	3-NH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1378	3-NH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
1379	4-NH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
1380	4-NH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
1381	4-NH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
1382	4-NH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
1383	4-NH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
1384	4-NH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
1385	4-NH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
1386	4-NH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
1387	4-NH 2 C 6 H 4 CH 2	4-pyridyl
1388	4-NH 2 C 6 H 4 CH 2	3-pyridyl
1389	4-NH 2 C 6 H 4 CH 2	2-pyridyl
1390	4-NH 2 C 6 H 4 CH 2	2-thiazolyl
1391	4-NH 2 C 6 H 4 CH 2	2-pyrazolyl
1392	4-NH 2 C 6 H 4 CH 2	5-isoquinolyl
1393	4-NH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1394	4-NH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
1395	4-NH 2 C 6 H 4 CH 2	2-imidazolyl
1396	4-NH 2 C 6 H 4 CH 2	2-oxazolyl
1397	4-NH 2 C 6 H 4 CH 2	4-isoxazolyl
1398	4-NH 2 C 6 H 4 CH 2	4-HOC 6 H 4
1399	4-NH 2 C 6 H 4 CH 2	3-HOC 6 H 4
1400	4-NH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
1401	4-NH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1402	4-NH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
1403	2-MeOC 6 H 4 CH 2	4-MeOC 6 H 4
1404	2-MeOC 6 H 4 CH 2	3-MeOC 6 H 4
1405	2-MeOC 6 H 4 CH 2	4-NH 2 C 6 H 4
1406	2-MeOC 6 H 4 CH 2	3-NH 2 C 6 H 4
1407	2-MeOC 6 H 4 CH 2	2-NH 2 C 6 H 4
1408	2-MeOC 6 H 4 CH 2	4-Me 2 NC 6 H 4
1409	2-MeOC 6 H 4 CH 2	3-Me 2 NC 6 H 4
1410	2-MeOC 6 H 4 CH 2	2-Me 2 NC 6 H 4
1411	2-MeOC 6 H 4 CH 2	4-pyridyl
1412	2-MeOC 6 H 4 CH 2	3-pyridyl
1413	2-MeOC 6 H 4 CH 2	2-pyridyl
1414	2-MeOC 6 H 4 CH 2	2-thiazolyl
1415	2-MeOC 6 H 4 CH 2	2-pyrazolyl
1416	2-MeOC 6 H 4 CH 2	5-isoquinolyl
1417	2-MeOC 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1418	2-MeOC 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
1419	2-MeOC 6 H 4 CH 2	2-imidazolyl
1420	2-MeOC 6 H 4 CH 2	2-oxazolyl
1421	2-MeOC 6 H 4 CH 2	4-isoxazolyl
1422	2-MeOC 6 H 4 CH 2	4-HOC 6 H 4
1423	2-MeOC 6 H 4 CH 2	3-HOC 6 H 4
1424	2-MeOC 6 H 4 CH 2	3,4-diHOC 6 H 4
1425	2-MeOC 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1426	2-MeOC 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
1427	3-MeOC 6 H 4 CH 2	4-MeOC 6 H 4
1428	3-MeOC 6 H 4 CH 2	3-MeOC 6 H 4
1429	3-MeOC 6 H 4 CH 2	4-NH 2 C 6 H 4
1430	3-MeOC 6 H 4 CH 2	3-NH 2 C 6 H 4
1431	3-MeOC 6 H 4 CH 2	2-NH 2 C 6 H 4
1432	3-MeOC 6 H 4 CH 2	4-Me 2 NC 6 H 4
1433	3-MeOC 6 H 4 CH 2	3-Me 2 NC 6 H 4
1434	3-MeOC 6 H 4 CH 2	2-Me 2 NC 6 H 4
1435	3-MeOC 6 H 4 CH 2	4-pyridyl
1436	3-MeOC 6 H 4 CH 2	3-pyridyl
1437	3-MeOC 6 H 4 CH 2	2-pyridyl
1438	3-MeOC 6 H 4 CH 2	2-thiazolyl
1439	3-MeOC 6 H 4 CH 2	2-pyrazolyl
1440	3-MeOC 6 H 4 CH 2	5-isoquinolyl
1441	3-MeOC 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1442	3-MeOC 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
1443	3-MeOC 6 H 4 CH 2	2-imidazolyl
1444	3-MeOC 6 H 4 CH 2	2-oxazolyl
1445	3-MeOC 6 H 4 CH 2	4-isoxazolyl
1446	3-MeOC 6 H 4 CH 2	4-HOC 6 H 4
1447	3-MeOC 6 H 4 CH 2	3-HOC 6 H 4
1448	3-MeOC 6 H 4 CH 2	3,4-diHOC 6 H 4
1449	3-MeOC 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1450	3-MeOC 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
1451	4-MeOC 6 H 4 CH 2	4-MeOC 6 H 4
1452	4-MeOC 6 H 4 CH 2	3-MeOC 6 H 4
1453	4-MeOC 6 H 4 CH 2	4-NH 2 C 6 H 4
1454	4-MeOC 6 H 4 CH 2	3-NH 2 C 6 H 4
1455	4-MeOC 6 H 4 CH 2	2-NH 2 C 6 H 4
1456	4-MeOC 6 H 4 CH 2	4-Me 2 NC 6 H 4
1457	4-MeOC 6 H 4 CH 2	3-Me 2 NC 6 H 4
1458	4-MeOC 6 H 4 CH 2	2-Me 2 NC 6 H 4
1459	4-MeOC 6 H 4 CH 2	4-pyridyl
1460	4-MeOC 6 H 4 CH 2	3-pyridyl
1461	4-MeOC 6 H 4 CH 2	2-pyridyl
1462	4-MeOC 6 H 4 CH 2	2-thiazolyl
1463	4-MeOC 6 H 4 CH 2	2-pyrazolyl
1464	4-MeOC 6 H 4 CH 2	5-isoquinolyl
1465	4-MeOC 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1466	4-MeOC 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
1467	4-MeOC 6 H 4 CH 2	2-imidazolyl
1468	4-MeOC 6 H 4 CH 2	2-oxazolyl
1469	4-MeOC 6 H 4 CH 2	4-isoxazolyl
1470	4-MeOC 6 H 4 CH 2	4-HOC 6 H 4
1471	4-MeOC 6 H 4 CH 2	3-HOC 6 H 4
1472	4-MeOC 6 H 4 CH 2	3,4-diHOC 6 H 4
1473	4-MeOC 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1474	4-MeOC 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
1475	2-HOC 6 H 4 CH 2	4-MeOC 6 H 4
1476	2-HOC 6 H 4 CH 2	3-MeOC 6 H 4
1477	2-HOC 6 H 4 CH 2	4-NH 2 C 6 H 4
1478	2-HOC 6 H 4 CH 2	3-NH 2 C 6 H 4
1479	2-HOC 6 H 4 CH 2	2-NH 2 C 6 H 4
1480	2-HOC 6 H 4 CH 2	4-Me 2 NC 6 H 4
1481	2-HOC 6 H 4 CH 2	3-Me 2 NC 6 H 4
1482	2-HOC 6 H 4 CH 2	2-Me 2 NC 6 H 4
1483	2-HOC 6 H 4 CH 2	4-pyridyl
1484	2-HOC 6 H 4 CH 2	3-pyridyl
1485	2-HOC 6 H 4 CH 2	2-pyridyl
1486	2-HOC 6 H 4 CH 2	2-thiazolyl
1487	2-HOC 6 H 4 CH 2	2-pyrazolyl
1488	2-HOC 6 H 4 CH 2	5-isoquinolyl
1489	2-HOC 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1490	2-HOC 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
1491	2-HOC 6 H 4 CH 2	2-imidazolyl
1492	2-HOC 6 H 4 CH 2	2-oxazolyl
1493	2-HOC 6 H 4 CH 2	4-isoxazolyl
1494	2-HOC 6 H 4 CH 2	4-HOC 6 H 4
1495	2-HOC 6 H 4 CH 2	3-HOC 6 H 4
1496	2-HOC 6 H 4 CH 2	3,4-diHOC 6 H 4
1497	2-HOC 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1498	2-HOC 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
1499	3-HOC 6 H 4 CH 2	4-MeOC 6 H 4
1500	3-HOC 6 H 4 CH 2	3-MeOC 6 H 4
1501	3-HOC 6 H 4 CH 2	4-NH 2 C 6 H 4
1502	3-HOC 6 H 4 CH 2	3-NH 2 C 6 H 4
1503	3-HOC 6 H 4 CH 2	2-NH 2 C 6 H 4
1504	3-HOC 6 H 4 CH 2	4-Me 2 NC 6 H 4
1505	3-HOC 6 H 4 CH 2	3-Me 2 NC 6 H 4
1506	3-HOC 6 H 4 CH 2	2-Me 2 NC 6 H 4
1507	3-HOC 6 H 4 CH 2	4-pyridyl
1508	3-HOC 6 H 4 CH 2	3-pyridyl
1509	3-HOC 6 H 4 CH 2	2-pyridyl
1510	3-HOC 6 H 4 CH 2	2-thiazolyl
1511	3-HOC 6 H 4 CH 2	2-pyrazolyl
1512	3-HOC 6 H 4 CH 2	5-isoquinolyl
1513	3-HOC 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1514	3-HOC 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
1514	3-HOC 6 H 4 CH 2	2-imidazolyl
1516	3-HOC 6 H 4 CH 2	2-oxazolyl
1517	3-HOC 6 H 4 CH 2	4-isoxazolyl
1518	3-HOC 6 H 4 CH 2	4-HOC 6 H 4
1519	3-HOC 6 H 4 CH 2	3-HOC 6 H 4
1520	3-HOC 6 H 4 CH 2	3,4-diHOC 6 H 4
1521	3-HOC 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1522	3-HOC 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
1523	4-HOC 6 H 4 CH 2	4-MeOC 6 H 4
1524	4-HOC 6 H 4 CH 2	3-MeOC 6 H 4
1525	4-HOC 6 H 4 CH 2	4-NH 2 C 6 H 4
1526	4-HOC 6 H 4 CH 2	3-NH 2 C 6 H 4
1527	4-HOC 6 H 4 CH 2	2-NH 2 C 6 H 4
1528	4-HOC 6 H 4 CH 2	4-Me 2 NC 6 H 4
1529	4-HOC 6 H 4 CH 2	3-Me 2 NC 6 H 4
1530	4-HOC 6 H 4 CH 2	2-Me 2 NC 6 H 4
1531	4-HOC 6 H 4 CH 2	4-pyridyl
1532	4-HOC 6 H 4 CH 2	3-pyridyl
1533	4-HOC 6 H 4 CH 2	2-pyridyl
1534	4-HOC 6 H 4 CH 2	2-thiazolyl
1535	4-HOC 6 H 4 CH 2	2-pyrazolyl
1536	4-HOC 6 H 4 CH 2	5-isoquinolyl
1537	4-HOC 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1538	4-HOC 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
1539	4-HOC 6 H 4 CH 2	2-imidazolyl
1540	4-HOC 6 H 4 CH 2	2-oxazolyl
1541	4-HOC 6 H 4 CH 2	4-isoxazolyl
1542	4-HOC 6 H 4 CH 2	4-HOC 6 H 4
1543	4-HOC 6 H 4 CH 2	3-HOC 6 H 4
1544	4-HOC 6 H 4 CH 2	3,4-diHOC 6 H 4
1545	4-HOC 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1546	4-HOC 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
1547	4-ClC 6 H 4 CH 2	4-MeOC 6 H 4
1548	4-ClC 6 H 4 CH 2	3-MeOC 6 H 4
1549	4-ClC 6 H 4 CH 2	4-NH 2 C 6 H 4
1550	4-ClC 6 H 4 CH 2	3-NH 2 C 6 H 4
1551	4-ClC 6 H 4 CH 2	2-NH 2 C 6 H 4
1552	4-ClC 6 H 4 CH 2	4-Me 2 NC 6 H 4
1553	4-ClC 6 H 4 CH 2	3-Me 2 NC 6 H 4
1554	4-ClC 6 H 4 CH 2	2-Me 2 NC 6 H 4
1555	4-ClC 6 H 4 CH 2	4-pyridyl
1556	4-ClC 6 H 4 CH 2	3-pyridyl
1557	4-ClC 6 H 4 CH 2	2-pyridyl
1558	4-ClC 6 H 4 CH 2	2-thiazolyl
1559	4-ClC 6 H 4 CH 2	2-pyrazolyl
1560	4-ClC 6 H 4 CH 2	5-isoquinolyl
1561	4-ClC 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1562	4-ClC 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
1563	4-ClC 6 H 4 CH 2	2-imidazolyl
1564	4-ClC 6 H 4 CH 2	2-oxazolyl
1565	4-ClC 6 H 4 CH 2	4-isoxazolyl
1566	4-ClC 6 H 4 CH 2	4-HOC 6 H 4
1567	4-ClC 6 H 4 CH 2	3-HOC 6 H 4
1568	4-ClC 6 H 4 CH 2	3,4-diHOC 6 H 4
1569	4-ClC 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1570	4-ClC 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
1571	2-NH 2 CH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
1572	2-NH 2 CH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
1573	2-NH 2 CH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
1574	2-NH 2 CH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
1575	2-NH 2 CH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
1576	2-NH 2 CH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
1577	2-NH 2 CH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
1578	2-NH 2 CH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
1579	2-NH 2 CH 2 C 6 H 4 CH 2	4-pyridyl
1580	2-NH 2 CH 2 C 6 H 4 CH 2	3-pyridyl
1581	2-NH 2 CH 2 C 6 H 4 CH 2	2-pyridyl
1582	2-NH 2 CH 2 C 6 H 4 CH 2	2-thiazolyl
1583	2-NH 2 CH 2 C 6 H 4 CH 2	2-pyrazolyl
1584	2-NH 2 CH 2 C 6 H 4 CH 2	5-isoquinolyl
1585	2-NH 2 CH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1586	2-NH 2 CH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
1587	2-NH 2 CH 2 C 6 H 4 CH 2	2-imidazolyl
1588	N-NH 2 CH 2 C 6 H 4 CH 2	2-oxazolyl
1589	2-NH 2 CH 2 C 6 H 4 CH 2	4-isoxazolyl
1590	2-NH 2 CH 2 C 6 H 4 CH 2	4-HOC 6 H 4
1591	2-NH 2 CH 2 C 6 H 4 CH 2	3-HOC 6 H 4
1592	2-NH 2 CH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
1593	2-NH 2 CH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1594	2-NH 2 CH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
1595	3-NH 2 CH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
1596	3-NH 2 CH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
1597	3-NH 2 CH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
1598	3-NH 2 CH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
1599	3-NH 2 CH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
1600	3-NH 2 CH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
1601	3-NH 2 CH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
1602	3-NH 2 CH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
1603	3-NH 2 CH 2 C 6 H 4 CH 2	4-pyridyl
1604	3-NH 2 CH 2 C 6 H 4 CH 2	3-pyridyl
1605	3-NH 2 CH 2 C 6 H 4 CH 2	2-pyridyl
1606	3-NH 2 CH 2 C 6 H 4 CH 2	2-thiazolyl
1607	3-NH 2 CH 2 C 6 H 4 CH 2	2-pyrazolyl
1608	3-NH 2 CH 2 C 6 H 4 CH 2	5-isoquinolyl
1609	3-NH 2 CH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1610	3-NH 2 CH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
1611	3-NH 2 CH 2 C 6 H 4CH 2	2-imidazolyl
1612	3-NH 2 CH 2 C 6 H 4 CH 2	2-oxazolyl
1613	3-NH 2 CH 2 C 6 H 4 CH 2	4-isoxazolyl
1614	3-NH 2 CH 2 C 6 H 4 CH 2	4-HOC 6 H 4
1615	3-NH 2 CH 2 C 6 H 4 CH 2	3-HOC 6 H 4
1616	3-NH 2 CH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
1617	3-NH 2 CH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1618	3-NH 2 CH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
1619	4-NH 2 CH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
1620	4-NH 2 CH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
1621	4-NH 2 CH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
1622	4-NH 2 CH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
1623	4-NH 2 CH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
1624	4-NH 2 CH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
1625	4-NH 2 CH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
1626	4-NH 2 CH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
1627	4-NH 2 CH 2 C 6 H 4 CH 2	4-pyridyl
1628	4-NH 2 CH 2 C 6 H 4 CH 2	3-pyridyl
1629	4-NH 2 CH 2 C 6 H 4 CH 2	2-pyridyl
1630	4-NH 2 CH 2 C 6 H 4 CH 2	2-thiazolyl
1631	4-NH 2 CH 2 C 6 H 4 CH 2	2-pyrazolyl
1632	4-NH 2 CH 2 C 6 H 4 CH 2	5-isoquinolyl
1633	4-NH 2 CH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1634	4-NH 2 CH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
1635	4-NH 2 CH 2 C 6 H 4 CH 2	2-imidazolyl
1636	4-NH 2 CH 2 C 6 H 4 CH 2	2-oxazolyl
1637	4-NH 2 CH 2 C 6 H 4 CH 2	4-isoxazolyl
1638	4-NH 2 CH 2 C 6 H 4 CH 2	4-HOC 6 H 4
1639	4-NH 2 CH 2 C 6 H 4 CH 2	3-HOC 6 H 4
1640	4-NH 2 CH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
1641	4-NH 2 CH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1642	4-NH 2 CH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
1643	2-Me 2 NCH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
1644	2-Me 2 NCH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
1645	2-Me 2 NCH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
1646	2-Me 2 NCH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
1647	2-Me 2 NCH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
1648	2-Me 2 NCH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
1649	2-Me 2 NCH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
1650	2-Me 2 NCH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
1651	2-Me 2 NCH 2 C 6 H 4 CH 2	4-pyridyl
1652	2-Me 2 NCH 2 C 6 H 4 CH 2	3-pyridyl
1653	2-Me 2 NCH 2 C 6 H 4 CH 2	2-pyridyl
1654	2-Me 2 NCH 2 C 6 H 4 CH 2	2-thiazolyl
1655	2-Me 2 NCH 2 C 6 H 4 CH 2	2-pyrazolyl
1656	2-Me 2 NCH 2 C 6 H 4 CH 2	5-isoquinolyl
1657	2-Me 2 NCH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1658	2-Me 2 NCH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
1659	2-Me 2 NCH 2 C 6 H 4 CH 2	2-imidazolyl
1660	2-Me 2 NCH 2 C 6 H 4 CH 2	2-oxazolyl
1661	2-Me 2 NCH 2 C 6 H 4 CH 2	4-isoxazolyl
1662	2-Me 2 NCH 2 C 6 H 4 CH 2	4-HOC 6 H 4
1663	2-Me 2 NCH 2 C 6 H 4 CH 2	3-HOC 6 H 4
1664	2-Me 2 NCH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
1665	2-Me 2 NCH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1666	2-Me 2 NCH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
1667	3-Me 2 NCH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
1668	3-Me 2 NCH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
1669	3-Me 2 NCH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
1670	3-Me 2 NCH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
1671	3-Me 2 NCH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
1672	3-Me 2 NCH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
1673	3-Me 2 NCH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
1674	3-Me 2 NCH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
1675	3-Me 2 NCH 2 C 6 H 4 CH 2	4-pyridyl
1676	3-Me 2 NCH 2 C 6 H 4 CH 2	3-pyridyl
1677	3-Me 2 NCH 2 C 6 H 4 CH 2	2-pyridyl
1678	3-Me 2 NCH 2 C 6 H 4 CH 2	2-thiazolyl
1679	3-Me 2 NCH 2 C 6 H 4 CH 2	2-pyrazolyl
1680	3-Me 2 NCH 2 C 6 H 4 CH 2	5-isoquinolyl
1681	3-Me 2 NCH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1682	3-Me 2 NCH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
1683	3-Me 2 NCH 2 C 6 H 4 CH 2	2-imidazolyl
1684	3-Me 2 NCH 2 C 6 H 4 CH 2	2-oxazolyl
1685	3-Me 2 NCH 2 C 6 H 4 CH 2	4-isoxazolyl
1686	3-Me 2 NCH 2 C 6 H 4 CH 2	4-HOC 6 H 4
1687	3-Me 2 NCH 2 C 6 H 4 CH 2	3-HOC 6 H 4
1688	3-Me 2 NCH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
1689	3-Me 2 NCH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1690	3-Me 2 NCH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4
1691	4-Me 2 NCH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
1692	4-Me 2 NCH 2 C 6 H 4 CH 2	3-MeOC 6 H 4
1693	4-Me 2 NCH 2 C 6 H 4 CH 2	4-NH 2 C 6 H 4
1694	4-Me 2 NCH 2 C 6 H 4 CH 2	3-NH 2 C 6 H 4
1695	4-Me 2 NCH 2 C 6 H 4 CH 2	2-NH 2 C 6 H 4
1696	4-Me 2 NCH 2 C 6 H 4 CH 2	4-Me 2 NC 6 H 4
1697	4-Me 2 NCH 2 C 6 H 4 CH 2	3-Me 2 NC 6 H 4
1698	4-Me 2 NCH 2 C 6 H 4 CH 2	2-Me 2 NC 6 H 4
1699	4-Me 2 NCH 2 C 6 H 4 CH 2	4-pyridyl
1700	4-Me 2 NCH 2 C 6 H 4 CH 2	3-pyridyl
1701	4-Me 2 NCH 2 C 6 H 4 CH 2	2-pyridyl
1702	4-Me 2 NCH 2 C 6 H 4 CH 2	2-thiazolyl
1703	4-Me 2 NCH 2 C 6 H 4 CH 2	2-pyrazolyl
1704	4-Me 2 NCH 2 C 6 H 4 CH 2	5-isoquinolyl
1705	4-Me 2 NCH 2 C 6 H 4 CH 2	3,4-methylenedioxyC 6 H 3
1706	4-Me 2 NCH 2 C 6 H 4 CH 2	3,4-ethylenedioxyC 6 H 3
1707	4-Me 2 NCH 2 C 6 H 4 CH 2	2-imidazolyl
1708	4-Me 2 NCH 2 C 6 H 4 CH 2	2-oxazolyl
1709	4-Me 2 NCH 2 C 6 H 4 CH 2	4-isoxazolyl
1710	4-Me 2 NCH 2 C 6 H 4 CH 2	4-HOC 6 H 4
1711	4-Me 2 NCH 2 C 6 H 4 CH 2	3-HOC 6 H 4
1712	4-Me 2 NCH 2 C 6 H 4 CH 2	3,4-diHOC 6 H 4
1713	4-Me 2 NCH 2 C 6 H 4 CH 2	4-NH 2 CH 2 C 6 H 4
1714	4-Me 2 NCH 2 C 6 H 4 CH 2	3-NH 2 CH 2 C 6 H 4

TABLE 4
Example
Number	R 1	R 2
1715	Methyl	4-MeOC 6 H 4
1716	ClCH 2	4-MeOC 6 H 4
1717	Cyclopropyl	4-MeOC 6 H 4
1718	Isopropyl	4-MeOC 6 H 4
1719	Ethyl	4-MeOC 6 H 4
1720	Cyclopentyl	4-MeOC 6 H 4
1721	Cyclobutyl	4-MeOC 6 H 4
1722	Benzyl	4-MeOC 6 H 4
1723	n-propyl	4-MeOC 6 H 4
1724	4-ClC 6 H 4 CH 2	4-MeOC 6 H 4
1725	3-MeOC 6 H 4 CH 2	4-MeOC 6 H 4
1726	4-MeOC 6 H 4 CH 2	4-MeOC 6 H 4
1727	3,4-diMeOC 6 H 4 CH 2	4-MeOC 6 H 4
1728	2,5-diMeOC 6 H 4 CH 2	4-MeOC 6 H 4
1729	Methyl	2-MeOC 6 H 4
1730	Methyl	3,4-diMeOC 6 H 4
1731	3,4-(OCH 2 O)C 6 H 4 CH 2	4-MeOC 6 H 4
1732	3-thiophenylCH 2	4-MeOC 6 H 4
1733	2-MeOC 6 H 4 CH 2	4-MeOC 6 H 4
1734	3,4-diClOC 6 H 4 CH 2	4-MeOC 6 H 4
1735	2,4-diClOC 6 H 4 CH 2	4-MeOC 6 H 4
1736	2-ClC 6 H 4 CH 2	4-MeOC 6 H 4
1737	H 2 NCH 2	4-MeOC 6 H 4
1738	HOCH 2 NHCH 2 CH 2	4-MeOC 6 H 4
1739	Me 2 NCH 2	4-MeOC 6 H 4
1740	PiperazinylCH 2	4-MeOC 6 H 4
1741	4-Me-piperazinylCH 2	4-MeOC 6 H 4
1742	4-HOCH 2 CH 2 -piperazinylCH 2	4-MeOC 6 H 4
1743	PiperidinylCH 2	4-MeOC 6 H 4
1744	4-NH 2 CH 2 -piperidinylCH 2	4-MeOC 6 H 4
1745	CH 3 CH 2 NHCH 2	4-MeOC 6 H 4
1746	ThiomorpholinylCH 2	4-MeOC 6 H 4
1747	MorpholinylCH 2	4-MeOC 6 H 4
1748	PyyrolidinylCH 2	4-MeOC 6 H 4
1749	4-pyridylCH 2 NHCH 2	4-MeOC 6 H 4
1750	4-CH 3 CONHC 6 H 4 CH 2	4-MeOC 6 H 4
1751	4-CH 3 OCONHC 6 H 4 CH 2	4-MeOC 6 H 4
1752	4-NH 2 CH 2 CONHC 6 H 4 CH 2	4-MeOC 6 H 4
1753	4-Me 2 NCH 2 CONHC 6 H 4 CH 2	4-MeOC 6 H 4
1754	4-N 3 C 6 H 4 CH 2	4-MeOC 6 H 4
1755	4-NH 2 C 6 H 4 CH 2	4-MeOC 6 H 4
1756	C 6 H 5 NH	4-MeOC 6 H 4
1757	CH 3 CH 2 CH 2 NH	4-MeOC 6 H 4
1758	4-NH 2 C 6 H 4 CH 2 NH	4-MeOC 6 H 4
1759	4-pyridyCH 2 NH	4-MeOC 6 H 4
1760	Methyl	4-HOC 6 H 4
1761	H	4-MeOC 6 H 4
1762	Methyl	3-pyridyl
1763	Methyl	4-pyridyl
1764	H	4-pyridyl
1765	Methyl	C 6 H 5
1766	Methyl	4-MeSC 6 H 4
1767	Methyl	4-MeSO 2 C 6 H 4
1768	Methyl	4-Me 2 NC 6 H 4
1769	MorpholinylCH 2	4-Me 2 NC 6 H 4
1770	Me 2 NCH 2	4-Me 2 NC 6 H 4
1771	Me 2 NCH 2	4-(piperdinyl)C 6 H 4
1772	Me 2 NCH 2	4-(morpholinyl)C 6 H 4
1773	Me 2 NCH 2	4-CH 3 CH 2 OC 6 H 4
1774	Me 2 NCH 2	4-CH 3 CH 2 CH 2 CH 2 C 6 H 4
1775	Me 2 NCH 2	4-CH 3 CH 2 C 6 H 4
1776	Me 2 NCH 2	4-CH 3 CH 2 CH 2 C 6 H 4

Claims

1. A compound according to the formula: or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:X is selected from the group consisting of O and S; R1 is NHR4; R4 is NR3R3a; R3a is H or C1-4 alkyl; R3 is COR5; R5 is phenyl; and R2 is phenyl substituted with C1-4 alkoxy.

2. A compound according to claim 1, wherein the compound is 3-(4-methoxyphenyl)-5-(2-benzoylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one.

3. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of the following formula: or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:X is selected from the group consisting of O and S; R1 is NHR4; R4 is NR3R3a; R3a is H or C1-4 alkyl; R3 is COR5; R5 is phenyl; and R2 is phenyl substituted with C1-4 alkoxy.

4. A method of treating cancer and proliferative diseases comprising: administering to a host in need of such treatment a therapeutically effective amount of a compound of the following formula: or a pharmaceutically acceptable salt or prodrug form thereof, wherein:X is selected from the group consisting of O and S; R1 is NHR4; R4 is NR3R3a; R3a is H or C1-4 alkyl; R3 is COR5; R5 is phenyl; and R2 is phenyl substituted with C1-4 alkoxy.