Hydrazonopyrazole derivatives and their use as therapeutics

Abstract

Pharmaceutical compositions and compounds are provided. The compounds of the invention demonstrate anti-proliferative activity, and may promote apoptosis in cells lacking normal regulation of cell cycle and death. In one embodiment of the invention, pharmaceutical compositions of the compounds in combination with a physiologically acceptable carrier are provided. The pharmaceutical compositions are useful in the treatment of hyperproliferative disorders, which disorders include tumor growth, lymphoproliferative diseases, angiogenesis. The compounds of the invention are substituted pyrazoles and pyrazolines.

1 - 150 . (canceled) 
     
     
         151 . A pharmaceutical composition comprising a pharmaceutically excipient and a compound of formula (Ic): 
       
         
           
           
               
               
           
         
         as a single tautomer, a mixture of tautomers, a single stereoisomer, a mixture of stereoisomers, or a racemic mixture; or a pharmaceutically acceptable salt or solvate thereof; 
         wherein: 
         R 1c  is hydrogen, alkyl, aryl or aralkyl; 
         R 2c  is aryl optionally substituted with one or more substituents selected from the group consisting of halo, alkoxy, nitro, haloalkyl, —R 6c —N(R 8c ) 2 , —S(O) 2 —R 6c —OH, —S(O) 2 —N(R 7c )R 8c  and heterocyclylalkyl; 
         or R 2c  is N-heterocyclyl optionally substituted one or more substituents selected from the group consisting of alkyl, halo, and —C(O)OR 7c ; 
         R 4c  is hydrogen or alkyl; 
         R 3c  is hydrogen, alkyl, heterocyclylalkyl, or heterocyclylcarbonyl; 
         R 5c  is hydrogen, alkyl, alkenyl, —R 6c —O—R 12c , —R 6c —S—R 12c , —R 6c —N(R 9c ) 2 , cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl and aryl), aryl (optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halo, haloalkyl, haloalkoxy, haloalkylthio, arylthioalkyl (wherein the aryl group is optionally substituted with one or more halo groups), nitro, —C(O)OR 7c , and —N(R 7c )—C(O)—R 7c ), aralkyl (wherein the aryl group is optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halo, haloalkyl, haloalkoxy, haloalkylthio, arylthioalkyl (wherein the aryl group is optionally substituted with one or more halo groups), nitro, —C(O)OR 7c , and —N(R 7c )—C(O)—R 7c ), aralkenyl (wherein the aryl group is optionally substituted by one or more halo groups), heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, alkyl thio, and aryl (optionally substituted with one or more halo groups)), or heterocyclylalkyl; 
         each R 6c  is independently a straight or branched alkylene chain; 
         each R 7c  is independently hydrogen, alkyl, aryl, aralkyl or heterocyclylalkyl; 
         R 8c  is hydrogen, alkyl, aryl aralkyl or hydroxyalkyl; 
         each R 9c  is independently hydrogen, heterocyclylalkyl, —C(O)—R 1 —C(O)—R 10c —C(O)OR 7c , C(O)OR 7c , or —S(O) 2 —R 7c ; 
         each R 10c  is independently a direct bond, straight or branched alkylene chain or straight or branched alkenylene chain; 
         R 11c  is aryl (optionally substituted by one or more substituents selected from the group consisting of alkyl and halo), heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, —C(O)OR 7c  and —C(O)N(R 7c ) 2 ) or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of —C(O)OR 7c  and —C(O)N(R 7c ) 2 ); and 
         each R 12c  is independently methyl, aryl or aralkyl (optionally substituted by one or more substituents selected from group consisting of halo and nitro), 
         provided that when R 1c , R 3c , R 4c  and R 5c  are all hydrogen, R 2c  cannot be unsubstituted phenyl and when R 1c , R 3c  and R 4c  are all hydrogen and R 5c  is methyl, R 2c  cannot be phenyl optionally substituted with one or more substituents selected from the group consisting of chloro, bromo or alkyl. 
       
     
     
         152 . The pharmaceutical composition of  claim 151  wherein the compound is a compound of formula (Ic) wherein:
 R 1c  and R 4c  are each hydrogen; 
 R 2c  is aryl optionally substituted with one or more substituents selected from the group consisting of halo, alkoxy, nitro, haloalkyl, —R 6c —N(R 8c ) 2 , —S(O) 2 —R 6c —OH, —S(O) 2 —N(R 7c )R 8c  and heterocyclylalkyl; and 
 R 5c  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halo, haloalkyl, haloalkoxy, haloalkylthio, arylthioalkyl (wherein the aryl group is optionally substituted with one or more halo groups), nitro, —C(O)OR 7c , and —N(R 7c )—C(O)—R 7c . 
 
     
     
         153 . The pharmaceutical composition of  claim 152  wherein the compound is a compound of formula (Ic) selected from the group consisting of the following:
 5-phenyl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-m-tolyl-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-p-tolyl-4H-pyrazol-3-ylamine; 
 5-(3-chlorophenyl)-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylamine; 
 5-(4-chlorophenyl)-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-(3-trifluoromethylphenyl)-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-(4-trifluoromethoxyphenyl)-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-(4-methoxyphenyl)-4H-pyrazol-3-ylamine; 
 (2-morpholin-4-ylethyl)[5-phenyl-4-(phenylhydrazono)-4H-pyrazol-3-yl]amine; 
 N-[5-phenyl-4-(phenylhydrazono)-4H-pyrazol-3-yl]nicotinamide; 
 5-(2-fluorophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3,4-dimethoxyphenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-yl}benzoic acid; 
 5-(2-nitrophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(4-chloro-3-nitrophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3-fluorophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(4-nitrophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3-nitrophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3-bromophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(4-fluoro-3-methylphenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(4-fluorophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3,4-difluorophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3-fluoro-4-methylphenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3,4-dimethylphenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-(2-trifluoromethoxyphenyl)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-(4-trifluoromethylsulfanylphenyl)-4H-pyrazol-3-ylamine; 
 5-(3,5-difluorophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-(4-trifluoromethylphenyl)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-(3,4,5-trimethoxyphenyl)-4H-pyrazol-3-ylamine; 
 5-[3-(4-chlorophenylsulfanylmethyl)phenyl]-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 N-{4-[5-amino-4-(phenylhydrazono)-4H-pyrazol-3-yl]phenyl}acetamide; 
 4-[(3-Fluorophenyl)hydrazono]-5-phenyl-4H-pyrazol-3-ylamine; 
 4-{5-Amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-yl}benzoic acid methyl ester; and 
 5-(3-Nitrophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine. 
 
     
     
         154 . The pharmaceutical composition of  claim 151  wherein the compound is a compound of formula (Ic) wherein:
 R 2c  is phenyl optionally substituted with one or more substituents selected from the group consisting of halo, alkoxy, nitro, haloalkyl, —R 6c —N(R 8c ) 2 , —S(O) 2 —R 6c —OH, —S(O) 2 —N(R 7c )R 8c  and heterocyclylalkyl; and 
 R 5c  is aralkyl (wherein the aryl group is optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halo, haloalkyl, haloalkoxy, haloalkylthio, arylthioalkyl (wherein the aryl group is optionally substituted with one or more halo groups), aralkenyl (wherein the aryl group is optionally substituted by one or more halo groups), or heterocyclylalkyl selected from the group consisting isoindoledionylalkyl, morpholinylalkyl, and triazolylalkyl. 
 
     
     
         155 . The pharmaceutical composition of  claim 154  wherein the compound is a compound of formula (Ic) selected from the group consisting of the following:
 5-(4-methoxybenzyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-phenethyl-4H-pyrazol-3-ylamine; 
 4-[(3-chlorophenyl)hydrazono]-5-phenethyl-4H-pyrazol-3-ylamine; 
 4-[(3,5-difluorophenyl)hydrazono]-5-phenethyl-4H-pyrazol-3-ylamine; 
 5-(4-chlorobenzyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-benzhydryl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(2,5-dimethoxy-benzyl)-4-(phenyl-hydrazono)-4H-pyrazol-3-ylamine; 
 5-(3,4-dimethoxybenzyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-phenethyl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3-ethyl-benzyl)-4-(phenyl-hydrazono)-4H-pyrazol-3-ylamine; 
 2-{5-amino-4-[(3,4-difluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}isoindole-1,3-dione; 
 2-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}isoindole-1,3-dione; 
 4-[(3-fluorophenyl)hydrazono]-5-morpholin-4-ylmethyl-4H-pyrazol-3-ylamine; 
 4-[(3,4-difluorophenyl)hydrazono]-5-morpholin-4-ylmethyl-4H-pyrazol-3-ylamine; 
 5-(1-methyl-1-[1,2,4]triazol-1-ylethyl)-4-(phenylhydrazono)-4H-pyrazol-3-yl-amine; 
 5-(2-morpholin-4-ylethyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-(3-morpholin-4-yl-propyl)-4H-pyrazol-3-ylamine; and 
 5-(4-morpholin-4-ylbutyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine. 
 
     
     
         156 . The pharmaceutical composition of  claim 151  wherein the compound is a compound of formula (Ic) wherein:
 R 2c  is phenyl (optionally substituted with one or more substituents selected from the group consisting of halo, alkoxy, nitro, haloalkyl, —R 6c —N(R 8c ) 2 , —S(O) 2 —R 6c —OH, —S(O) 2 —N(R 7c )R 8c  and heterocyclylalkyl); and 
 R 5c  is heterocyclyl selected from the group consisting of piperidinyl, morpholinyl, pyrrolidinyl, furanyl, isooxazolyl, pyridinyl, thienyl, pyrrolyl, quinolinyl, benzothienyl, benzodioxolyl, benzooxadiazolyl, pyrazolyl, thiadiazolyl, and quinoxalinyl, wherein the heterocycle is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, alkylthio, and aryl (optionally substituted with one or more halo groups). 
 
     
     
         157 . The pharmaceutical composition of  claim 156  wherein the compound is a compound of formula (Ic) selected from the group consisting of the following:
 4-[(3-fluorophenyl)hydrazono]-5-furan-2-yl-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-(2-methylfuran-3-yl)-4H-pyrazol-3-ylamine; 
 5-(2,5-dimethyl-furan-3-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-pyridin-4-yl-4H-pyrazol-3-ylamine; 
 5-(2-chloro-6-methylpyridin-4-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3,5-dimethylisoxazol-4-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(1-methyl-1H-pyrrol-2-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-thiophen-3-yl-4H-pyrazol-3-ylamine; 
 5-(5-methyl-2-trifluoromethylfuran-3-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(2-tert-butyl-5-methylfuran-3-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(2-methylfuran-3-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-furan-2-yl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-quinolin-6-yl-4H-pyrazol-3-ylamine; 
 5-[5-(4-chlorophenyl)-2-methylfuran-3-yl]-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-benzo[b]thiophen-3-yl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 2-{3-[N′-(3-amino-5-pyridin-4-yl-pyrazol-4-ylidene)hydrazino]benzenesulfonyl}-ethanol; 
 4-[(3-fluorophenyl)hydrazono]-5-pyridin-4-yl-4H-pyrazol-3-ylamine; 
 4-[N′-(3-amino-5-pyridin-4-ylpyrazol-4-ylidene)hydrazino]benzenesulfonamide; 
 5-(2-chloropyridin-4-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-benzo[1,3]dioxol-5-yl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-benzo[1,2,5]oxadiazol-5-yl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(5-bromopyridin-3-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-[(3-morpholin-4-ylmethylphenyl)hydrazono]-5-pyridin-4-yl-4H-pyrazol-3-ylamine; 
 4-[(3-fluoro-4-methoxyphenyl)hydrazono]-5-pyridin-4-yl-4H-pyrazol-3-ylamine; 
 5-(2-methylsulfanylpyridin-3-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(6-chloropyridin-3-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-benzo[b]thiophen-2-yl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 1′-phenyl-4-(phenylhydrazono)-5′-propyl-4H,1′H-[3,4′]bipyrazolyl-5-ylamine; 
 5-(4-methyl-[1,2,3]thiadiazol-5-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-quinoxalin-2-yl-4H-pyrazol-3-ylamine; 
 2′,5′-dimethyl-4-(phenylhydrazono)-4H,2′H-[3,3]bipyrazolyl-5-ylamine; 
 5-(5-methyl-3-phenylisoxazol-4-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-[(3,4-difluorophenyl)hydrazono]-5-pyridin-4-yl-4H-pyrazol-3-ylamine; 
 4-[(3,4-difluoro-phenyl)-hydrazono]-5-pyridin-3-yl-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-pyridin-3-yl-4H-pyrazol-3-ylamine; 
 5-(3-chlorothiophen-2-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 {4-[(3-fluorophenyl)hydrazono]-5-pyridin-4-yl-4H-pyrazol-3-yl}methylamine; 
 {4-[(3,4-difluorophenyl)hydrazono]-5-pyridin-4-yl-4H-pyrazol-3-yl}-methylamine; 
 4-(phenylhydrazono)-5-thiophen-2-yl-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-pyridin-2-yl-4H-pyrazol-3-ylamine; 
 5-(3-methoxythiophen-2-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-morpholin-4-yl-4-(phenyl-hydrazono)-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-morpholin-4-yl-4H-pyrazol-3-ylamine; 
 4-{N′-[3-amino-5-(4-methylpiperazin-1-yl)-pyrazol-4-ylidene]-hydrazino}-benzenesulfonamide; 
 4-[N′-(3-amino-5-pyrrolidin-1-yl-pyrazol-4-ylidene)-hydrazino]-benzenesulfonamide; 
 5-(4-methylpiperazin-1-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine dihydrochloride; 
 5-pyrrolidin-1-yl-4-[(3-trifluoromethyl-phenyl)-hydrazono]-4H-pyrazol-3-ylamine; 
 3-[N′-(3-amino-5-pyrrolidin-1-yl-pyrazol-4-ylidene)-hydrazino]-N-methyl-benzenesulfonamide; 
 3-[N′-(3-amino-5-pyrrolidin-1-yl-pyrazol-4-ylidene)-hydrazino]-benzenesulfonamide; 
 4-[(3-fluoro-phenyl)-hydrazono]-5-pyrrolidin-1-yl-4H-pyrazol-3-ylamine; 
 5-pyrrolidin-1-yl-4-[(3-pyrrolidin-1-ylmethyl-phenyl)-hydrazono]-4H-pyrazol-3-ylamine; 
 4-[(3-dimethylaminomethylphenyl)-hydrazono]-5-morpholin-4-yl-4H-pyrazol-3-ylamine; 
 4-[(3-morpholin-4-ylmethyl-phenyl)-hydrazono]-5-pyrrolidin-1-yl-4H-pyrazol-3-ylamine; 
 4-[(3-fluoro-4-methoxyphenyl)-hydrazono]-5-morpholin-4-yl-4H-pyrazol-3-ylamine; 
 3-[N′-(3-amino-5-morpholin-4-yl-pyrazol-4-ylidene)-hydrazino]-benzenesulfonamide; 
 3-[N′(3-amino-5-morpholin-4-yl-pyrazol-4-ylidene)-hydrazino]-N-methyl-benzenesulfonamide; and 
 3-[N′-(3-amino-5-morpholin-4-yl-pyrazol-4-ylidene)-hydrazino]-N-(2-hydroxyethyl)-benzenesulfonamide. 
 
     
     
         158 . The pharmaceutical composition of  claim 151  wherein the compound is a compound of formula (Ic) wherein:
 R 1c  and R 4c  are each hydrogen; 
 R 2c  is phenyl optionally substituted with one or more substituents selected from the group consisting of halo, alkoxy, nitro, haloalkyl, —R 6c —N(R 8c ) 2 , —S(O) 2 —R 6c —OH, —S(O) 2 —N(R 7c )R 8c  and heterocyclylalkyl; and 
 R 5c  is —R 6c —O—R 12c , —R 6 —S—R 12c , or —R 6c —N(R 9c ) 2 . 
 
     
     
         159 . The pharmaceutical composition of  claim 158  wherein the compound is a compound of formula (Ic) selected from the group consisting of the following:
 5-(4-chlorophenoxymethyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3-phenoxypropyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(2-methylsulfanylethyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(2-nitrophenoxymethyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-aminomethyl-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylamine; 
 3-({5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}carbamoyl)-acrylic acid; 
 N-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-isonicotinamide; 
 N-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-nicotinamide; 
 1-[({5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-carbamoyl)methyl]-pyrrolidine-2-carboxylic acid methyl ester; 
 1-[3-({5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-carbamoyl)acryloyl]-pyrrolidine-2-carboxylic acid methyl ester; 
 N-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-methanesulfonamide; 
 N-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-succinamic acid; 
 1-[({5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-carbamoyl)methyl]-pyrrolidine-2-carboxylic acid; 
 N-{5-amino-4-[(3,4-difluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-nicotinamide; 
 4-[(3,4-difluorophenyl)-hydrazono]-5-[(2-morpholin-4-ylethylamino)methyl]-4H-pyrazol-3-yl-amine; 
 N-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-4-fluorobenzenesulfonamide; 
 N-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}malonamic acid benzyl ester; 
 butane-1-sulfonic acid {5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}amide; 
 N-{5-amino-4-[(3,4-difluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-2-chloro-6-methyl-nicotinamide; 
 N-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-2-chloro-6-methyl-nicotinamide; 
 5-(3-aminopropyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-{[bis-(2-morpholin-4-ylethyl)amino]methyl}-4-[(3,4-difluorophenyl)-hydrazono]-4H-pyrazol-3-ylamine; 
 5-[(bis-pyridin-3-ylmethylamino)methyl]-4-[(3,4-difluorophenyl)hydrazono]-4H-pyrazol-3-ylamine; 
 5-[(bis-pyridin-2-ylmethylamino)methyl]-4-[(3,4-difluorophenyl)hydrazono]-4H-pyrazol-3-ylamine; 
 5-Aminomethyl-4-[(3,4-difluorophenyl)hydrazono]-4H-pyrazol-3-ylamine; and 
 ({5-amino-4-[(3,4-difluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}ethoxy-carbonylmethylamino)acetic acid ethyl ester. 
 
     
     
         160 . The pharmaceutical composition of  claim 151  wherein the compound is a compound of formula (Ic) wherein:
 R 1c  and R 4c  are each hydrogen; 
 R 2c  is N-heterocyclyl selected from the group consisting of pyridinyl, thiazolyl, tetrazolyl, pyrazolyl, isoquinolinyl, quinolinyl, and phthalazinyl, wherein the N-heterocyclyl is optionally substituted one or more substituents selected from the group consisting of alkyl, halo, and —C(O)OR 7c ; 
 R 3c  is hydrogen or alkyl; and 
 R 5c  is hydrogen, alkyl, alkenyl, —R 6c —NH 2 , cycloalkyl, phenylalkyl (wherein the phenyl group is optionally substituted by one or more substituents selected from the group consisting of alkoxy and halo), or heterocyclyl selected from the group consisting of morpholin-4-yl, piperidin-4-yl, pyridin-4-yl, thien-2-yl, pyrrolyl, and pyrrolidin-1-yl, or phenyl (optionally substituted by one or more substituents selected from the group consisting of alkoxy and halo). 
 
     
     
         161 . The pharmaceutical composition of  claim 160  wherein the compound is a compound of formula (Ic) selected from the group consisting of the following:
 5-methyl-4-[(4H-[1,2,4]triazol-3-yl)hydrazono]-4H-pyrazol-3-ylamine; 
 5-methyl-4-[(2H-tetrazol-5-yl)hydrazono]-4H-pyrazol-3-ylamine; 
 3-[N′-(3-amino-5-methylpyrazol-4-ylidene)hydrazino]-1H-pyrazole-4-carboxylic acid ethyl ester; 
 3-[N′-(3-amino-5-methylpyrazol-4-ylidene)hydrazino]-1H-pyrazole-4-carboxylic acid; 
 5-[N′-(3-amino-5-methylpyrazol-4-ylidene)hydrazino]-2H-[1,2,3]triazole-4-carboxylic acid; 
 5-(4-methoxybenzyl)-4-(pyridin-3-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-tert-butyl-4-[(1H-tetrazol-5-yl)hydrazono]-4H-pyrazol-3-ylamine; 
 4-(isoquinolin-5-ylhydrazono)-5-phenethyl-4H-pyrazol-3-ylamine; 
 5-but-3-enyl-4-(isoquinolin-5-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-aminomethyl-4-(isoquinolin-5-ylhydrazono)-4H-pyrazol-3-ylamine; 
 4-(isoquinolin-5-ylhydrazono)-5-methyl-4H-pyrazol-3-ylamine; 
 5-methyl-4-(pyridin-3-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-but-3-enyl-4-(quinolin-6-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-but-3-enyl-4-(pyridin-3-ylhydrazono)-4H-pyrazol-3-ylamine; 
 ethyl-[5-methyl-4-(pyridin-3-ylhydrazono)-4H-pyrazol-3-yl]amine; 
 4-(isoquinolin-5-ylhydrazono)-5-pyridin-4-yl-4H-pyrazol-3-ylamine; 
 5-pyridin-4-yl-4-(pyridin-3-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-methyl-4-(phthalazin-5-ylhydrazono)-4H-pyrazol-3-ylamine; 
 methyl-[4-(phthalazin-5-ylhydrazono)-5-pyridin-4-yl-4H-pyrazol-3-yl]amine; 
 4-(pyridin-3-yl-hydrazono)-5-thiophen-2-yl-4H-pyrazol-3-ylamine; 
 5-(1-methyl-1H-pyrrol-2-yl)-4-(pyridin-3-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(1-methyl-1H-pyrrol-2-yl)-4-(quinolin-6-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-cyclopropyl-4-(pyridin-3-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-morpholin-4-yl-4-(pyridin-3-yl-hydrazono)-4H-pyrazol-3-ylamine; 
 4-[(6-chloropyridin-3-yl)-hydrazono]-5-morpholin-4-yl-4H-pyrazol-3-ylamine; 
 5-pyrrolidin-1-yl-4-(quinolin-6-yl-hydrazono)-4H-pyrazol-3-ylamine; 
 4-[(6-chloro-pyridin-3-yl)-hydrazono]-5-pyrrolidin-1-yl-4H-pyrazol-3-ylamine; 
 4-[(6-fluoro-pyridin-3-yl)-hydrazono]-5-pyrrolidin-1-yl-4H-pyrazol-3-ylamine; 
 5-morpholin-4-yl-4-(phthalazin-5-yl-hydrazono)-4H-pyrazol-3-ylamine; 
 4-[(6-methyl-pyridin-3-yl)-hydrazono]-5-morpholin-4-yl-4H-pyrazol-3-ylamine; 
 4-(Phthalazin-5-yl-hydrazono)-5-pyridin-4-yl-4H-pyrazol-3-ylamine; and 
 5-(2-fluorophenyl)-4-(phthalazin-5-ylhydrazono)-4H-pyrazol-3-ylamine. 
 
     
     
         162 . A compound of formula (Ic): 
       
         
           
           
               
               
           
         
         as a single tautomer, a mixture of tautomers, a single stereoisomer, a mixture of stereoisomers, or a racemic mixture; or a pharmaceutically acceptable salt or solvate thereof; 
         wherein: 
         R 1c  is hydrogen, alkyl, aryl or aralkyl; 
         R 2c  is aryl optionally substituted with one or more substituents selected from the group consisting of halo, alkoxy, nitro, haloalkyl, —R 6c —N(R 8c ) 2 , —S(O) 2 —R 6c —OH, —S(O) 2 —N(R 7c )R 8c  and heterocyclylalkyl; 
         R 3c  is hydrogen, alkyl, heterocyclylalkyl, or heterocyclylcarbonyl; 
         R 4c  is hydrogen or alkyl; 
         R 5c  is aryl optionally substituted by one or more substituents selected from the group consisting of alkoxy, halo, haloalkyl, haloalkoxy, haloalkylthio, arylthioalkyl (wherein the aryl group is optionally substituted with one or more halo groups), nitro, —C(O)OR 7c , and —N(R 7c )—C(O)—R 7c ; or 
         R 5c  is aralkyl (wherein the aryl group is optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halo, haloalkyl, haloalkoxy, haloalkylthio, and arylthioalkyl (wherein the aryl group is optionally substituted with one or more halo groups)) or aralkenyl (wherein the aryl group is optionally substituted by one or more halo groups); or 
         R 5c  is heterocyclyl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, alkylthio, and aryl (optionally substituted with one or more halo groups); or 
         R 5c  is heterocyclylalkyl selected from the group consisting of the following: isoindoledionylalkyl, morpholinylalkyl, and triazolylalkyl; or 
         R 5c  is —R 6c —O—R 12c , —R 6c —S—R 12c , —R 6c —N(R 9c ) 2 ; 
         R 6c  is a straight or branched alkylene chain; 
         each R 7c  is independently hydrogen, alkyl, aryl, aralkyl or heterocyclylalkyl; and 
         R 8c  is hydrogen, alkyl, aryl, aralkyl or hydroxyalkyl. 
         each R 9c  is independently hydrogen, alkyl, aryl, aralkyl, heterocyclylalkyl, —C(O)—R 11c , —C(O)—R 10c —C(O)OR 7c , —R 10c —C(O)OR 7c , or —S(O) 2 —R 7c ; 
         each R 10c  is independently a direct bond, straight or branched alkylene chain or straight or branched alkenylene chain; 
         R 11c  is aryl (optionally substituted by one or more substituents selected from the group consisting of alkyl and halo), heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, —C(O)OR 7c  and —C(O)N(R 7c ) 2 ) or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of —C(O)OR 7c  and —C(O)N(R 7c ) 2 ); and 
         each R 12c  is independently methyl, aryl or aralkyl (optionally substituted by one or more substituents selected from group consisting of halo and nitro) 
         provided that when R 1c , R 3c  and R 4c  are all hydrogen and R 2c  is unsubstituted phenyl, R 5c  cannot be unsubstituted benzyl, and 
         provided that when R 1c , R 3c , and R 4c  is hydrogen, and R 2c  is unsubstituted phenyl, R 5c  cannot be pyrazolonyl, benzothiazolyl or thioxotriazinyl. 
       
     
     
         163 . The compound of  claim 162  wherein:
 R 1c  and R 4c  are each hydrogen; and 
 R 5c  is phenyl optionally substituted by one or more substituents selected from the group consisting of alkoxy, halo, haloalkyl, haloalkoxy, haloalkylthio, phenylthioalkyl (wherein the phenyl group is optionally substituted with one or more halo groups), nitro, —C(O)OR 7c , and —N(R 7c )—C(O)—R 7c . 
 
     
     
         164 . The compound of  claim 163  selected from the group consisting of the following:
 5-phenyl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-m-tolyl-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-p-tolyl-4H-pyrazol-3-ylamine; 
 5-(3-chlorophenyl)-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylamine; 
 5-(4-chlorophenyl)-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-(3-trifluoromethylphenyl)-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-(4-trifluoromethoxyphenyl)-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-(4-methoxyphenyl)-4H-pyrazol-3-ylamine; 
 (2-morpholin-4-ylethyl)[5-phenyl-4-(phenylhydrazono)-4H-pyrazol-3-yl]amine; 
 N-[5-phenyl-4-(phenylhydrazono)-4H-pyrazol-3-yl]nicotinamide; 
 5-(2-fluorophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3,4-dimethoxyphenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-yl}benzoic acid; 
 5-(2-nitrophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(4-chloro-3-nitrophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3-fluorophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(4-nitrophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3-nitrophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3-bromophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(4-fluoro-3-methylphenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(4-fluorophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3,4-difluorophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3-fluoro-4-methylphenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3,4-dimethylphenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-(2-trifluoromethoxyphenyl)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-(4-trifluoromethylsulfanylphenyl)-4H-pyrazol-3-ylamine; 
 5-(3,5-difluorophenyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-(4-trifluoromethylphenyl)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-(3,4,5-trimethoxyphenyl)-4H-pyrazol-3-ylamine; 
 5-[3-(4-chlorophenylsulfanylmethyl)phenyl]-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; and 
 N-{4-[5-amino-4-(phenylhydrazono)-4H-pyrazol-3-yl]phenyl}acetamide. 
 
     
     
         165 . The compound of  claim 162  wherein:
 R 1c  and R 4c  are each hydrogen; 
 R 2c  is phenyl optionally substituted with one or more substituents selected from the group consisting of halo, alkoxy, nitro, haloalkyl, —R 6c —N(R 8c ) 2 , —S(O) 2 —R 6c —OH, —S(O) 2 —N(R 7c )R 8c  and heterocyclylalkyl; and 
 R 5c  is phenylalkyl (wherein the phenyl group is optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halo, haloalkyl, haloalkoxy, haloalkylthio, phenylthioalkyl (wherein the phenyl group is optionally substituted with one or more halo groups) or phenylalkenyl (wherein the phenyl group is optionally substituted by one or more halo groups). 
 
     
     
         166 . The compound of  claim 165  selected from the group consisting of the following:
 5-(4-methoxybenzyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-phenethyl-4H-pyrazol-3-ylamine; 
 4-[(3-chlorophenyl)hydrazono]-5-phenethyl-4H-pyrazol-3-ylamine; 
 4-[(3,5-difluorophenyl)hydrazono]-5-phenethyl-4H-pyrazol-3-ylamine; 
 5-(4-chlorobenzyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-benzhydryl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(2,5-dimethoxy-benzyl)-4-(phenyl-hydrazono)-4H-pyrazol-3-ylamine; 
 5-(3,4-dimethoxybenzyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-phenethyl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; and 
 5-(3-ethyl-benzyl)-4-(phenyl-hydrazono)-4H-pyrazol-3-ylamine. 
 
     
     
         167 . The compound of  claim 162  wherein R 5c  is a heterocyclyl selected from the group consisting of piperidinyl, morpholinyl, pyrrolidinyl, furanyl, isooxazolyl, pyridinyl, thienyl, pyrrolyl, quinolinyl, benzothienyl, benzodioxolyl, benzooxadiazolyl, pyrazolyl, thiadiazolyl, and quinoxalinyl. 
     
     
         168 . The compound of  claim 167  selected from the group consisting of the following:
 4-[(3-fluorophenyl)hydrazono]-5-furan-2-yl-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-(2-methylfuran-3-yl)-4H-pyrazol-3-ylamine; 
 5-(2,5-dimethyl-furan-3-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-pyridin-4-yl-4H-pyrazol-3-ylamine; 
 5-(2-chloro-6-methylpyridin-4-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3,5-dimethylisoxazol-4-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(1-methyl-1H-pyrrol-2-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-thiophen-3-yl-4H-pyrazol-3-ylamine; 
 5-(5-methyl-2-trifluoromethylfuran-3-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(2-tert-butyl-5-methylfuran-3-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(2-methylfuran-3-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-furan-2-yl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-quinolin-6-yl-4H-pyrazol-3-ylamine; 
 5-[5-(4-chlorophenyl)-2-methylfuran-3-yl]-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-benzo[b]thiophen-3-yl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 2-{3-[N-(3-amino-5-pyridin-4-yl-pyrazol-4-ylidene)hydrazino]benzenesulfonyl}-ethanol; 
 4-[(3-fluorophenyl)hydrazono]-5-pyridin-4-yl-4H-pyrazol-3-ylamine; 
 4-[N-(3-amino-5-pyridin-4-ylpyrazol-4-ylidene)hydrazino]benzenesulfonamide; 
 5-(2-chloropyridin-4-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-benzo[1,3]dioxol-5-yl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-benzo[1,2,5]oxadiazol-5-yl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(5-bromopyridin-3-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-[(3-morpholin-4-ylmethylphenyl)hydrazono]-5-pyridin-4-yl-4H-pyrazol-3-ylamine; 
 4-[(3-fluoro-4-methoxyphenyl)hydrazono]-5-pyridin-4-yl-4H-pyrazol-3-ylamine; 
 5-(2-methylsulfanylpyridin-3-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(6-chloropyridin-3-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-benzo[b]thiophen-2-yl-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 1′-phenyl-4-(phenylhydrazono)-5′-propyl-4H,1′H-[3,4′]bipyrazolyl-5-ylamine; 
 5-(4-methyl-[1,2,3]thiadiazol-5-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-quinoxalin-2-yl-4H-pyrazol-3-ylamine; 
 2′,5′-dimethyl-4-(phenylhydrazono)-4H,2′H-[3,3′]bipyrazolyl-5-ylamine; 
 5-(5-methyl-3-phenylisoxazol-4-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-[(3,4-difluorophenyl)hydrazono]-5-pyridin-4-yl-4H-pyrazol-3-ylamine; 
 4-[(3,4-difluoro-phenyl)-hydrazono]-5-pyridin-3-yl-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-pyridin-3-yl-4H-pyrazol-3-ylamine; 
 5-(3-chlorothiophen-2-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 {4-[(3-fluorophenyl)hydrazono]-5-pyridin-4-yl-4H-pyrazol-3-yl}methylamine; 
 {4-[(3,4-difluorophenyl)hydrazono]-5-pyridin-4-yl-4H-pyrazol-3-yl}methylamine; 
 4-(phenylhydrazono)-5-thiophen-2-yl-4H-pyrazol-3-ylamine; 
 4-(phenylhydrazono)-5-pyridin-2-yl-4H-pyrazol-3-ylamine; 
 5-(3-methoxythiophen-2-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-morpholin-4-yl-4-(phenyl-hydrazono)-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-morpholin-4-yl-4H-pyrazol-3-ylamine; 
 4-{N′-[3-amino-5-(4-methylpiperazin-1-yl)-pyrazol-4-ylidene]-hydrazino}-benzenesulfonamide; 
 4-[N′-(3-amino-5-pyrrolidin-1-yl-pyrazol-4-ylidene)-hydrazino]-benzenesulfonamide; 
 5-(4-methylpiperazin-1-yl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine dihydrochloride; 
 5-pyrrolidin-1-yl-4-[(3-trifluoromethyl-phenyl)-hydrazono]-4H-pyrazol-3-ylamine; 
 3-[N′-(3-amino-5-pyrrolidin-1-yl-pyrazol-4-ylidene)-hydrazino]-N-methyl-benzenesulfonamide; 
 3-[N′-(3-amino-5-pyrrolidin-1-yl-pyrazol-4-ylidene)-hydrazino]-benzenesulfonamide; 
 4-[(3-fluoro-phenyl)-hydrazono]-5-pyrrolidin-1-yl-4H-pyrazol-3-ylamine; 
 5-pyrrolidin-1-yl-4-[(3-pyrrolidin-1-ylmethyl-phenyl)-hydrazono]-4H-pyrazol-3-ylamine; 
 4-[(3-dimethylaminomethylphenyl)-hydrazono]-5-morpholin-4-yl-4H-pyrazol-3-ylamine; 
 4-[(3-morpholin-4-ylmethyl-phenyl)-hydrazono]-5-pyrrolidin-1-yl-4H-pyrazol-3-ylamine; 
 4-[(3-fluoro-4-methoxyphenyl)-hydrazono]-5-morpholin-4-yl-4H-pyrazol-3-ylamine; 
 3-[N′-(3-amino-5-morpholin-4-yl-pyrazol-4-ylidene)-hydrazino]-benzenesulfonamide; 
 3-[N′-(3-amino-5-morpholin-4-yl-pyrazol-4-ylidene)-hydrazino]-N-methyl-benzenesulfonamide; and 
 3-[N′-(3-amino-5-morpholin-4-yl-pyrazol-4-ylidene)-hydrazino]-N-(2-hydroxyethyl)-benzenesulfonamide. 
 
     
     
         169 . The compound of  claim 162  selected from the group consisting of the following:
 2-{5-amino-4-[(3,4-difluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}isoindole-1,3-dione; 
 2-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}isoindole-1,3-dione; 
 4-[(3-fluorophenyl)hydrazono]-5-morpholin-4-ylmethyl-4H-pyrazol-3-ylamine; 
 4-[(3,4-difluorophenyl)hydrazono]-5-morpholin-4-ylmethyl-4H-pyrazol-3-ylamine; 
 5-(1-methyl-1-[1,2,4]triazol-1-ylethyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(2-morpholin-4-ylethyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 4-[(3-fluorophenyl)hydrazono]-5-(3-morpholin-4-yl-propyl)-4H-pyrazol-3-ylamine; and 
 5-(4-morpholin-4-ylbutyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine. 
 
     
     
         170 . The compound of  claim 162  wherein:
 R 1c  and R 4c  are each hydrogen; 
 R 5c  is —R 6c —O—R 12c —, —R 6c —S—R 12c , —R 6c —N(R 9c ) 2 ; and 
 R 2c  is phenyl (optionally substituted with one or more substituents selected from the group consisting of halo, alkoxy, nitro, haloalkyl, —R 6c —N(R 8c ) 2 , —S(O) 2 —R 6c —OH, —S(O) 2 —N(R 7c )R 8c  and heterocyclylalkyl). 
 
     
     
         171 . The compound of  claim 170  selected from the group consisting of the following:
 5-(4-chlorophenoxymethyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(3-phenoxypropyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(2-methylsulfanylethyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(2-nitrophenoxymethyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-aminomethyl-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylamine; 
 3-({5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}carbamoyl)-acrylic acid; 
 N-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-isonicotinamide; 
 N-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-nicotinamide; 
 1-[({5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-carbamoyl)methyl]-pyrrolidine-2-carboxylic acid methyl ester; 
 1-[3-({5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-carbamoyl)acryloyl]-pyrrolidine-2-carboxylic acid methyl ester; 
 N-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-methanesulfonamide; 
 N-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-succinamic acid; 
 1-[({5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-carbamoyl)methyl]pyrrolidine-2-carboxylic acid; 
 N-{5-amino-4-[(3,4-difluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-nicotinamide; 
 4-[(3,4-difluorophenyl)-hydrazono]-5-[(2-morpholin-4-ylethylamino)methyl]-4H-pyrazol-3-yl-amine; 
 N-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-4-fluorobenzenesulfonamide; 
 N-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-malonamic acid benzyl ester; 
 butane-1-sulfonic acid {5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}amide; 
 N-{5-amino-4-[(3,4-difluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-2-chloro-6-methyl-nicotinamide; 
 N-{5-amino-4-[(3-fluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-2-chloro-6-methyl-nicotinamide; 
 5-(3-aminopropyl)-4-(phenylhydrazono)-4H-pyrazol-3-ylamine; 
 5-{[bis-(2-morpholin-4-ylethyl)amino]methyl}-4-[(3,4-difluorophenyl)-hydrazono]-4H-pyrazol-3-yl-amine; 
 5-[(bis-pyridin-3-ylmethylamino)methyl]-4-[(3,4-difluorophenyl)-hydrazono]-4H-pyrazol-3-ylamine; 
 5-[(bis-pyridin-2-ylmethylamino)methyl]-4-[(3,4-difluorophenyl)-hydrazono]-4H-pyrazol-3-ylamine; and 
 ({5-amino-4-[(3,4-difluorophenyl)hydrazono]-4H-pyrazol-3-ylmethyl}-ethoxycarbonyl-methylamino)acetic acid ethyl ester. 
 
     
     
         172 . A compound of formula (Ic): 
       
         
           
           
               
               
           
         
         as a single tautomer, a mixture of tautomers, a single stereoisomer, a mixture of stereoisomers, or a racemic mixture; or a pharmaceutically acceptable salt or solvate thereof; 
         wherein: 
         R 1c  is hydrogen, alkyl, aryl or aralkyl; 
         R 2c  is N-heterocyclyl (optionally substituted one or more substituents selected from the group consisting of alkyl, halo and —C(O)OR 7c ); 
         R 3c  is hydrogen, alkyl, aryl, aralkyl, heterocyclylalkyl, or heterocyclylcarbonyl; 
         R 4c  is hydrogen or alkyl; 
         R 5c  is hydrogen, alkyl, alkenyl, —R 6c —O—R 12c , —R 6c —S—R 12c , —R 6c —N(R 9c ) 2 , cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl and aryl), aryl (optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halo, haloalkyl, haloalkoxy, haloalkylthio, arylthioalkyl (wherein the aryl group is optionally substituted with one or more halo groups), nitro, —C(O)OR 7c , and —N(R 7c )—C(O)—R 7c ), aralkyl (wherein the aryl group is optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halo, haloalkyl, haloalkoxy, haloalkylthio, arylthioalkyl (wherein the aryl group is optionally substituted with one or more halo groups), nitro, —C(O)OR 7c , and —N(R 7c )—C(O)—R 7c ), aralkenyl (wherein the aryl group is optionally substituted by one or more halo groups), heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, alkylthio, and aryl (optionally substituted with one or more halo groups)), or heterocyclylalkyl; 
         each R 6c  is independently a straight or branched alkylene chain; 
         each R 7c  is independently hydrogen, alkyl, aryl, aralkyl or heterocyclylalkyl; 
         each R 9c  is independently hydrogen, alkyl, aryl, aralkyl, heterocyclylalkyl, —C(O)—R 11c , —C(O)—R 10c —C(O)OR 7c , —R 10c —C(O)OR 7c , or —S(O) 2 —R 7c ; 
         each R 10c  is independently a direct bond, straight or branched alkylene chain or straight or branched alkenylene chain; 
         R 11c  is aryl (optionally substituted by one or more substituents selected from the group consisting of alkyl and halo), heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of —C(O)OR 7c  and —C(O)N(R 7c ) 2 ) or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of —C(O)OR 7c  and —C(O)N(R 7c ) 2 ); and 
         each R 12c  is independently methyl, aryl or aralkyl (optionally substituted by one or more substituents selected from group consisting of halo and nitro); 
         provided that when R 1c , R 3c , R 4c  and R 5c  are all hydrogen, R 2c  cannot be thiadiazolyl; and when R 1c , R 3c  and R 4c  are all hydrogen, R 2c  and R 5c  cannot be both pyrazolonyl; and when R 1c , R 3c  and R 4c  are all hydrogen, and R 5c  is methyl, R 2c  cannot be optionally substituted pyrazolyl; and when R 1c , R 3c  and R 4c  are all hydrogen, and R 5c  is t-butyl, R 2c  cannot be pyridin-3-yl optionally substituted with chloro. 
       
     
     
         173 . The compound of  claim 172  wherein:
 R 1c  and R 4c  are each hydrogen; 
 R 2c  is N-heterocyclyl selected from the group consisting of pyridinyl, thiazolyl, tetrazolyl, pyrazolyl, isoquinolinyl, quinolinyl, and phthalazinyl; 
 R 3c  is hydrogen or alkyl; and 
 R 5c  is hydrogen, alkyl, alkenyl, —R 6c —NH 2 , cycloalkyl, phenylalkyl (wherein the phenyl group is optionally substituted by one or more substituents selected from the group consisting of alkoxy and halo), heterocyclyl selected from the group consisting of pyridin-4-yl, thien-2-yl, pyrrol-2-yl, morpholin-4-yl, and pyrrolidin-1-yl, or phenyl (optionally substituted by one or more substituents selected from the group consisting of alkoxy and halo). 
 
     
     
         174 . The compound of  claim 173  selected from the group consisting of the following:
 5-methyl-4-[(4H-[1,2,4]triazol-3-yl)hydrazono]-4H-pyrazol-3-ylamine; 
 5-methyl-4-[(2H-tetrazol-5-yl)hydrazono]-4H-pyrazol-3-ylamine; 
 3-[N′-(3-amino-5-methylpyrazol-4-ylidene)hydrazino]-1H-pyrazole-4-carboxylic acid ethyl ester; 
 3-[N′-(3-amino-5-methylpyrazol-4-ylidene)hydrazino]-1H-pyrazole-4-carboxylic acid; 
 5-[N′-(3-amino-5-methylpyrazol-4-ylidene)hydrazino]-2H-[1,2,3]triazole-4-carboxylic acid; 
 5-(4-methoxybenzyl)-4-(pyridin-3-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-tert-butyl-4-[(1H-tetrazol-5-yl)hydrazono]-4H-pyrazol-3-ylamine; 
 4-(isoquinolin-5-ylhydrazono)-5-phenethyl-4H-pyrazol-3-ylamine; 
 5-but-3-enyl-4-(isoquinolin-5-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-aminomethyl-4-(isoquinolin-5-ylhydrazono)-4H-pyrazol-3-ylamine; 
 4-(isoquinolin-5-ylhydrazono)-5-methyl-4H-pyrazol-3-ylamine; 
 5-methyl-4-(pyridin-3-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-but-3-enyl-4-(quinolin-6-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-but-3-enyl-4-(pyridin-3-ylhydrazono)-4H-pyrazol-3-ylamine; 
 ethyl-[5-methyl-4-(pyridin-3-ylhydrazono)-4H-pyrazol-3-yl]amine; 
 4-(isoquinolin-5-ylhydrazono)-5-pyridin-4-yl-4H-pyrazol-3-ylamine; 
 5-pyridin-4-yl-4-(pyridin-3-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-methyl-4-(phthalazin-5-ylhydrazono)-4H-pyrazol-3-ylamine; 
 methyl-[4-(phthalazin-5-ylhydrazono)-5-pyridin-4-yl-4H-pyrazol-3-yl]amine; 
 4-(pyridin-3-yl-hydrazono)-5-thiophen-2-yl-4H-pyrazol-3-ylamine; 
 5-(1-methyl-1H-pyrrol-2-yl)-4-(pyridin-3-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-(1-methyl-1H-pyrrol-2-yl)-4-(quinolin-6-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-cyclopropyl-4-(pyridin-3-ylhydrazono)-4H-pyrazol-3-ylamine; 
 5-morpholin-4-yl-4-(pyridin-3-yl-hydrazono)-4H-pyrazol-3-ylamine; 
 4-[(6-chloropyridin-3-yl)-hydrazono]-5-morpholin-4-yl-4H-pyrazol-3-ylamine; 
 5-pyrrolidin-1-yl-4-(quinolin-6-yl-hydrazono)-4H-pyrazol-3-ylamine; 
 4-[(6-chloro-pyridin-3-yl)-hydrazono]-5-pyrrolidin-1-yl-4H-pyrazol-3-ylamine; 
 4-[(6-fluoro-pyridin-3-yl)-hydrazono]-5-pyrrolidin-1-yl-4H-pyrazol-3-ylamine; 
 5-morpholin-4-yl-4-(phthalazin-5-yl-hydrazono)-4H-pyrazol-3-ylamine; 
 4-[(6-methyl-pyridin-3-yl)-hydrazono]-5-morpholin-4-yl-4H-pyrazol-3-ylamine; and 
 5-(2-fluorophenyl)-4-(phthalazin-5-ylhydrazono)-4H-pyrazol-3-ylamine.