Pharmaceutically acceptable salts of 3,5-diaminopyrazole kinase inhibitors

Abstract

Provided herein are pharmaceutically acceptable salts of 3,5-diaminopyrazoles, for example, pharmaceutically acceptable salts of compounds of Formula IA, that are useful for modulating regulated-in-COPD kinase activity, and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a RC kinase-mediated disorder, disease, or condition.

What is claimed is: 
     
         1 . A method for the treatment, prevention, or amelioration of one or more symptoms of a RC kinase-mediated disorder, disease, or condition in a subject, which comprises administering to the subject acetic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, formic acid, hydrobromic acid, hydrochloric acid, methanesulfonic acid, oxalic acid, phosphoric acid, sulfuric acid, tartaric acid, p-toluenesulfonic acid, or trifluoroacetic acid salt of a compound of Formula IA: 
       
         
           
           
               
               
           
         
         or a stereoisomer, enantiomer, mixture of enantiomers, mixture of diastereomers, or isotopic variant thereof; or a pharmaceutically acceptable solvate, hydrate, or prodrug thereof; wherein:
 R 1  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 2  is C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 3  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; 
 R 4  is cyano, aminocarbonyl, —C(O)N═CR 4a R 4b , or —C(O)NR 4a R 4b ; wherein:
 R 4a  is C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; and 
 R 4b  is independently hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )R 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; 
 
 R 5  is —N(R 5e )CR 5a R 5c R 5d ; wherein:
 R 5a  is C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 5c  and R 5d  are each independently hydrogen, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; and 
 R 5e  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; and 
 
 each R 1a , R 1b , R 1c , and R 1d  is independently hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; or R 1a  and R 1c  together with the C and N atoms to which they are attached form heterocyclyl; or R 1b  and R 1c  together with the N atom to which they are attached form heterocyclyl; 
 wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substituted with one or more substituents Q, where each Q is independently selected from (a) oxo, cyano, halo, nitro, and pentafluorosulfanyl; (b) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclyl-C 1-6  alkyl, each of which is further optionally substituted with one or more substituents Q a ; and (c) —B(R a )OR d , —B(OR a )OR d , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR 1a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , and —S(O) 2 NR b R c , wherein each R a , R b , R c , and R d  is independently (i) hydrogen; (ii) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclyl-C 1-6  alkyl, each optionally substituted with one or more substituents Q a ; or (iii) R b  and R c  together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q a ; 
 wherein each Q a  is independently selected from the group consisting of (a) oxo, cyano, halo, nitro, and pentafluorosulfanyl; (b) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclyl-C 1-6  alkyl; and (c) —B(R e )OR g , —B(OR e )OR g , —C(O)R e , —C(O)OR e , —C(O)NR f R g , —C(NR e )NR f R g , —OR e , —OC(O)R e , —OC(O)OR e , —OC(O)NR f R g , —OC(═NR e )NR f R g , —OS(O)R e , —OS(O) 2 R e , —OS(O)NR f R g , —OS(O) 2 NR f R g , —NR f R g , —NR e C(O)R h , —NR e C(O)OR f , —NR e C(O)NR f R g , —NR e C(═NR h )NR f R g , —NR e S(O)R h , —NR e S(O) 2 R h , —NR e S(O)NR f R g , —NR e S(O) 2 NR f R g , —P(O)R e R h , —P(O)(OR e )R h , —P(O)(OR e )(OR h ), —SR e , —S(O)R e , —S(O) 2 R e , —SF 5 , —S(O)NR f R g , and —S(O) 2 NR f R g ; wherein each R e , R f , R g , and R h  is independently (i) hydrogen; (ii) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclyl-C 1-6  alkyl; or (iii) R f  and R g  together with the N atom to which they are attached form heterocyclyl. 
 
       
     
     
         2 . The method of  claim 1 , having the structure of Formula I: 
       
         
           
           
               
               
           
         
         or a stereoisomer, enantiomer, mixture of enantiomers, mixture of diastereomers, or isotopic variant thereof; or a pharmaceutically acceptable solvate, hydrate, or prodrug thereof. 
       
     
     
         3 . The method of  claim 1 , having the structure of Formula XIII: 
       
         
           
           
               
               
           
         
         or a stereoisomer, enantiomer, mixture of enantiomers, mixture of diastereomers, or isotopic variant thereof; or a pharmaceutically acceptable solvate, hydrate, or prodrug thereof. 
       
     
     
         4 . The method of  claim 1 , wherein R 2  is C 3-10  cycloalkyl, C 6-14  aryl, or heteroaryl, each of which is optionally substituted with one, two, three, four, or five substituents Q. 
     
     
         5 . The method of  claim 1 , wherein R 2  is C 3-10  cycloalkyl, optionally substituted with one or more substituents Q. 
     
     
         6 . The method of  claim 1 , wherein R 2  is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl, each of which is optionally substituted with one or more substituents Q. 
     
     
         7 . The method of  claim 1 , wherein R 2  is cyclopropyl or cyclohexyl, each of which is optionally substituted with one or more substituents Q. 
     
     
         8 . The method of  claim 1 , wherein R 2  is heteroaryl, optionally substituted with one or more substituents Q. 
     
     
         9 . The method of  claim 8 , wherein R 2  is 5- or 6-membered heteroaryl, each of which is optionally substituted with one or more substituents Q. 
     
     
         10 . The method of  claim 8 , wherein R 2  is pyridinyl, optionally substituted with one or more substituents Q. 
     
     
         11 . The method of  claim 1 , wherein R 2  is C 3-10  cycloalkyl, C 6-14  aryl, or heteroaryl, each of which is optionally substituted with one, two, three, four, or five substituents Q, wherein each substituent Q is independently selected from cyano, nitro, halo, heteroaryl, heterocyclyl, C 1-6  alkyl, and C 1-6  alkoxy, where the alkyl and alkoxy are each optionally substituted with one or more substituents Q a . 
     
     
         12 . The method of  claim 11 , wherein each substituent Q is independently selected from cyano, nitro, chloro, methyl, butyl, methoxy, 4-methylpiperazin-1-yl, morpholinomethyl, morpholino, pyridin-2-yl, 4-isopropylpiperazin-1-yl, and 1H-imidazol-1-yl. 
     
     
         13 . The method of  claim 1 , wherein R 2  is cyclopropyl, cyclohexyl, phenyl, pyridinyl or 1H-indazol-5-yl, each of which is optionally substituted with one, two, three, four, or five substituents Q. 
     
     
         14 . The method of  claim 13 , wherein each substituent Q is independently selected from cyano, nitro, halo, heteroaryl, heterocyclyl, C 1-6  alkyl, and C 1-6  alkoxy, where the alkyl and alkoxy are each optionally substituted with one or more substituents Q a . 
     
     
         15 . The method of  claim 13 , wherein each substituent Q is independently selected from cyano, nitro, chloro, methyl, butyl, methoxy, 4-methylpiperazin-1-yl, morpholinomethyl, morpholino, pyridin-2-yl, 4-isopropylpiperazin-1-yl, and 1H-imidazol-1-yl. 
     
     
         16 . The method of  claim 13 , wherein R 2  is cyclopropyl, cyclohexyl, phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 2,3,4,5-tetrachlorophenyl, 4-cyanophenyl, 4-nitrophenyl, 4-t-butylphenyl, 3,5-dimethylphenyl, 4-methoxyphenyl, pyridin-3-yl, 4-(4-methylpiperazin-1-yl)phenyl, 4-(morpholinomethyl)phenyl, 4-morpholinophenyl, 4-(pyridin-2-yl)phenyl, 4-(4-isopropylpiperazin-1-yl)phenyl, or 4-(1H-imidazol-1-yl)phenyl. 
     
     
         17 . The method of  claim 1 , wherein R 2  is C 6-14  aryl, optionally substituted with one or more substituents Q. 
     
     
         18 . The method of  claim 17 , having the structure of Formula IV: 
       
         
           
           
               
               
           
         
         or a stereoisomer, enantiomer, mixture of enantiomers, mixture of diastereomers, or isotopic variant thereof; or a pharmaceutically acceptable solvate, hydrate, or prodrug thereof; wherein:
 each R 6  is independently (a) cyano, halo, or nitro; (b) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more substituents Q; or (c) —B(R 1a )OR 1d , —B(OR 1a )OR 1d , —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —OR 1a , —OC(O)R 1a , —OC(O)OR 1a , —OC(O)NR 1b R 1c , —OC(═NR 1a )NR 1b R 1c , —OS(O)R 1a , —OS(O) 2 R 1a , —OS(O)NR 1b R 1c , —OS(O) 2 NR 1b R 1c , —NR 1b R 1c , —NR 1a C(O)R 1d , —NR 1a C(O)OR 1d , —NR 1a C(O)NR 1b R 1c , —NR 1a C(═NR d )NR 1b R 1c , —NR 1a S(O)R 1d , —NR 1a S(O) 2 R 1d , —NR 1a S(O)NR 1b R 1c , —NR 1a S(O) 2 NR 1b R 1c , —SR 1a , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; and 
 n is an integer of 0, 1, 2, 3, 4, or 5. 
 
       
     
     
         19 . The method of  claim 18 , having the structure of Formula XV: 
       
         
           
           
               
               
           
         
         or a stereoisomer, enantiomer, mixture of enantiomers, mixture of diastereomers, or isotopic variant thereof; or a pharmaceutically acceptable solvate, hydrate, or prodrug thereof. 
       
     
     
         20 . The method of  claim 1 , wherein R 5c  is hydrogen. 
     
     
         21 . The method of  claim 1 , wherein R 5d  is hydrogen. 
     
     
         22 . The method of  claim 1 , wherein R 5a  is C 6-14  aryl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more substituents Q. 
     
     
         23 . The method of  claim 1 , wherein R 5a  is C 6-14  aryl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one, two, three, four, or five substituents Q, wherein each substituent Q is independently selected from (a) halo, cyano, nitro, and pentafluorosulfanyl; (b) C 1-6  alkyl, C 6-14  aryl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more substituents Q; and (c) —B(R 1a )OR 1d , —C(O)R 1a , —C(O)OR 1a , —OR 1a , —NR 1b R 1c , and —S(O) 2 R 1a . 
     
     
         24 . The method of  claim 23 , wherein each substituent Q is independently selected from fluoro, chloro, bromo, cyano, nitro, pentafluorosulfanyl, methyl, trifluoromethyl, hydroxymethyl, phenylthiomethyl, phenyl, fluorophenyl, chlorophenyl, thienyl, triazolyl, pyridinyl, benzimidazolyl, methylpiperazinyl, tetrahydropyrrolyl, morpholinyl, hydroxyl, methoxy, difluoromethoxy, trifluoromethoxy, fluorobenzyloxy, chlorothiazolylmethoxy, pyrimidinyloxy, trifluoromethylpyrimidinyloxy, trifluoromethylpyridinyloxy, hydroxyethoxy, hydroxycarbonylmethoxy, amino, dimethylamino, hydroxyboryl, acetyl, benzyloxycarbonyl, methylsulfonyl, and phenylsulfonyl. 
     
     
         25 . The method of  claim 22 , wherein R 5a  is C 6-14  aryl, optionally substituted with one or more substituents Q. 
     
     
         26 . The method of  claim 25 , wherein R 5a  is phenyl or naphthyl, each of which is optionally substituted with one or more substituents Q. 
     
     
         27 . The method of  claim 22 , wherein R 5a  is heteroaryl, optionally substituted with one or more substituents Q. 
     
     
         28 . The method of  claim 27 , wherein R 5a  is furanyl pyrrolyl, thienyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, pyridinyl, pyrazinyl, indolyl, benzimidazolyl, benzo[d][1,2,3]thiadiazolyl, or 4H-benzo[d][1,3]dioxinyl, each of which is optionally substituted with one or more substituents Q. 
     
     
         29 . The method of  claim 22 , wherein R 5a  is heterocyclyl, optionally substituted with one or more substituents Q. 
     
     
         30 . The method of  claim 29 , wherein R 5a  is tetrahydropyrrolyl, piperidinyl, or piperazinyl, each of which is optionally substituted with one or more substituents Q. 
     
     
         31 . The method of  claim 22 , wherein R 5a  is phenyl, naphthyl, furanyl pyrrolyl, thienyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, pyridinyl, pyrazinyl, indolyl, benzimidazolyl, benzo[d][1,2,3]thiadiazolyl, 4H-benzo[d][1,3]dioxinyl, tetrahydropyrrolyl, piperidinyl, or piperazinyl, each of which is optionally substituted with one, two, three, four, or five substituents Q. 
     
     
         32 . The method of  claim 31 , wherein each substituent Q is independently selected from (a) halo, cyano, nitro, and pentafluorosulfanyl; (b) C 1-6  alkyl, C 6-14  aryl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more substituents Q; and (c) —B(R 1a )OR 1d , —C(O)R 1a , —C(O)OR 1a , —OR 1a , —NR 1b R 1c , and —S(O) 2 R 1a . 
     
     
         33 . The method of  claim 31 , wherein each substituent Q is independently selected from fluoro, chloro, bromo, cyano, nitro, pentafluorosulfanyl, methyl, trifluoromethyl, hydroxymethyl, phenylthiomethyl, phenyl, fluorophenyl, chlorophenyl, thienyl, triazolyl, pyridinyl, benzimidazolyl, methylpiperazinyl, tetrahydropyrrolyl, morpholinyl, hydroxyl, methoxy, difluoromethoxy, trifluoromethoxy, fluorobenzyloxy, chlorothiazolylmethoxy, pyrimidinyloxy, trifluoromethylpyrimidinyloxy, trifluoromethylpyridinyloxy, hydroxyethoxy, hydroxycarbonylmethoxy, amino, dimethylamino, hydroxyboryl, acetyl, benzyloxycarbonyl, methylsulfonyl, and phenylsulfonyl. 
     
     
         34 . The method of  claim 22 , wherein R 5a  is (i) phenyl or naphth-1-yl; (ii) 4-chlorophenyl, 4-cyanophenyl, 4-nitrophenyl, 4-pentafluorosulfanylphenyl, 4-trifluoromethylphenyl, 2-thien-2-ylphenyl, 4-(4H-1,2,4-triazol-4-yl)phenyl, 4-pyridin-2-ylphenyl, 4-(benzimidazol-1-yl)phenyl, 4-(4-methylpiperazin-1-yl)phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3-(2-hydroxyethoxy)phenyl, 4-(2-hydroxyethoxy)phenyl, 4-(4-fluorobenzyloxy)phenyl, 3-(pyrimidin-2-yloxy)phenyl, 2-hydroxyphenyl, 4-hydroxyphenyl, 4-(pyrimidin-2-yloxy)phenyl, 4-(4-trifluoromethylpyrimidin-2-yloxy)phenyl, 4-(5-trifluoromethylpyridin-2-yloxy)phenyl, 4-(pyrimidin-2-yloxy)phenyl, 4-(5-trifluoromethylpyridin-2-yloxy)phenyl, 2-(hydroxycarbonylmethoxy)phenyl, or 4-methylsulfonylphenyl; (iii) 2-fluoro-6-chlorophenyl, 4-fluoro-3-cyanophenyl, 4-fluoro-2-methylphenyl, 4-fluoro-2-hydroxyphenyl, 5-fluoro-2-methoxyphenyl, 3-fluoro-4-methoxyphenyl, 5-fluoro-2-methoxyphenyl, 3-fluoro-4-trifluoromethoxy-phenyl, 2,4-dichlorophenyl, 2-chloro-6-hydroxyphenyl, 4-chloro-2-hydroxyphenyl, 5-chloro-2-hydroxyphenyl, 5-bromo-2-hydroxyphenyl, 2-nitro-5-hydroxyphenyl, 3-nitro-4-hydroxyphenyl, 4-nitro-3-hydroxyphenyl, 5-nitro-2-hydroxyphenyl, 3-nitro-4-methoxyphenyl, 5-trifluoromethyl-2-methoxyphenyl, 2-hydroxy-4-methylphenyl, 2,4-dihydroxyphenyl, 2,5-dihydroxyphenyl, 2-hydroxy-3-methoxyphenyl, 2-hydroxy-4-methoxyphenyl, 2-hydroxy-6-methoxyphenyl, 4-hydroxy-3-methoxyphenyl, 3-hydroxy-4-difluoromethoxyphenyl, 3-methoxy-4-(2-chlorothiazol-5-ylmethoxy)phenyl, or 5-(hydroxyboryl)-2-methoxyphenyl; (iv) 3,5-difluoro-4-hydroxyphenyl, 2,4-dichloro-6-hydroxyphenyl, 2,3-dimethyl-4-methoxyphenyl, 4-hydroxy-3,5-dimethylphenyl, 4-hydroxy-2,6-dimethylphenyl, 4-hydroxy-3,5-dimethylphenyl, 2,4,6-trihydroxyphenyl, 3-hydroxy-4,5-dimethoxyphenyl, or 4-hydroxy-5-methoxy-3-dimethylaminophenyl; (v) 5-(4-chlorophenyl)furan-2-yl, 5-(hydroxymethyl)furan-2-yl, pyrrol-2-yl, pyrrol-3-yl, 1-phenylsulfonylpyrrol-2-yl, thien-2-yl, 2-(pyridin-2-yl)thien-5-yl, 3-(4-fluorophenyl)pyrazol-4-yl, 3-chloro-5-trifluoromethylpyrazol-4-yl, 1-methyl-3-phenylthiomethyl-5-chloropyrazol-4-yl, 1-methyl-3-trifluoromethyl-5-chloropyrazol-4-yl, 3-(4-fluorophenyl)pyrazol-4-yl, imidazol-4-yl, 2-ethyl-5-methylimidazol-4-yl, 2-phenyl-5-chloroimidazol-4-yl, 5-methylisoxazol-5-yl, 2-chloro-thiazol-5-yl, 2-aminothiazol-5-yl, 4-methylthiazol-5-yl, 2-tetrahydropyrrol-1-ylpyridin-3-yl, 3-tetrahydropyrrol-1-ylpyridin-5-yl, 2-(morpholin-4-yl)pyridin-5-yl, 2-chloropyridin-3-yl, 2-chloropyridin-5-yl, 2-chloropyridin-6-yl, 3-fluoropyridin-2-yl, 2-methoxypyridin-5-yl, pyrazin-2-yl, 3,5-dichloropyrazin-2-yl, benzo[d][1,2,3]thiadiazol-5-yl, 2-methylindol-3-yl, 1-methyl-2-chloroindol-3-yl, 4,5,6,7-tetrafluoroindol-3-yl, 6-fluoro-4H-benzo[d][1,3]dioxin-8-yl, or benzimidazol-2-yl; or (vi) 1-(benzyloxycarbonyl)tetrahydropyrrol-2-yl, piperidin-4-yl, 1-methylsulfonylpiperidin-4-yl, or 4-acetylpiperazin-1-yl. 
     
     
         35 . The method of  claim 1 , wherein R 3  is hydrogen. 
     
     
         36 . The method of  claim 1 , wherein R 1  is hydrogen. 
     
     
         37 . The method of a  claim 1 , wherein R 4  is CN. 
     
     
         38 . The method of  claim 1 , wherein R 4  is aminocarbonyl. 
     
     
         39 . The method of  claim 1 , wherein R 4  is —C(O)N═CR 4a R 4b . 
     
     
         40 . The method of  claim 39 , wherein R 4b  is hydrogen. 
     
     
         41 . The method of  claim 39 , wherein R 4a  is C 6-14  aryl, optionally substituted with one or more substitutents Q. 
     
     
         42 . The method of  claim 41 , wherein R 4a  is phenyl, optionally substituted with one or more substitutents Q. 
     
     
         43 . The method of  claim 41 , wherein R 4a  is methoxyphenyl. 
     
     
         44 . The method of  claim 1 , wherein the salt is an acetic acid salt. 
     
     
         45 . The method of  claim 1 , wherein the salt is a formic acid salt. 
     
     
         46 . The method of  claim 1 , wherein the salt is a camphorsulfonic acid salt. 
     
     
         47 . The method of  claim 1 , wherein the salt is a hydrobromic acid salt. 
     
     
         48 . The method of  claim 1 , wherein the salt is a hydrochloric acid salt. 
     
     
         49 . The method of  claim 1 , wherein the salt is a methanesulfonic acid salt. 
     
     
         50 . The method of  claim 1 , wherein the salt is a phosphoric acid salt. 
     
     
         51 . The method of  claim 1 , wherein the salt is a sulfuric acid salt. 
     
     
         52 . The method of  claim 1 , wherein the salt is a tartaric acid salt. 
     
     
         53 . The method of  claim 1 , wherein the salt is a p-toluenesulfonic acid salt. 
     
     
         54 . The method of  claim 1 , wherein the salt is a trifluoroacetic acid salt. 
     
     
         55 . The method of  claim 1 , wherein the salt is selected from the group consisting of:
 3-((3-chlorophenyl)amino)-5-((4-hydroxybenzyl)amino)-3h-pyrazole-4-carboxamide hydrochloride;   5-((4-hydroxybenzyl)amino)-3-((4-(4-methylpiperazin-1-yl)phenyl)amino)-3h-pyrazole-4-carboxamide hydrochloride;   5-((4-hydroxybenzyl)amino)-3-((4-(morpholinomethyl)phenyl)amino)-3h-pyrazole-4-carboxamide hydrochloride;   5-((4-hydroxybenzyl)amino)-3-((4-morpholinophenyl)amino)-3h-pyrazole-4-carboxamide hydrobromide;   5-((4-hydroxybenzyl)amino)-3-((4-morpholinophenyl)amino)-3h-pyrazole-4-carboxamide hydrochloride;   5-((4-hydroxybenzyl)amino)-3-((4-morpholinophenyl)amino)-3h-pyrazole-4-carboxamide, acetic acid salt;   5-((4-hydroxybenzyl)amino)-3-((4-morpholinophenyl)amino)-3h-pyrazole-4-carboxamide, formic acid salt;   5-((4-hydroxybenzyl)amino)-3-((4-morpholinophenyl)amino)-3h-pyrazole-4-carboxamide, camphorsulfonic acid salt;   5-((4-hydroxybenzyl)amino)-3-((4-morpholinophenyl)amino)-3h-pyrazole-4-carboxamide, phosphoric acid salt;   5-((4-hydroxybenzyl)amino)-3-((4-morpholinophenyl)amino)-3h-pyrazole-4-carboxamide, sulfuric acid salt;   5-((4-hydroxybenzyl)amino)-3-((4-morpholinophenyl)amino)-3h-pyrazole-4-carboxamide, trifluoroacetic acid salt;   5-((4-hydroxybenzyl)amino)-3-((4-morpholinophenyl)amino)-3h-pyrazole-4-carboxamide, tartaric acid salt;   5-((4-hydroxybenzyl)amino)-3-((6-morpholinopyridin-3-yl)amino)-3h-pyrazole-4-carboxamide hydrochloride;   5-((4-hydroxybenzyl)amino)-3-((6-morpholinopyridin-3-yl)amino)-3h-pyrazole-4-carboxamide, methanesulfonic acid salt;   5-((4-hydroxybenzyl)amino)-3-((6-morpholinopyridin-3-yl)amino)-3h-pyrazole-4-carboxamide, phosphoric acid salt;   5-((4-hydroxybenzyl)amino)-3-((6-morpholinopyridin-3-yl)amino)-3h-pyrazole-4-carboxamide, sulfuric acid salt;   5-((4-hydroxybenzyl)amino)-3-((6-morpholinopyridin-3-yl)amino)-3h-pyrazole-4-carboxamide, trifluoroacetic acid salt;   5-((4-hydroxybenzyl)amino)-3-((4-(pyridin-2-yl)phenyl)amino)-3h-pyrazole-4-carboxamide, camphorsulfonic acid salt;   5-((4-hydroxybenzyl)amino)-3-((4-(pyridin-2-yl)phenyl)amino)-3h-pyrazole-4-carboxamide, phosphoric acid salt;   5-((4-hydroxybenzyl)amino)-3-((4-(pyridin-2-yl)phenyl)amino)-3h-pyrazole-4-carboxamide, sulfuric acid salt;   5-((4-hydroxybenzyl)amino)-3-((4-(pyridin-2-yl)phenyl)amino)-3h-pyrazole-4-carboxamide, tartaric acid salt;   5-((4-hydroxybenzyl)amino)-3-((4-(pyridin-2-yl)phenyl)amino)-3h-pyrazole-4-carboxamide, p-toluenesulfonic acid salt;   5-((4-hydroxybenzyl)amino)-3-((4-(pyridin-2-yl)phenyl)amino)-3h-pyrazole-4-carboxamide, trifluoroacetic acid salt;   5-((4-hydroxybenzyl)amino)-3-((4-(4-isopropylpiperazin-1-yl)phenyl)amino)-3h-pyrazole-4-carboxamide hydrochloride;   5-((4-hydroxybenzyl)amino)-3-((4-(4-isopropylpiperazin-1-yl)phenyl)amino)-3h-pyrazole-4-carboxamide, phosphoric acid salt;   3-((4-(1h-imidazol-1-yl)phenyl)amino)-5-((4-hydroxybenzyl)amino)-3h-pyrazole-4-carboxamide hydrochloride;   3-((4-(1h-imidazol-1-yl)phenyl)amino)-5-((4-hydroxybenzyl)amino)-3h-pyrazole-4-carboxamide, acetic acid salt;   3-((4-(1h-imidazol-1-yl)phenyl)amino)-5-((4-hydroxybenzyl)amino)-3h-pyrazole-4-carboxamide, phosphoric acid salt and   3-((1h-indazol-5-yl)amino)-5-((4-hydroxybenzyl)amino)-3h-pyrazole-4-carboxamide hydrochloride;   
       and stereoisomers, enantiomers, mixtures of enantiomers, mixtures of diastereomers, and isotopic variants thereof; and pharmaceutically acceptable solvates, hydrates, and prodrugs thereof. 
     
     
         56 . A method for the treatment, prevention, or amelioration of one or more symptoms of an eosinophil-related disorder, disease, or condition in a subject, which comprises administering to the subject acetic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, formic acid, hydrobromic acid, hydrochloric acid, methanesulfonic acid, oxalic acid, phosphoric acid, sulfuric acid, tartaric acid, p-toluenesulfonic acid, or trifluoroacetic acid salt of a compound of Formula IA: 
       
         
           
           
               
               
           
         
         or a stereoisomer, enantiomer, mixture of enantiomers, mixture of diastereomers, or isotopic variant thereof; or a pharmaceutically acceptable solvate, hydrate, or prodrug thereof; wherein:
 R 1  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 2  is C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 3  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; 
 R 4  is cyano, aminocarbonyl, —C(O)N═CR 4a R 4b , or —C(O)NR 4a R 4b ; wherein:
 R 4a  is C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; and 
 R 4b  is independently hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )R 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; 
 
 R 5  is —N(R 5e )CR 5a R 5c R 5d ; wherein:
 R 5a  is C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 5c  and R 5d  are each independently hydrogen, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; and 
 R 5e  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; and 
 
 each R 1a , R 1b , R 1c , and R 1d  is independently hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; or R 1a  and R 1c  together with the C and N atoms to which they are attached form heterocyclyl; or R 1b  and R 1c  together with the N atom to which they are attached form heterocyclyl; 
 wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substituted with one or more substituents Q, where each Q is independently selected from (a) oxo, cyano, halo, nitro, and pentafluorosulfanyl; (b) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclyl-C 1-6  alkyl, each of which is further optionally substituted with one or more substituents Q a ; and (c) —B(R a )OR d , —B(OR a )OR d , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR 1a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , and —S(O) 2 NR b R c , wherein each R a , R b , R e , and R d  is independently (i) hydrogen; (ii) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclyl-C 1-6  alkyl, each optionally substituted with one or more substituents Q a ; or (iii) R b  and R c  together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q a ; 
 wherein each Q a  is independently selected from the group consisting of (a) oxo, cyano, halo, nitro, and pentafluorosulfanyl; (b) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclyl-C 1-6  alkyl; and (c) —B(R e )OR g , —B(OR e )OR g , —C(O)R e , —C(O)OR e , —C(O)NR f R g , —C(NR e )NR f R g , —OR e , —OC(O)R e , —OC(O)OR e , —OC(O)NR f R g , —OC(═NR e )NR f R g , —OS(O)R e , —OS(O) 2 R e , —OS(O)NR f R g , —OS(O) 2 NR f R g , —NR f R g , —NR e C(O)R h , —NR e C(O)OR f , —NR e C(O)NR f R g , —NR e C(═NR h )NR f R g , —NR e S(O)R h , —NR e S(O) 2 R h , —NR e S(O)NR f R g , —NR e S(O) 2 NR f R g , —P(O)R e R h , —P(O)(OR e )R h , —P(O)(OR e )(OR h ), —SR e , —S(O)R e , —S(O) 2 R e , —SF 5 , —S(O)NR f R g , and —S(O) 2 NR f R g ; wherein each R e , R f , R g , and R h  is independently (i) hydrogen; (ii) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclyl-C 1-6  alkyl; or (iii) R f  and R g  together with the N atom to which they are attached form heterocyclyl. 
 
       
     
     
         57 . A method for the treatment, prevention, or amelioration of one or more symptoms of a basophil-related disorder, disease, or condition in a subject, which comprises administering to the subject acetic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, formic acid, hydrobromic acid, hydrochloric acid, methanesulfonic acid, oxalic acid, phosphoric acid, sulfuric acid, tartaric acid, p-toluenesulfonic acid, or trifluoroacetic acid salt of a compound of Formula IA: 
       
         
           
           
               
               
           
         
         or a stereoisomer, enantiomer, mixture of enantiomers, mixture of diastereomers, or isotopic variant thereof; or a pharmaceutically acceptable solvate, hydrate, or prodrug thereof; wherein:
 R 1  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 2  is C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 3  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; 
 R 4  is cyano, aminocarbonyl, —C(O)N═CR 4a R 4b , or —C(O)NR 4a R 4b ; wherein:
 R 4a  is C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; and 
 R 4b  is independently hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )R 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; 
 
 R 5  is —N(R 5e )CR 5a R 5c R 5d ; wherein:
 R 5a  is C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 5c  and R 5d  are each independently hydrogen, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; and 
 R 5e  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; and 
 
 each R 1a , R 1b , R 1c , and R 1d  is independently hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; or R 1a  and R 1c  together with the C and N atoms to which they are attached form heterocyclyl; or R 1b  and R 1c  together with the N atom to which they are attached form heterocyclyl; 
 wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substituted with one or more substituents Q, where each Q is independently selected from (a) oxo, cyano, halo, nitro, and pentafluorosulfanyl; (b) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclyl-C 1-6  alkyl, each of which is further optionally substituted with one or more substituents Q a ; and (c) —B(R a )OR d , —B(OR a )OR d , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR 1a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , and —S(O) 2 NR b R c , wherein each R a , R b , R c , and R d  is independently (i) hydrogen; (ii) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclyl-C 1-6  alkyl, each optionally substituted with one or more substituents Q a ; or (iii) R b  and R c  together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q a ; 
 wherein each Q a  is independently selected from the group consisting of (a) oxo, cyano, halo, nitro, and pentafluorosulfanyl; (b) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclyl-C 1-6  alkyl; and (c) —B(R e )OR g , —B(OR e )OR g , —C(O)R e , —C(O)OR e , —C(O)NR f R g , —C(NR e )NR f R g , —OR e , —OC(O)R e , —OC(O)OR e , —OC(O)NR f R g , —OC(═NR e )NR f R g , —OS(O)R e , —OS(O) 2 R e , —OS(O)NR f R g , —OS(O) 2 NR f R g , —NR f R g , —NR e C(O)R h , —NR e C(O)OR f , —NR e C(O)NR f R g , —NR e C(═NR h )NR f R g , —NR e S(O)R h , —NR e S(O) 2 R h , —NR e S(O)NR f R g , —NR e S(O) 2 NR f R g , —P(O)R e R h , —P(O)(OR e )R h , —P(O)(OR e )(OR h ), —SR e , —S(O)R e , —S(O) 2 R e , —SF 5 , —S(O)NR f R g , and —S(O) 2 NR f R g ; wherein each R e , R f , R g , and R h  is independently (i) hydrogen; (ii) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclyl-C 1-6  alkyl; or (iii) R f  and R g  together with the N atom to which they are attached form heterocyclyl. 
 
       
     
     
         58 . A method for the treatment, prevention, or amelioration of one or more symptoms of a mast cell-related disorder, disease, or condition in a subject, which comprises administering to the subject acetic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, formic acid, hydrobromic acid, hydrochloric acid, methanesulfonic acid, oxalic acid, phosphoric acid, sulfuric acid, tartaric acid, p-toluenesulfonic acid, or trifluoroacetic acid salt of a compound of Formula IA: 
       
         
           
           
               
               
           
         
         or a stereoisomer, enantiomer, mixture of enantiomers, mixture of diastereomers, or isotopic variant thereof; or a pharmaceutically acceptable solvate, hydrate, or prodrug thereof; wherein:
 R 1  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 2  is C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 3  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; 
 R 4  is cyano, aminocarbonyl, —C(O)N═CR 4a R 4b , or —C(O)NR 4a R 4b ; wherein:
 R 4a  is C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; and 
 R 4b  is independently hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; 
 
 R 5  is —N(R 5e )CR 5a R 5c R 5d ; wherein:
 R 5a  is C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 5c  and R 5d  are each independently hydrogen, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; and 
 R 5e  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; and 
 
 each R 1a , R 1b , R 1c , and R 1d  is independently hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; or R 1a  and R 1c  together with the C and N atoms to which they are attached form heterocyclyl; or R 1b  and R 1c  together with the N atom to which they are attached form heterocyclyl; 
 wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substituted with one or more substituents Q, where each Q is independently selected from (a) oxo, cyano, halo, nitro, and pentafluorosulfanyl; (b) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclyl-C 1-6  alkyl, each of which is further optionally substituted with one or more substituents Q a ; and (c) —B(R a )OR d , —B(OR a )OR d , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR 1a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , and —S(O) 2 NR b R c , wherein each R a , R b , R c , and R d  is independently (i) hydrogen; (ii) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclyl-C 1-6  alkyl, each optionally substituted with one or more substituents Q a ; or (iii) R b  and R c  together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q a ; 
 wherein each Q a  is independently selected from the group consisting of (a) oxo, cyano, halo, nitro, and pentafluorosulfanyl; (b) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclyl-C 1-6  alkyl; and (c) —B(R e )OR g , —B(OR e )OR g , —C(O)R e , —C(O)OR e , —C(O)NR f R g , —C(NR e )NR f R g , —OR e , —OC(O)R e , —OC(O)OR e , —OC(O)NR f R g , —OC(═NR e )NR f R g , —OS(O)R e , —OS(O) 2 R e , —OS(O)NR f R g , —OS(O) 2 NR f R g , —NR f R g , —NR e C(O)R h , —NR e C(O)OR f , —NR e C(O)NR f R g , —NR e C(═NR h )NR f R g , —NR e S(O)R h , —NR e S(O) 2 R h , —NR e S(O)NR f R g , —NR e S(O) 2 NR f R g , —P(O)R e R h , —P(O)(OR e )R h , —P(O)(OR e )(OR h ), —SR e , —S(O)R e , —S(O) 2 R e , —SF 5 , —S(O)NR f R g , and —S(O) 2 NR f R g ; wherein each R e , R f , R g , and R h  is independently (i) hydrogen; (ii) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclyl-C 1-6  alkyl; or (iii) R f  and R g  together with the N atom to which they are attached form heterocyclyl. 
 
       
     
     
         59 . A method for the treatment, prevention, or amelioration of one or more symptoms of an inflammatory disease in a subject, which comprises administering to the subject acetic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, formic acid, hydrobromic acid, hydrochloric acid, methanesulfonic acid, oxalic acid, phosphoric acid, sulfuric acid, tartaric acid, p-toluenesulfonic acid, or trifluoroacetic acid salt of a compound of Formula IA: 
       
         
           
           
               
               
           
         
         or a stereoisomer, enantiomer, mixture of enantiomers, mixture of diastereomers, or isotopic variant thereof; or a pharmaceutically acceptable solvate, hydrate, or prodrug thereof; wherein:
 R 1  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 2  is C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 3  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; 
 R 4  is cyano, aminocarbonyl, —C(O)N═CR 4a R 4b , or —C(O)NR 4a R 4b ; wherein:
 R 4a  is C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; and 
 R 4b  is independently hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; 
 
 R 5  is —N(R 5e )CR 5a R 5c R 5d ; wherein:
 R 5a  is C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 5c  and R 5d  are each independently hydrogen, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; and 
 R 5e  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; and 
 
 each R 1a , R 1b , R 1c , and R 1d  is independently hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; or R 1a  and R 1c  together with the C and N atoms to which they are attached form heterocyclyl; or R 1b  and R 1c  together with the N atom to which they are attached form heterocyclyl; 
 wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substituted with one or more substituents Q, where each Q is independently selected from (a) oxo, cyano, halo, nitro, and pentafluorosulfanyl; (b) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclyl-C 1-6  alkyl, each of which is further optionally substituted with one or more substituents Q a ; and (c) —B(R a )OR d , —B(OR a )OR d , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR 1a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , and —S(O) 2 NR b R c , wherein each R a , R b , R c , and R d  is independently (i) hydrogen; (ii) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclyl-C 1-6  alkyl, each optionally substituted with one or more substituents Q a ; or (iii) R b  and R c  together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q a ; 
 wherein each Q a  is independently selected from the group consisting of (a) oxo, cyano, halo, nitro, and pentafluorosulfanyl; (b) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclyl-C 1-6  alkyl; and (c) —B(R e )OR g , —B(OR e )OR g , —C(O)R e , —C(O)OR e , —C(O)NR f R g , —C(NR e )NR f R g , —OR e , —OC(O)R e , —OC(O)OR e , —OC(O)NR f R g , —OC(═NR e )NR f R g , —OS(O)R e , —OS(O) 2 R e , —OS(O)NR f R g , —OS(O) 2 NR f R g , —NR f R g , —NR e C(O)R h , —NR e C(O)OR f , —NR e C(O)NR f R g , —NR e C(═NR h )NR f R g , —NR e S(O)R h , —NR e S(O) 2 R h , —NR e S(O)NR f R g , —NR e S(O) 2 NR f R g , —P(O)R e R h , —P(O)(OR e )R h , —P(O)(OR e )(OR h ), —SR e , —S(O)R e , —S(O) 2 R e , —SF 5 , —S(O)NR f R g , and —S(O) 2 NR f R g ; wherein each R e , R f , R g , and R h  is independently (i) hydrogen; (ii) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclyl-C 1-6  alkyl; or (iii) R f  and R g  together with the N atom to which they are attached form heterocyclyl. 
 
       
     
     
         60 . The method of  claim 1 , wherein the disorder, disease, or condition is selected from the group consisting of asthma, allergic asthma, exercise induced asthma, allergic rhinitis, perennial allergic rhinitis, seasonal allergic rhinitis, atopic dermatitis, contact hypersensitivity, contact dermatitis, conjunctivitis, allergic conjunctivitis, eosinophilic bronchitis, food allergies, eosinophilic gastroenteritis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, mastocytosis, hyper IgE syndrome, systemic lupus erythematous, psoriasis, acne, multiple sclerosis, allograft rejection, reperfusion injury, chronic obstructive pulmonary disease, Churg-Strauss syndrome, sinusitis, basophilic leukemia, chronic urticaria, basophilic leukocytosis, eczema, arthritis, rheumatoid arthritis, psoriatic arthritis, fibrosis, osteoarthritis, and cardiovascular disorders. 
     
     
         61 . The method of  claim 1 , wherein the disorder, disease, or condition is asthma, exercise induced asthma, allergic rhinitis, atopic dermatitis, chronic obstructive plumonary disease, allergic conjunctivitis, or fibrosis. 
     
     
         62 . The method of  claim 1 , wherein the disorder, disease, or condition is fibrosis. 
     
     
         63 . The method of  claim 1 , wherein the salt is administered in combination with a second therapeutic agent. 
     
     
         64 . A method for modulating RC kinase activity, comprising contacting a RC kinase with acetic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, formic acid, hydrobromic acid, hydrochloric acid, methanesulfonic acid, oxalic acid, phosphoric acid, sulfuric acid, tartaric acid, p-toluenesulfonic acid, or trifluoroacetic acid salt of a compound of Formula IA: 
       
         
           
           
               
               
           
         
         or a stereoisomer, enantiomer, mixture of enantiomers, mixture of diastereomers, or isotopic variant thereof; or a pharmaceutically acceptable solvate, hydrate, or prodrug thereof; wherein:
 R 1  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 2  is C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 3  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c , 
 R 4  is cyano, aminocarbonyl, —C(O)N═CR 4a R 4b , or —C(O)NR 4a R 4b ; wherein:
 R 4a  is C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; and 
 R 4b  is independently hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c , 
 
 R 5  is —N(R 5e )CR 5a R 5c R 5d ; wherein:
 R 5a  is C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; 
 R 5c  and R 5d  are each independently hydrogen, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; and 
 R 5e  is hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, heterocyclyl, —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —S(O)R 1a , —S(O) 2 R 1a , —S(O)NR 1b R 1c , or —S(O) 2 NR 1b R 1c ; and 
 
 each R 1a , R 1b , R 1c , and R 1d  is independently hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, heteroaryl, or heterocyclyl; or R 1a  and R 1c  together with the C and N atoms to which they are attached form heterocyclyl; or R 1b  and R 1c  together with the N atom to which they are attached form heterocyclyl; 
 wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substituted with one or more substituents Q, where each Q is independently selected from (a) oxo, cyano, halo, nitro, and pentafluorosulfanyl; (b) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclyl-C 1-6  alkyl, each of which is further optionally substituted with one or more substituents Q a ; and (c) —B(R a )OR d , —B(OR a )OR d , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR 1a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R e , and —S(O) 2 NR b R c , wherein each R a , R b , R c , and R d  is independently (i) hydrogen; (ii) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclyl-C 1-6  alkyl, each optionally substituted with one or more substituents Q a ; or (iii) R b  and R c  together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q a ; 
 wherein each Q a  is independently selected from the group consisting of (a) oxo, cyano, halo, nitro, and pentafluorosulfanyl; (b) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclyl-C 1-6  alkyl; and (c) —B(R e )OR g , —B(OR e )OR g , —C(O)R e , —C(O)OR e , —C(O)NR f R g , —C(NR e )NR f R g , —OR e , —OC(O)R e , —OC(O)OR e , —OC(O)NR f R g , —OC(═NR e )NR f R g , —OS(O)R e , —OS(O) 2 R e , —OS(O)NR f R g , —OS(O) 2 NR f R g , —NR f R g , —NR e C(O)R h , —NR e C(O)OR f , —NR e C(O)NR f R g , —NR e C(═NR h )NR f R g , —NR e S(O)R h , —NR e S(O) 2 R h , —NR e S(O)NR f R g , —NR e S(O) 2 NR f R g , —P(O)R e R h , —P(O)(OR e )R h , —P(O)(OR e )(OR h ), —SR e , —S(O)R e , —S(O) 2 R e , —SF 5 , —S(O)NR f R g , and —S(O) 2 NR f R g ; wherein each R e , R f , R g , and R h  is independently (i) hydrogen; (ii) C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, C 6-14  aryl, C 7-15  aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclyl-C 1-6  alkyl; or (iii) R f  and R g  together with the N atom to which they are attached form heterocyclyl.