3,5-diaminopyrazole kinase inhibitors

A compound of Formula IA:

• or a stereoisomer, enantiomer, mixture of enantiomers, mixture of diastereomers, or isotopic variant thereof;
• or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof;
• wherein:
• R1 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, heteroaryl, or heterocyclyl;
• R2 is C3-10 cycloalkyl, C6-14 aryl, heteroaryl, or heterocyclyl;
• R3 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, heteroaryl, heterocyclyl, —C(O)R1a, —C(O)OR1a, —C(O)NR1bR1c, —C(NR1a)NR1bR1c, —S(O)R1a, —S(O)2R1a, —S(O)NR1bR1c, or —S(O)2NR1bR1c;
• R4 is cyano, aminocarbonyl, —C(O)N═CR4aR4b, or —C(O)NR4aR4b;
• wherein:
• R4a is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, heteroaryl, or heterocyclyl;
• and
• R4b is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, heteroaryl, heterocyclyl, —C(O)R1a, —C(O)OR1a, —C(O)NR1bR1c, —C(NR1a)NR1bR1c, —S(O)R1a, —S(O)2R1a, —S(O)NR1bR1c, or —S(O)2NR1bR1c;
• R5 is —N═CR5aR5;
• wherein:
• R5a is C3-10 cycloalkyl, C6-14 aryl, heteroaryl, or heterocyclyl;
• R5b is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, heteroaryl, or heterocyclyl;
• each R1a, R1b, R1c, and R1d is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, heteroaryl, or heterocyclyl;
• or R1a and R1c together with the C and N atoms to which they are attached form heterocyclyl;
• or R1b and R1c 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) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclyl-C1-6 alkyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;
• and (c) —B(Ra)ORd, —B(ORa)ORd, —C(O)Ra, —C(O)ORa, —C(O)NRbRc, —C(NRa)NRbRc, —ORa, —OC(O)Ra, —OC(O)ORa, —OC(O)NRbRc, —OC(═NRa)NRbRc, —OS(O)Ra, —OS(O)2Ra, —OS(O)NRbRc, —OS(O)2NRbRc, —NRbRc, —NRaC(O)Rd, —NRaC(O)ORd, —NRaC(O)NRbRc, —NRaC(═NRd)NRbRc, —NRaS(O)Rd, —NRaS(O)2Rd, —NRaS(O)NRbRc, —NRaS(O)2NRbRc, —P(O)RaRd, —P(O)(ORa)Rd, —P(O)(ORa)(ORd), —SRa, —S(O)Ra, —S(O)2Ra, —S(O)NRbRc, and —S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rd is independently (i) hydrogen;
• (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclyl-C1-6 alkyl, each optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;
• or (iii) Rb and Rc together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;
• wherein each Qa is independently selected from the group consisting of (a) oxo, cyano, halo, nitro, and pentafluorosulfanyl;
• (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclyl-C1-6 alkyl;
• and (c) —B(Re)ORg, —B(ORe)ORg, —C(O)Re, —C(O)ORe, —C(O)NRfRg, —C(NRe)NRfRg, —ORe, —OC(O)Re, —OC(O)ORe, —OC(O)NRfRg, —OC(═NRe)NRfRg, —OS(O)Re, —OS(O)2Re, —OS(O)NRfRg, —OS(O)2NRfRg, —NRfRg, —NReC(O)Rh, —NReC(O)ORf, —NReC(O)NRfRg, —NReC(═NRh)NRfRg, —NReS(O)Rb, —NReS(O)2Rh, —NReS(O)NRfRg, —NReS(O)2NRfRg, —P(O)ReRh, —P(O)(ORe)Rh, —P(O)(ORe)(ORh), —SRe, —S(O)Re, —S(O)2Re, —SF5, —S(O)NRfRg, and —S(O)2NRfRg;
• wherein each Re, Rf, Rg, and Rh is independently (i) hydrogen;
• (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclyl-C1-6 alkyl;
• or (iii) Rf and Rg together with the N atom to which they are attached form heterocyclyl.