Compounds useful as kinase inhibitors

A compound of formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• is a single bond or a double bond to maintain ring A and ring B being aromatic;
• A1 is selected from C and N;
• A2 is selected from CRX, C(O) and N;
• A3 is selected from CR6 and NR6;
• A4 selected from CR7, C(O), N and NRXR5;
• A5 is selected from CRX, NRX or absent;
• A6 is selected from N and O;
• B1 is selected from C and N;
• B2 is selected from C and N;
• when A4 and A6 are N, B2 is C, then A2 is not N;
• when A5 is absent, R5 and R6 together with the atoms to which they are attached are not form a ring, then A2 and A3 are not N at the same time;
• X is selected from CRX and N;
• Y is selected from CRX and N;
• Z is selected from aryl, heteroaryl and heterocyclyl, wherein aryl, heteroaryl and heterocyclyl are each unsubstituted or substituted with at least one substituent, independently selected from Rx;
• R1 is selected from hydrogen, C1-10 alkyl and C3-10 cycloalkyl, wherein alkyl and cycloalkyl are each unsubstituted or substituted with at least one substituent, independently selected from RX1;
• R2 is selected from hydrogen, C1-10 alkyl and C3-10 cycloalkyl, wherein alkyl and cycloalkyl are each unsubstituted or substituted with at least one substituent, independently selected from RX2;
• or R1 and R2 together with the atom(s) to which they are attached form a C3-10 cycloalkyl or heterocyclic ring of 4 to 12 members containing 1, 2 or 3 heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus, and optionally substituted with 1, 2 or 3 RX1 groups;
• each R3 is independently selected from halogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl, heteroaryl-C1-4 alkyl, CN, NO2, —NRA3RB3, —ORA3, —C(O)RA3, —C(═NRE3)RA3, —C(═N—ORB3)RA3, —C(O)ORA3, —OC(O)RA3, —C(O)NRA3RB3, —NRA3C(O)RB3, —C(═NRE3)NRA3RB3, —NRA3C(═NRE3)RB3, —OC(O)NRA3RB3, —NRA3C(O)ORB3, —NRA3C(O)NRA3RB3, —NRA3C(S)NRA3RB3, —NRA3C(═NRE3)NRA3RB3, —S(O)rRA3, —S(O)(═NRE3)RB3, —N═S(O)RA3RB3, —S(O)2ORA3, —OS(O)2RA3, —NRA3S(O)rRB3, —NRA3S(O)(═NRE3)RB3, —S(O)rNRA3RB3, —S(O)(═NRE3)NRA3RB3, —NRA3S(O)2NRA3RB3, —NRA3S(O)(═NRE3)NRA3RB3, —P(O)RA3RB3 and —P(O)(ORA3)(ORB3), wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from RX3;
• or any two of R3 together with the atoms to which they are attached form a C3-10 cycloalkyl or heterocyclic ring of 4 to 12 members containing 1, 2 or 3 heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus, and optionally substituted with 1, 2 or 3 RX3 groups;
• R5 is selected from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl, heteroaryl-C1-4 alkyl and —C(O)RA5, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from RX5;
• R6 is selected from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl, heteroaryl-C1-4 alkyl and —C(O)RA6, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from RX6;
• or R5 and R6 together with the atoms to which they are attached form a C3-10 cycloalkyl or heterocyclic ring of 4 to 12 members containing 1, 2 or 3 heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus, and optionally substituted with 1, 2, 3 or 4 R4 groups;
• each R4 is independently selected from hydrogen, halogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl, heteroaryl-C1-4 alkyl, CN, —NRA4RB4, —ORA4, —C(O)RA4, —C(O)ORA4, —OC(O)RA4, —C(O)NRA4RB4, —NRA4C(O)RB4, and —S(O)rRA4, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from RX4;
• or any two of R4 together with the atom(s) to which they are attached form a C3-10 cycloalkyl or heterocyclic ring of 4 to 12 members containing 1, 2 or 3 heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus, and optionally substituted with 1, 2 or 3 RX4 groups;
• R7 is selected from hydrogen, halogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl, heteroaryl-C1-4 alkyl, CN, NO2, —NRA7RB7, —ORA7, —C(O)RA1, —C(═NRE7)RA7, —C(═N—ORB7)RA7, —C(O)ORA7, —OC(O)RA7, —C(O)NRA7RB7, —NRA7C(O)RB7, —C(═NRE7)NRA7RB7, —NRA7C(═NRE7)RB7, —OC(O)NRA7RB7, —NRA7C(O)ORB7, —NRA7C(O)NRA7RB7, —NRA7C(S)NRA7RB7, —NRA7C(═NRE7)NRA7RB7, —S(O)rRA7, —S(O)(═NRE7)RB7, —N═S(O)RA7RB7, —S(O)2ORA7, —OS(O)2RA7, —NRA7S(O)rRB7, —NRA7S(O)(═NRE7)RB7, —S(O)rNRA7RB7, —S(O)(═NRE7)NRA7RB7, —NRA7S(O)2NRA7RB7, —NRA7S(O)(═NRE7)NRA7RB7, —P(O)RA7RB7 and —P(O)(ORA7)(ORB7), wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from RX7;
• or R6 and R7 together with the atoms to which they are attached form a C3-10 cycloalkyl or heterocyclic ring of 4 to 12 members containing 1, 2 or 3 heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus, and optionally substituted with 1, 2 or 3 RX6 groups;
• each RA3 and RB3 are independently selected from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl and heteroaryl-C1-4 alkyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from RX3;
• or “RA3 and RB3”, together with the atom(s) to which they are attached form a heterocyclic ring of 4 to 12 members containing 0, 1 or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus and optionally substituted with 1, 2 or 3 RX3 groups;
• each RA4 and RB4 are independently selected from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl, and heteroaryl-C1-4 alkyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from RX4;
• or each “RA4 and RB4”, together with the atom(s) to which they are attached form a heterocyclic ring of 4 to 12 members containing 0, 1 or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus, and optionally substituted with 1, 2 or 3 RX4 groups;
• RA is selected from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl, and heteroaryl-C1-4 alkyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from RX5;
• RA6 is selected from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl, and heteroaryl-C1-4 alkyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from RX6;
• each RA7 and RB7 are independently selected from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl, and heteroaryl-C1-4 alkyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from RX7;
• or each “RA7 and RB7” together with the atom(s) to which they are attached form a heterocyclic ring of 4 to 12 members containing 0, 1 or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus, and optionally substituted with 1, 2 or 3 RX7 groups;
• each RE3 and RE7 are independently selected from hydrogen, C1-10 alkyl, CN, NO2, —ORa1, —SRa1, —S(O)rRa1, —C(O)Ra1, —C(O)ORa1, —C(O)NRa1Rb1 and —S(O)rNRa1Rb1;
• each RX, RX1, RX2, RX3, RX4, RX5, RX6 and RX7 are independently selected from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl, heteroaryl-C1-4 alkyl, halogen, CN, NO2, —(CRc1Rd1)tNRa1Rb1, —(CRc1Rd1)tORb1, —(CRc1Rd1)tC(O)Ra1, —(CRc1Rd1)tC(═NRe1)Ra1, —(CRc1Rd1)tC(═N—ORb1)Ra1, —(CRc1Rd1)tC(O)ORb1, —(CRc1Rd1)tOC(O)Rb1, —(CRc1Rd1)tC(O)NRa1Rb1, —(CRc1Rd1)NRa1C(O)Rb1, —(CRc1Rd1)tC(═NRe1)NRa1Rb1, —(CRc1Rd1)tRa1C(═NRe1)Rb1, —(CRc1Rd1)tOC(O)NRa1Rb1, —(CRc1Rd1)tRa1C(O)ORb1, —(CRc1Rd1)tRa1C(O)NRa1Rb1, —(CRc1Rd1)NRa1C(S)NRa1Rb1, —(CRc1Rd1)NRa1C(═NRe1)NRa1Rb1, —(CRc1Rd1)tS(O)rRb1, —(CRc1Rd1)tS(O)(═NRe1)Rb1, —(CRc1Rd1)tN═S(O)Ra1Rb1, —(CRc1Rd1)tS(O)2ORb1, —(CRc1Rd1)tOS(O)2Rb1, —(CRc1Rd1)tNRa1S(O)rRb1, —(CRc1Rd1)NRa1S(O)(═NRe1)Rb1, —(CRc1Rd1)tS(O)rNRa1Rb1, —(CRc1Rd1)tS(O)(═NRe1)NRa1Rb1, —(CRc1Rd1)tNRa1S(O)2NRa1Rb1, —(CRc1Rd1)tNRa1S(O)(═NRe1)NRa1Rb1, —(CRc1Ra1)tP(O)Ra1Rb1 and —(CRc1Rd1)tP(O)(ORa1)(ORb1), wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from RY;
• each Ra1 and each Rb1 are independently selected from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl and heteroaryl-C1-4 alkyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from RY;
• or Ra1 and Rb1 together with the atom(s) to which they are attached form a heterocyclic ring of 4 to 12 members containing 0, 1 or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus, and optionally substituted with 1, 2 or 3 RY groups;
• each Rc1 and each Rd1 are independently selected from hydrogen, halogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl and heteroaryl-C1-4 alkyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from RY;
• or Rc1 and Rd1 together with the carbon atom(s) to which they are attached form a ring of 3 to 12 members containing 0, 1 or 2 heteroatoms independently selected from oxygen, sulfur and nitrogen, and optionally substituted with 1, 2 or 3 RY groups;
• each Re1 is independently selected from hydrogen, C1-10 alkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, CN, NO2, —ORa2, —SRa2, —S(O)rRa2, —C(O)Ra2, —C(O)ORa2, —S(O)rNRa2Rb2 and —C(O)NRa2Rb2;
• each RY is independently selected from C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl, heteroaryl-C1-4 alkyl, halogen, CN, NO2, —(CRc2Rd2)tNRa2Rb2, —(CRc2Rd2)tORb2, —(CRc2Rd2)tC(O)Ra2, —(CRc2Rd2)tC(═NRe2)Ra2, —(CRc2Rd2)tC(═N—ORb2)Ra2, —(CRc2Rd2)tC(O)ORb2, —(CRc2Rd2)tOC(O)Rb2, —(CRc2Rd2)tC(O)NRa2Rb2, —(CRc2Rd2)NRa2C(O)Rb2, —(CRc2Rd2)tC(═NRe2)NRa2Rb2, —(CRc2Rd2)tNRa2C(═NRe2)Rb2, —(CRc2Rd2)tOC(O)NRa2Rb2, —(CRc2Rd2)tNRa2C(O)ORb2, —(CRc2Rd2)tNRa2C(O)NRa2Rb2, —(CRc2Rd2)tRa2C(S)NRa2Rb2, —(CRc2Rd2)NRa2C(═NRe2)NRa2Rb2, —(CRc2Rd2)tS(O)rRb2, —(CRc2Rd2)tS(O)(═NRe2)Rb2, —(CRc2Rd2)tN═S(O)Ra2Rb2, —(CRc2Rd2)tS(O)2ORb2, —(CRc2Rd2)tOS(O)2Rb2, —(CRc2Rd2)tRa2S(O)rRb2, —(CRc2Rd2)tRa2S(O)(═NRe2)Rb2, —(CRc2Rd2)tS(O)rNRa2Rb2, —(CRc2Rd2)tS(O)(═NRe2)NRa2Rb2, —(CRc2Rd2)tNRa2S(O)2NRa2Rb2, —(CRc2Rd2)tNRa2S(O)(═NRe2)NRa2Rb2, —(CRc2Rd2)tP(O)Ra2Rb2 and —(CRc2Rd2)tP(O)(ORa2)(ORb2), wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from OH, CN, amino, halogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C1-10 alkoxy, C3-10 cycloalkoxy, C1-10 alkylthio, C3-10 cycloalkylthio, C1-10 alkylamino, C3-10 cycloalkylamino and di(C1-10 alkyl)amino;
• each Ra2 and each Rb2 are independently selected from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, C1-10 alkoxy, C3-10 cycloalkoxy, C1-10 alkylthio, C3-10 cycloalkylthio, C1-10 alkylamino, C3-10 cycloalkylamino, di(C1-10 alkyl)amino, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl and heteroaryl-C1-4 alkyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, cycloalkoxy, alkylthio, cycloalkylthio, alkylamino, cycloalkylamino, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from halogen, CN, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, OH, C1-10 alkoxy, C3-10 cycloalkoxy, C1-10 alkylthio, C3-10 cycloalkylthio, amino, C1-10 alkylamino, C3-10 cycloalkylamino and di(C1-10 alkyl)amino;
• or Ra2 and Rb2 together with the atom(s) to which they are attached form a heterocyclic ring of 4 to 12 members containing 0, 1 or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus, and optionally substituted with 1 or 2 substituents, independently selected from halogen, CN, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, OH, C1-10 alkoxy, C3-10 cycloalkoxy, C1-10 alkylthio, C3-10 cycloalkylthio, amino, C1-10 alkylamino, C3-10 cycloalkylamino and di(C1-10 alkyl)amino;
• each Rc2 and each Rd2 are independently selected from hydrogen, halogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, C1-10 alkoxy, C3-10 cycloalkoxy, C1-10 alkylthio, C3-10 cycloalkylthio, C1-10 alkylamino, C3-10 cycloalkylamino, di(C1-10 alkyl)amino, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl and heteroaryl-C1-4 alkyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, cycloalkoxy, alkylthio, cycloalkylthio, alkylamino, cycloalkylamino, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from halogen, CN, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, OH, C1-10 alkoxy, C3-10 cycloalkoxy, C1-10 alkylthio, C3-10 cycloalkylthio, amino, C1-10 alkylamino, C3-10 cycloalkylamino and di(C1-10 alkyl)amino;
• or Rc2 and Rd2 together with the carbon atom(s) to which they are attached form a ring of 3 to 12 members containing 0, 1 or 2 heteroatoms independently selected from oxygen, sulfur and nitrogen, and optionally substituted with 1 or 2 substituents, independently selected from halogen, CN, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, OH, C1-10 alkoxy, C3-10 cycloalkoxy, C1-10 alkylthio, C3-10 cycloalkylthio, amino, C1-10 alkylamino, C3-10 cycloalkylamino and di(C1-10 alkyl)amino;
• each Re2 is independently selected from hydrogen, CN, NO2, C1-10 alkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, C1-10 alkoxy, C3-10 cycloalkoxy, —C(O)C1-4 alkyl, —C(O)C3-10 cycloalkyl, —C(O)OC1-4 alkyl, —C(O)OC3-10 cycloalkyl, —C(O)N(C1-4 alkyl)2, —C(O)N(C3-10 cycloalkyl)2, —S(O)2C1-4 alkyl, —S(O)2C3-10 cycloalkyl, —S(O)2N(C1-4 alkyl)2 and —S(O)2N(C3-10 cycloalkyl)2;
• m is selected from 0, 1, 2, 3 and 4;
• each r is independently selected from 0, 1 and 2;
• each t is independently selected from 0, 1, 2, 3 and 4.