Glp-1r agonists and uses thereof

A compound of formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• is a double bond or a single bond;
• X1, X2, X5 and X6 are independently selected from N and C;
• X3 is selected from O, S, N, NR7.3 and CR7.3,
• X4 is absent or selected from N, C(O) and CR7.4;
• Y1 is selected from N and CR8.1;
• Y2 is selected from N and CR8.2;
• Y3 is selected from N and CR8.3;
• Z1 is selected from N and C(O);
• Z2 is selected from N and C;
• W is selected from
• which are each unsubstituted or substituted with at least one substituent, independently selected from RX;
• L is selected from —CRC0RD0(CRC0RD0)u—, —(CRC0RD0)uO(CRC0RD0)t—, —(CRC0RD0)tNRA0(CRC0RD0)t— and —(CRC0RD0)uS(O)r(CRC0RD0)t—;
• Q1, Q2 and Q3 is selected from C3-10 cycloalkyl, heterocyclyl, aryl and heteroaryl;
• each R1, at each occurrence, 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, NO2, —NRA1RB1, —ORA1, —C(O)RA1, —C(═NRE1)RA1, —C(═N—ORB1)RA1, —C(O)ORA1, —OC(O)RA1, —C(O)NRA1RB1, —C(O)NRA1S(O)rRA1, —C(O)NRA1S(O)2ORA1, —C(O)NRA1S(O)rNRA1RB1, —C(O)NRA1S(O)(═NRE1)RB1, —C(O)NRA1S(O)(═NRE1) NRA1RB1, —NRA1C(O)RB1, —C(═NRE1) NRA1RB1, —NRA1C(═NRE1)RB1, —OC(O)NRA1RB1, —NRA1C(O)ORB1, —NRA1C(O)NRA1RB1, —NRA1C(S)NRA1RB1, —NRA1C(═NRE1) NRA1RB1, —S(O)rRA1, —S(O)(═NRE1)RB1, —N═S(O)RA1RB1, —S(O)2ORA1, —OS(O)2RA1, —NRA1S(O)rRB1, —NRA1S(O)(═NRE1)RB1, —S(O)rNRA1RB1, —S(O)(═NRE1) NRA1RB1, —NRA1S(O)2NRA1RB1, —NRA1S(O)(═NRE1) NRA1RB1, —P(O)RA1RB1 and —P(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 RX1;
• each R2, at each occurrence, 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, NO2, —NRA2RB2, —ORA2, —C(O)RA2, —C(═NRE2)RA2, —C(═N—ORB2)RA2, —C(O)ORA2, —OC(O)RA2, —C(O)NRA2RB2, —C(O)NRA2S(O)(═NRE2)RB2, —C(O)NRA2S(O)(═NRE2) NRA2RB2, —NRA2C(O)RB2, —C(═NRE2) NRA2RB2, —NRA2C(═NRE2)RB2, —OC(O)NRA2RB2, —NRA2C(O)ORB2, —NRA2C(O)NRA2RB2, —NRA2C(S)NRA2RB2, —NRA2C(═NRE2) NRA2RB2, —S(O)(═NRE2)RB2, —N═S(O)RA2RB2, —NRA2S(O)(═NRE2)RB2, —S(O)(═NRE2) NRA2RB2 and —NRA2S(O)(═NRE2) NRA2RB2, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from RX2;
• each R3, at each occurrence, 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, NO2, —NRA3RB3, —ORA3, —C(O)RA3, —C(═NRE3)RA3, —C(═N—ORB3)RA3, —C(O)ORA3, —OC(O)RA3, —C(O)NRA3RB3, —C(O)NRA3S(O)rRA3, —C(O)NRA3S(O)2ORA3, —C(O)NRA3S(O)tNRA3RB3, —C(O)NRA3S(O)(═NRE3)RB3, —C(O)NRA3S(O)(═NRE3)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, —NRA3 S(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;
• R4 is selected from —C(O)OH, —C(O)NHS(O)rRA4, —(CRc1Rd1) NHS(O)rRA4, heterocyclyl and heteroaryl;
• R5 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, CN, NO2, —NRA5RB5, —ORA5 and —C(O)RA5, wherein alkyl, alkenyl, alkynyl, cycloalkyl and heterocyclyl are each unsubstituted or substituted with at least one substituent, independently selected from RX5;
• each R6, at each occurrence, 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, CN, NO2, —NRA6RB6, —ORA6 and —C(O)RA6, wherein alkyl, alkenyl, alkynyl, cycloalkyl and heterocyclyl are each unsubstituted or substituted with at least one substituent, independently selected from RX6;
• or “R5 and R6” or “two of R6” 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, wherein cycloalkyl and heterocyclic ring are each unsubstituted or substituted with at least one substituent, independently selected from RX6,
• R7.3 and R7.4 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, heteroaryl-C1-4 alkyl, CN, NO2, —NRA7RB7, —ORA7, —C(O)RA7, —C(═NRE7)RA7, —C(═N—ORB7)RA7, —C(O)ORA7, —OC(O)RA7, —C(O)NRA7RB7, —C(O)NRA7S(O)rRA7, —C(O)NRA7S(O)2ORA7, —C(O)NRA7S(O)rNRA7RB7, —C(O)NRA7S(O)(═NRE7)RB7, —C(O)NRA7S(O)(═NRE7) 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, —NR47S(O)(═NRE7)RB7, —S(O)rNRA7RB7, —S(O)(═NRE7) NR 47RB7, —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;
• R8.1, R8.2 and R8.3 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, heteroaryl-C1-4 alkyl, CN, NO2, —NRA8RB8, —ORA8, —C(O)RA8, —C(═NRE8)RA8, —C(═N—ORB8)RA8, —C(O)ORA8, —OC(O)RA8, —C(O)NRA8RB8, —C(O)NRA8S(O)rRA8, —C(O)NRA8S(O)2ORA8, —C(O)NRA8S(O)rNRA8RB8, —C(O)NRA8S(O)(═NRE8)RB8, —C(O)NRA8S(O)(═NRE8) NRA8RB8, —NRA8C(O)RB8, —C(═NRE8) NRA8RB8, —NRA8C(═NRE8)RB8, —OC(O)NRA8RB8, —NRA8C(O)ORB8, —NRA8C(O)NRA8RB8, —NRA8C(S)NRA8RB8, —NRA8C(═NRE8) NRA8RB8, —S(O)rRA8, —S(O)(═NRE8)RB8, —N═S(O)RA8RB8, —S(O)2ORA8, —OS(O)2RA8, —NRA8S(O)rRB8, —NRA8S(O)(═NRE8)RB8, —S(O)rNRA8RB8, —S(O)(═NRE8) NRA8RB8, —NRA8S(O)2NRA8RB8, —NRA8S(O) (—NRE8) NRA8RB8, —P(O)RA8RB8 and —P(O)(ORA8)(ORB8), wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, independently selected from RX8;
• RA0 is selected from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, C1-10 alkoxy, 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 RX0;
• each RA1 and RBI 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, 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 RX1;
• or each “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 RX1 groups;
• each RA2 and 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, 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 RX2;
• or each “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, 2 or 3 RX2 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, C1-10 alkoxy, 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 each “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;
• RA4 is selected from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4 alkyl, C1-10 alkoxy, 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;
• each RA5 and RB5 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, 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,
• or each “RA5 and RB5” 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 RX5 groups;
• each RA6 and RB6 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, 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,
• or each “RA6 and RB6” 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 RX6 groups;
• 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, C1-10 alkoxy, 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 RA8 and RB8 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, 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 RX8,
• or each “RA8 and RB8” 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 RX8 groups;
• each RC0 and RD0 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, 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 RX0;
• or RC0 and RD0 together with the carbon 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, wherein cycloalkyl and heterocyclic ring are each unsubstituted or substituted with at least one substituent, independently selected from RX0:
• each RE1, RE2, RE3, RE7 and RE8 are independently selected from hydrogen, C1-10 alkyl, CN, NO2, —ORa1, —SRa1, —S(O)rRal, —C(O)Ra1, —C(O)ORa1, —C(O)NRa1Rb1 and —S(O)rNRa1Rb1, wherein alkyl is unsubstituted or substituted with at least one substituent, independently selected from RX;
• each RX, RX0, RX1, RX2, RX3, RX4, RX5, RX6, RX7 and RX8 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, —(CRe1Rd1)C(O)ORb1, —(CRc1Rd1)tC(O)Rb1, —(CRc1Rd1)tC(O)NRa1Rb1, —(CRc1Rd1)tNRa1C(O)Rb1, —(CRc1Rd1)tC(═NRe1) NRa1Rb1, —(CRc1Rd1)tNRa1C(═NRe1)Rb1, —(CRc1Rd1)tC(O)NRa1Rb1, —(CRc1Rd1)tNRa1C(O)ORb1, —(CRc1Rd1)tNRa1C(O)NRa1Rb1, —(CRc1Rd1) NRa1C(S)NRa1Rb1, —(CRc1Rd1)tNRa1C(═NRe1) NRa1Rb1, —(CRc1Rd1)S(O)rRb1, —(CRc1Rd1)tS(O)(═NRe1)Rb1, —(CRc1Rd1)tN═S(O)Ra1Rb1, —(CRc1Rd1)tS(O)2ORb1, —(CRc1Rd1)tS(O)2Rb1, —(CRc1Rd1)tNRa1S(O)rRb1, —(CRc1Rd1)tNRa1S(O)(═NRe1)Rb1, —(CRc1Rd1)tS(O)rNRa1Rb1, —(CRc1Rd1)tS(O)(═NRe1) NRa1Rb1, —(CRc1Rd1)tNRa1S(O)2NRa1Rb1, —(CRc1Rd1)tNRa1S(O)(═NRe1) NRa1Rb1, —(CRc1Rd1)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 Re1 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 Re1 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)tC(O)Rb2, —(CRc2Rd2)tC(O)NRa2Rb2, —(CRc2Rd2), NRa2C(O)Rb2, (CRc2Rd2)tC(═NRe2)NRa2Rb2, —(CRc2Rd2), NRa2C(═NRe2)Rb2, —(CRc2Rd2), OC(O)NRa2Rb2, —(CRc2Rd2)tNRa2C(O)ORb2, —(CRc2Rd2)tNRa2C(O)NRa2Rb2, —(CRc2Rd2), NRa2C(S)NRb2Rb2, —(CRc2Rd2)tNRa2C(═NRe2)NRa2Rb2, —(CRc2Rd2)tS(O)rRb2, —(CRc2Rd2);
• S(O)(═NRe2)Rb2, —(CRc2Rd2)tN═S(O)Ra2Rb2, —(CRc2Rd2)tS(O)2ORb2, —(CRc2Rd2), OS(O)2Rb2, —(CRc2Rd2)tNRa2S(O), Rb2, —(CRc2Rd2)tNRa2S(O)(═NRe2)Rb2, —(CRc2Rd2)S(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 Re2 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, n, p and q are independently selected from 0, 1, 2, 3 and 4;
• each r is independently selected from 0, 1 and 2;
• each tis independently selected from 0, 1, 2, 3 and 4;
• each u is independently selected from 0, 1, 2, 3 and 4,
• provided that when Z1 is N, X2 is C, X3 is CR7.3 or N, X4 is absent, R5 and R6 or any two of R6 do not form any ring, W is
• and L is selected from —CRC0RD0 (CRC0RD0)u—, then at least one of RC0 and RD0 is substituted with RX0, and RX0 is selected from CN, C2-10 alkenyl and C2-10 alkynyl.