Pyridazinones as PARP7 inhibtors

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• X is Cl, Br, F, CH3, CF3, CF2H, CN, OCH3, ethyl, cyclopropyl, SCH3, or isopropyl;
• A is a group having a formula that is (A-1):
• Y1, Y2, and Y3 are each independently selected from —O—, —S—, —N(RY)—, —C(═O)—, —C(═O)O—, —C(═O)N(RY)—, —S(═O)—, —S(═O)2—, —S(═O)N(RY)—, —S(═O)2N(RY)— or —N(RY)C(═O)N(RY)—, wherein each RY is independently H, C1-4 alkyl, or C1-4 haloalkyl;
• L is C1-3 alkylene, —O—, —S—, —N(RY)—, —C(═O)—, —C(═O)O, C(═O)N(R)—, —S(═O)—, —S(═O)N(RY)—, or —N(R)C(═O)N(RY)—;
• Z is H, CyZ, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, C(═NRe)Rb, C(═NRe)NRcRd, NRcC(═NRe)NRcRd, NRcS(O)Rb, NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, and S(O)2NRcRd;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl of Z are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from CyZ, halo, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, C(═NRe)NRcRd, NRcC(═NRe)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, NRcS(O)Rb, NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, and S(O)2NRcRd;
• CyZ is selected from C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, each optionally substituted by 1, 2, 3, or 4 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRe1)NRc1Rd1, NRc1(═NRe)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1, wherein the alkyl, C2-6 alkenyl, and C2-6 alkynyl are optionally substituted with 1, 2, or 3 substituents independently selected from halo, CN, NO2, ORa, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRe1)NRc1Rd1, NRc1C(═NRe)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)2NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1;
• Ring D is an azetidine ring or piperidine ring optionally substituted with 1, 2, or 3 groups independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRe2)NRc2Rd2, NRc2C(═NRe2)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2 NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, or 3 groups independently selected from halo, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRc2)NRc2Rd2 NRc2C(═Rc2)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2 NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• R1, R2, R3, R4, R5, R6, R7, R9, R10, R11, and R12 are each independently selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-7 cycloalkyl-C1-4 alkyl, 5-10 membered heteroaryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, CN, NO2, ORa, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3 NRc3C(O)Rb3 NRc3C(O)ORa3, NRc3C(O)NRc3Rd3 C(═NRe3)Rb3, C(═NRe3)NRc3Rd3, NRc3C(═NRe3)NRc3Rd3 NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-7 cycloalkyl-C1-4 alkyl, 5-10 membered heteroaryl-C1-4 alkyl, and 4-10 membered heterocycloalkyl-C1-4 alkyl of said R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12 are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(═NRe3)Rb3, C(═NRe3)NRc3Rd3, NRc3C(═NRe3)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• or R1 and an RY group of Y1, together with the atoms to which they are attached and together with the atoms forming Y1 form a 4-10 membered heterocycloalkyl ring, optionally substituted with 1, 2, or 3 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(═NRe3)Rb3, C(═NRe3)NRc3Rd3, NRc3C(═NRe3)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• or R7 and an R group of Y3, together with the atoms to which they are attached and together with the atoms forming Y3 and together with the carbon atoms substituted by R9, R10, R11, and R12, if present, form a 4-10 membered heterocycloalkyl ring, optionally substituted with 1, 2, or 3 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(═NRe3)Rb3, C(═NRe3)NRc3Rd3, NRc3C(═NRe3)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• or R1 and R3 together with the carbon atoms to which they are attached form a C5-10 cycloalkyl ring or a 5-10 membered heterocycloalkyl ring, each optionally substituted with 1, 2, or 3 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3 NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(═NRe3)Rb3, C(═NRe3)NRc3Rd3, NRc3C(═NRe3)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• or R3 and R5 together with the carbon atoms to which they are attached form a C5-10 cycloalkyl ring or a 5-10 membered heterocycloalkyl ring, each optionally substituted with 1, 2, or 3 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(═NRe3)Rb3, C(═NRe3)NRc3Rd3, NRc3C(═NRe3)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• or R7 and R9 together with the carbon atoms to which they are attached form a C5-10 cycloalkyl ring or a 5-10 membered heterocycloalkyl ring, each optionally substituted with 1, 2, or 3 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(═NRe3)Rb3, C(═NRe3)NRc3Rd3, NRc3C(═NRe3)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• or R9 and R11 together with the carbon atoms to which they are attached form a C5-10 cycloalkyl ring or a 5-10 membered heterocycloalkyl ring, each optionally substituted with 1, 2, or 3 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(═NRe3)Rb3, C(═NRe3)NRc3Rd3 NRc3C(═NRe3)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• or R5 and R7 together with the carbon atoms to which they are attached and together with Y2 form a 5-10 membered heterocycloalkyl ring optionally substituted with 1, 2, or 3 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3 C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3 NRc3Rd3 NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(═NRe3)Rb3, C(═NRe3)NRc3Rd3, NRc3C(═NRe3)NRc3Rd3 NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• or R1 and R3 together form a double bond between the carbon atoms to which they are attached;
• or R3 and R5 together form a double bond between the carbon atoms to which they are attached;
• or R7 and R9 together form a double bond between the carbon atoms to which they are attached;
• or R9 and R11 together form a double bond between the carbon atoms to which they are attached;
• or R9, R10, R11, and R12 together form a triple bond between the carbon atoms to which they are attached;
• each Ra, Rb, Rc, Rd, Ra1, Rb1, Rc1, Rd1, Ra2, Rb2, Rc2, Rd2, Ra3, Rb3, Rc3, and Rd3 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-7 cycloalkyl-C1-4 alkyl, 5-10 membered heteroaryl-C1-4 alkyl, and 4-10 membered heterocycloalkyl-C1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4alkyl, C3-7 cycloalkyl-C1-4 alkyl, 5-10 membered heteroaryl-C1-4 alkyl, and 4-10 membered heterocycloalkyl-C1-4 alkyl of said Ra, Rb, Rc, Rd, Ra1, Rb1, Rc1, Rd1, Ra2, Rb2, Rc2, Rd2, Ra3, Rb3, Rc3, and Rd3 is optionally substituted with 1, 2, or 3 substituents independently selected from halo, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, OC(O)Rb7, OC(O)NRc7Rd7, NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)NRc7Rd7, NRc7C(O)ORa7, C(═NRe7)NRc7Rd7, NRc7C(═NRe7)NRc3Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, NRc7S(O)2Rb7, NRc7S(O)2NRc7Rd7, and S(O)2NRc7Rd7;
• or Rc and Rd together with the N atom to which they are attached form a 4-7 membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from CN, halo, C1-4 alkyl, C1-4 haloalkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, ORa7, SRa7, C(O)Rb7, C(O)NRe7Rd7, C(O)ORa7, OC(O)Rb7, OC(O)NRe7Rd7, NRe7Rd7, NRc7C(O)Rb7, NRc7C(O)NRc7Rc7, NRc7C(O)ORa7, C(═NRe7)NRc7Rd7, NR7C(═NRe7)NRc3Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, NRc7S(O)2Rb7, NRc7S(O)2NRc7Rd7 and S(O)2NRe7Rd7;
• or Rc1 and Rd2 together with the N atom to which they are attached form a 4-7 membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from CN, halo, C1-4 alkyl, C1-4 haloalkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, OC(O)Rb7, OC(O)NRc7Rd7, NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)NRc7Rd7, NRc7C(O)ORa7, C(═NRe7)NRc7Rd7, NR7C(═NRe7)NRc3Rd7 S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, NRc7S(O)2Rb7 NRc7S(O)2NRc7Rd7 and S(O)2NRe7Rd7;
• or Rc2 and Rd2 together with the N atom to which they are attached form a 4-7 membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from CN, halo, C1-4 alkyl, C1-4 haloalkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, OC(O)Rb7, OC(O)NRc7Rd7, NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)NRc7Rd7, NRc7C(O)ORa7, C(═NRe7)NRc7Rd7, NRc7C(═NRe7)NRc3Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, NRc7S(O)2Rb7, NRc7S(O)2NRe7Rd7, and S(O)2NRe7Rd7;
• or Re3 and Rd3 together with the N atom to which they are attached form a 4-7 membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from CN, halo, C1-4 alkyl, C1-4 haloalkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, OC(O)Rb7, OC(O)NRc7Rd7, NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)NRc7Rd7, NRc7C(O)ORa7, C(═NRe7)NRc7Rd7, NR7C(═NRe7)NRc3Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, NRc7S(O)2Rb7, NRc7S(O)2NRc7Rd7, and S(O)2NRc7Rd7;
• Ra7, Rb7, Rc7, and Rd7 are independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-7 cycloalkyl-C1-4 alkyl, 5-10 membered heteroaryl-C1-4 alkyl, and 4-10 membered heterocycloalkyl-C1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-7 cycloalkyl-C1-4 alkyl, 5-10 membered heteroaryl-C1-4 alkyl, and 4-10 membered heterocycloalkyl-C1-4 alkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy;
• each Re, Re1, Rc2, Rc3, and R7 is independently selected from H, C1-4 alkyl, and CN;
• a is 0 or 1;
• m is 0 or 1;
• n is 0 or 1;
• p is 0 or 1;
• q is 0 or 1;
• r is 0 or 1;
• wherein any aforementioned heteroaryl or heterocycloalkyl group comprises 1, 2, 3, or 4 ring-forming heteroatoms independently selected from O, N, and S;
• and
• wherein one or more ring-forming C or N atoms of any aforementioned heterocycloalkyl group is optionally substituted by 1 or 2 oxo (═O) groups.