US 11,926,632 B2
Methods and compounds for restoring mutant p53 function
Binh Vu, North Caldwell, NJ (US); Romyr Dominique, East Brunswick, NJ (US); Hongju Li, Edison, NJ (US); Bruce Fahr, East Windsor, NJ (US); and Yi Chen, Nutley, NJ (US)
Assigned to PMV Pharmaceuticals, Inc., Princeton, NJ (US)
Filed by PMV Pharmaceuticals, Inc., Cranbury, NJ (US)
Filed on Jun. 21, 2021, as Appl. No. 17/353,199.
Claims priority of provisional application 63/042,252, filed on Jun. 22, 2020.
Prior Publication US 2023/0046427 A1, Feb. 16, 2023
Int. Cl. C07D 487/10 (2006.01); C07C 237/40 (2006.01); C07D 213/36 (2006.01); C07D 213/38 (2006.01); C07D 213/73 (2006.01); C07D 213/81 (2006.01); C07D 215/12 (2006.01); C07D 231/56 (2006.01); C07D 239/42 (2006.01); C07D 401/04 (2006.01); C07D 401/12 (2006.01); C07D 405/12 (2006.01); C07D 413/12 (2006.01); C07D 417/12 (2006.01); C07D 487/08 (2006.01); C07D 491/107 (2006.01)
CPC C07D 487/10 (2013.01) [C07C 237/40 (2013.01); C07D 213/36 (2013.01); C07D 213/38 (2013.01); C07D 213/73 (2013.01); C07D 213/81 (2013.01); C07D 215/12 (2013.01); C07D 231/56 (2013.01); C07D 239/42 (2013.01); C07D 401/04 (2013.01); C07D 401/12 (2013.01); C07D 405/12 (2013.01); C07D 413/12 (2013.01); C07D 417/12 (2013.01); C07D 487/08 (2013.01); C07D 491/107 (2013.01)] 12 Claims
 
1. A compound of formula:

OG Complex Work Unit Chemistry
wherein:
X1 is CR7 or N;
R1 is alkyl that is unsubstituted or substituted, or —NR8R9, —C(O)NR8R9, —NR8C(O)R9, —OR10, —SR11, —C(O)R12, —C(O)OR12, —S(O)2R13, —CN, hydrogen, or halogen;
R2 is —OR10;
R3 is hydrogen;
R4 is alkyl, cycloalkyl, or straight or branched alkenyl, each of which is unsubstituted or substituted, or —C(O)R13, —C(O)OR13, —S(O)2R13, or hydrogen;
R5a, R5b, and R5d are each independently hydrogen or halogen;
each of R6a, R6b, R6c, R6d, and R6e is independently alkyl or cycloalkyl, each of which is unsubstituted or substituted, or —NR14R15, —OR16, —SR17, —C(O)NR14R15, —NR14C(O)R15, —CN, —C(O)OR18, —S(O)2R19, —NHS(O)2R19, hydrogen, or halogen; or R6a and R6b together with the carbon atoms to which R6a and R6b are bound form a ring, wherein the ring is unsubstituted or substituted, and each of R6c, R6d, and R6e is independently alkyl or cycloalkyl, each of which is unsubstituted or substituted, or —NR14R15, —OR16, —SR17, —C(O)NR14R15, —NR14C(O)R15, —CN, —C(O)OR18, —S(O)R19, —NHS(O)2R19, hydrogen, or halogen; or —R6b and R6c together with the carbon atoms to which R6b and R6c are bound form a ring, wherein the ring is unsubstituted or substituted, and each of Ra R66, and R6e is independently alkyl or cycloalkyl, each of which is unsubstituted or substituted, or —NR14R15, —OR16, —SR17, —C(O)NR14R15, —NR14C(O)R15, —CN, —C(O)OR18, —S(O)2R19, —NHS(O)2R19, hydrogen, or halogen: or R6c and R6d together with the carbon atoms to which R6c and R6d are bound form a ring, wherein the ring is unsubstituted or substituted, and each of R6a, R6b, and R6c is independently alkyl or cycloalkyl, each of which is unsubstituted or substituted, or —NR14R5, —OR16, —SR17, —C(O)NR14R15, —NR14C(O)R15, —CN, —C(O)OR18, —S(O)2R19, —NHS(O)2R19, hydrogen, or halogen; or R6d and R6e together with the carbon atoms to which R6d and R6e are bound form a ring, wherein the ring is unsubstituted or substituted, and each of R6a, R6b, and R6c is independently alkyl or cycloalkyl, each of which is unsubstituted or substituted, or —NR14R15, —OR16, —SR17, —C(O)NR14R15, —NR14C(O)R15, —CN, —C(O)OR18, —S(O)2R19, —NHS(O)2R19, hydrogen, or halogen;
R7 is alkyl, alkenyl, cycloalkyl, aryl, heteroaryl or heterocyclyl, each of which is unsubstituted or substituted, or hydrogen or halogen;
each of R8 and R9 is alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl, each of which is unsubstituted or substituted, or hydrogen; or R8 and R9 together with the atom(s) to which R8 and R9 are bound form a ring, wherein the ring is unsubstituted or substituted;
each of R10, R11, R12, and R13 is independently alkyl, alkenyl, cycloalkyl, aryl, heteroaryl or heterocyclyl, each of which is unsubstituted or substituted, or hydrogen or halogen;
each of R14 and R15 is independently alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl, each of which is unsubstituted or substituted, or hydrogen; and
each of R16, R17, R18, and R19 is independently alkyl, alkenyl, cycloalkyl, aryl, heteroaryl or heterocyclyl, each of which is unsubstituted or substituted, or hydrogen or halogen,
or a pharmaceutically-acceptable salt thereof.