US 11,787,813 B2
Substituted pyrazolopyrimidines and substituted purines and their use as ubiquitin-specific-processing protease 1 (USP1) inhibitors
Jehrod Burnett Brenneman, Marblehead, MA (US); Elsa Beyer Krall, Cambridge, MA (US); Michael Schlabach, Belmont, MA (US); and Andrew Alistair Wylie, Newton, MA (US)
Assigned to KSQ Therapeutics, Inc., Lexington, MA (US)
Filed by KSQ Therapeutics, Inc., Lexington, MA (US)
Filed on Oct. 11, 2022, as Appl. No. 18/45,770.
Application 18/045,770 is a division of application No. 16/721,079, filed on Dec. 19, 2019, granted, now 11,485,736.
Claims priority of provisional application 62/946,263, filed on Dec. 10, 2019.
Claims priority of provisional application 62/868,616, filed on Jun. 28, 2019.
Claims priority of provisional application 62/857,986, filed on Jun. 6, 2019.
Claims priority of provisional application 62/799,423, filed on Jan. 31, 2019.
Claims priority of provisional application 62/783,014, filed on Dec. 20, 2018.
Prior Publication US 2023/0203046 A1, Jun. 29, 2023
Int. Cl. C07D 487/04 (2006.01); A61P 35/00 (2006.01); C12Q 1/6886 (2018.01)
CPC C07D 487/04 (2013.01) [A61P 35/00 (2018.01); C12Q 1/6886 (2013.01); C12Q 2600/156 (2013.01)] 30 Claims
 
1. A method of treating cancer in a patient comprising administering to the patient a therapeutically effective amount of a compound having Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or solvate thereof, wherein:

OG Complex Work Unit Chemistry
each of R1 and R2 is independently selected from hydrogen, halo, cyano, optionally substituted alkyl, optionally substituted alkenyl, and optionally substituted alkynyl;
R3 is an optionally substituted phenyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, optionally substituted pyrazinyl, optionally substituted pyridazinyl, or optionally substituted pyrazolyl;
each of X11 and X12 is independently selected from N and CH;
R5′ is selected from hydrogen, optionally substituted (C1-C6) alkyl, optionally substituted (C2-C6) alkenyl, optionally substituted (C2-C6) alkynyl, optionally substituted (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, cyano, halo, sulfonamido, —C(═O)R23, —C(═O)OR24, —NR32aR32b, —NR31aC(═O)R25, —NR31aC(═O)NR31aR31b, —C(═O)NR31aR31b, —S(O)2R27, —NR31aSO2R27, optionally substituted (C6-C14) aryl, optionally substituted (C6-C14) ar-(C1-C2) alkyl, optionally substituted heteroaryl, optionally substituted heteroar-(C1-C2) alkyl, optionally substituted (C3-C8) cycloalkyl, optionally substituted ((C3-C8) cycloalkyl)-(C1-C2) alkyl, optionally substituted heterocyclo, optionally substituted heterocyclo-(C1-C2) alkyl, optionally substituted —O—(C6-C14) aryl, optionally substituted —O—(C6-C14) ar-(C1-C2) alkyl, optionally substituted —O-heteroaryl, optionally substituted —O-heteroar-(C1-C2) alkyl, optionally substituted —O—(C3-C8) cycloalkyl, optionally substituted —O—((C3-C8) cycloalkyl)-(C1-C2) alkyl, optionally substituted —O-heterocyclo, optionally substituted —O-heterocyclo-(C1-C2) alkyl;
R5 is selected from optionally substituted (C1-C6) alkyl, optionally substituted (C2-C6) alkenyl, optionally substituted (C2-C6) alkynyl, optionally substituted (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, cyano, halo, sulfonamido, —C(═O)R23, —C(═O)OR24, —NR32aR32b, —NR31aC(═O)R25, —NR31aC(═O)NR31aR31a(═O)NR31aR31b, —S(O)2R27, —NR31aSO2R27, optionally substituted (C6-C14) aryl, optionally substituted (C6-C14) ar-(C1-C2) alkyl, optionally substituted heteroaryl, optionally substituted heteroar-(C1-C2) alkyl, optionally substituted (C3-C8) cycloalkyl, optionally substituted ((C3-C8) cycloalkyl)-(C1-C2) alkyl, optionally substituted heterocyclo, optionally substituted heterocyclo-(C1-C2) alkyl, optionally substituted —O—(C6-C14) aryl, optionally substituted —O—(C6-C14) ar-(C1-C2) alkyl, optionally substituted —O-heteroaryl, optionally substituted —O-heteroar-(C1-C2) alkyl, optionally substituted —O—(C3-C8) cycloalkyl, optionally substituted —O—((C3-C8) cycloalkyl)-(C1-C2) alkyl, optionally substituted —O-heterocyclo, optionally substituted —O-heterocyclo-(C1-C2) alkyl; or
one of R5 and one of R5′ on adjacent atoms are taken together with the atoms to which they are attached to form an optionally substituted (C6-C14) aryl ring; or one of R5 and one of R5′ on adjacent atoms are taken together with the atoms to which they are attached to form an optionally substituted heteroaryl ring; or one of R5 and one of R5′ on adjacent atoms are taken together with the atoms to which they are attached to form an optionally substituted (C3-C8) cycloalkyl ring; or one of R5 and one of R5′ on adjacent atoms are taken together with the atoms to which they are attached to form an optionally substituted heterocycloalkyl ring; or one of R5 and one of R5′ on adjacent atoms on the same atom to which they are attached are taken together to form an optionally substituted spirocycloalkyl ring; or one of R5 and one of R5′ on adjacent atoms on the same atom to which they are attached are taken together to form an optionally substituted spiroheterocycloalkyl ring;
each of R6 and R7 is independently selected from hydrogen, halo, cyano, optionally substituted alkyl, optionally substituted alkenyl, and optionally substituted alkynyl;
R23 is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, amino, alkylamino, dialkylamino, cycloalkylamino, hydroxyalkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, (cycloalkylamino)alkyl, (cycloalkyl)alkyl, aralkyl, (heterocyclo)alkyl, (heteroaryl)alkyl, (amino)(hydroxy)alkyl, (aralkylamino)alkyl, optionally substituted heterocyclo, optionally substituted heteroaryl, optionally substituted aryl, and optionally substituted cycloalkyl;
R31a and R31b are each independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, hydroxyalkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, alkoxyalkyl, cycloalkyl, (cycloalkyl)alkyl, (heterocyclo)alkyl, aralkyl, and (heteroaryl)alkyl; and
each of R24, R25, R27, R32a, and R32b is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, amino, alkylamino, dialkylamino, cycloalkylamino, hydroxyalkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, (cycloalkylamino)alkyl, (cycloalkyl)alkyl, aralkyl, (heterocyclo)alkyl, (heteroaryl)alkyl, (amino)(hydroxy)alkyl, (aralkylamino)alkyl, alkoxyalkyl, optionally substituted heterocyclo, optionally substituted heteroaryl, optionally substituted aryl, and optionally substituted cycloalkyl.