US 11,807,658 B2
CD73 inhibitors
Xiaohui Du, Belmont, CA (US); John Eksterowicz, Burlingame, CA (US); Valeria R. Fantin, San Mateo, CA (US); Daqing Sun, Foster City, CA (US); Qiuping Ye, Foster City, CA (US); Jared Moore, San Rafael, CA (US); Tatiana Zavorotinskaya, Moraga, CA (US); Brian R. Blank, Daly City, CA (US); Yosup Rew, Foster City, CA (US); Kejia Wu, South San Francisco, CA (US); Liusheng Zhu, Foster City, CA (US); Johnny Pham, San Bruno, CA (US); and Hiroyuki Kawai, Pacifica, CA (US)
Assigned to ORIC PHARMACEUTICALS, INC., South San Francisco, CA (US)
Filed by ORIC Pharmaceuticals, Inc., South San Francisco, CA (US)
Filed on Mar. 17, 2022, as Appl. No. 17/697,318.
Application 17/697,318 is a continuation of application No. 17/078,567, filed on Oct. 23, 2020, granted, now 11,325,938.
Application 17/078,567 is a continuation of application No. PCT/US2019/030068, filed on Apr. 30, 2019.
Claims priority of provisional application 62/810,790, filed on Feb. 26, 2019.
Claims priority of provisional application 62/777,697, filed on Dec. 10, 2018.
Claims priority of provisional application 62/757,714, filed on Nov. 8, 2018.
Claims priority of provisional application 62/737,647, filed on Sep. 27, 2018.
Claims priority of provisional application 62/664,841, filed on Apr. 30, 2018.
Prior Publication US 2022/0220147 A1, Jul. 14, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07H 19/23 (2006.01); A61K 45/06 (2006.01)
CPC C07H 19/23 (2013.01) [A61K 45/06 (2013.01)] 19 Claims
 
1. A method of treating cancer in a subject, comprising administering to the subject a compound of Formula (IV), or a pharmaceutically acceptable salt thereof:
wherein:

OG Complex Work Unit Chemistry
Ring A is

OG Complex Work Unit Chemistry
Q2 is N or CW;
Q3 is N and Q4 is CW;
or Q3 is CW and Q4 is N;
each W is independently hydrogen, halogen, —CN, —ORb, NRcRd, C1-C6 alkyl, or C1-C6 haloalkyl;
A is —O— or —CH2—;
X is —O—, —S—, —S(═O)2—, —NR17—, or —C(R18)2—;
R1 and R2 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl), or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, Amyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently, optionally substituted with one, two, or three R1a;
or R1 and R2 are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three R1b;
each R1a and R1b is independently oxo (when feasible), halogen, —CN, —ORb, —SRb, —S(═O)Ra, —NO2, —NRcRd, —S(═O)2Ra, —NRbS(═O)2Ra, —S(═O)2NRcRd, —C(═O)ORb, —OC(═O)ORb; —C(═O)NRcRd, —OC(═O)NRcRd, —NRbC(═O)NRcRd, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl), or C1-C6 alkyl(heterocycloalkyl);
R3 is hydrogen, halogen, —CN, —ORb, —SRb, —NRcRd, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl), or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl; alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two; or three R3a;
each R3a is independently oxo (when feasible), halogen, —CN, —ORb, —NRcRd, —C(═O)Ra, —C(═O)ORb, —C(═O)NRcRd, C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl,
R4 and R7 are independently hydrogen, halogen, —ORb, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl; or heteroaryl;
R5 and R6 are independently hydrogen, halogen, —ORb, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
R8 is hydrogen, halogen, —ORb, —NRcRd, C1-C6 alkyl, or C1-C6 haloalkyl;
R9 and R10 are independently hydrogen, halogen, C1-C6 alkyl, or C1-C6 haloalkyl;
R11 is hydrogen, halogen, —CN, —OR13, —SR13, —S(═O)R14, —NO2, —NR15R16, —S(═O)2R14, —NR13S(═O)2R14, —S(═O)2NR15R16, —C(═O)R14, —OC(═O)R14, —C(═O)OR13, —OC(═O)OR13, NR13C(═O)OR13, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R11a;
R12 is halogen, —CN, —OR13, —SR13, —S(═O)R14, —NO2, —NR15R16, —S(═O)2R14, —NR13S(═)2R14, —S(═)2NR15R16, —C(═O)R14, —OC(═O)R14, —C(═O)OR13, —OC(═O)OR13, —C(═O)NR15R16, —OC(═O)NR15R16, —NR13C(═O)NR15R16, —NR13C(═O)R14, —NR13C(═O)OR13, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R12a;
or R11 and R12 are taken together to form a cycloalkyl or heterocycloalkyl each optionally substituted with one, two, or three R11b;
each R11a, R11b, and R12a is independently oxo (when feasible), halogen, —CN, —OR13, —SR13, —S(═O)R14, —NO2, —NR15R16, —S(═O)2R14, —NR13S(═O)2R14, —S(═O)2NR15R16, —C(═O)R14, —OC(═O)R14, —C(═O)OR13, —OC(═O)OR13, —C(═O)NR15R16, —OC(═O)NR15R16, —NR13C(═O)NR15R16, —NR13C(═O)R14, —NR13C(═O)OR13, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R11c;
each R11c is independently oxo (when feasible), halogen, —CN, —ORb, —SRb, —S(═O)Ra, —NO2, —NRcRd, —S(═)2Ra, —NRbS(═O)2Ra, —S(═O)2NRcRd, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRcRd, —OC(═O)NRcRd, —NRbC(═O)NRcRd, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl), or C1-C6 alkyl(heterocycloalkyl);
each R13 is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R13a;
each R14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R14a;
each R15 and R16 is independently hydrogen, C1-C6 alkyl; C1-C6 haloalkyl, alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R15a;
or R15 and R16 are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three R15b;
each R13a, R14a, R15a, and R15b is independently oxo (when feasible), halogen, —CN, —ORb, —SRb, —S(═O)Ra, —NO2, —NRcRd, —S(═O)2Ra, —NHS(═O)2Ra, —S(═O)2NRcRd, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRcRd, —OC(50 O)NRcRd, —NRbC(═O)NRcRd, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl; C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl), or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three oxo (when feasible), halogen, —CN, —ORb, —S(═O)Ra, —NO2, —NRcRd; —S(═O)2Ra, —S(═O)2NRcRd, —C(═O)Ra, —C(═O)ORb, —C(═O)NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, or C2-C6 alkynyl;
R17 is hydrogen, —CN, —ORb, —S(═O)2Ra, —C(═O)Ra, —C(═O)ORb; —C(═O)NRa, C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl), or C1-C6 alkyl(heterocycloalkyl);
each R18 is independently hydrogen, halogen, —CN, —ORb, —SRb, —S(═O)Ra, —NO2, —NRcRd, —S(═O)2Ra, —NHS(═O)2Ra, —S(═O)2NRcRd, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRcRd, —OC(═O)NRcRd, —NRbC(═O)NRcRd, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl), or C1-C6 alkyl(heterocycloalkyl);
R21 and R22 are independently hydrogen, C1-C20 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R21a;
or R21 and R22 are taken together with the atoms to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three R21b;
each R21a and R21b is independently oxo (when feasible), halogen, —CN, —ORb, —SRb, —S(═O)Ra, —NO2, —NRcRd, —S(═O)2Ra, —NHS(═O)2Ra, —S(═O)2NRcRd, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRcRd, —OC(═O)NRcRd, —NRbC(═O)NRcRd, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl), or C1-C6 alkyl(heterocycloalkyl);
each Ra is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three oxo (when feasible), halogen, —OH, C1-C6 alkyl, or C1-C6 haloalkyl;
each Rb is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three oxo (when feasible), halogen, —OH, C1-C6 alkyl, or C1-C6 haloalkyl; and
each Rc and Rd is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three oxo (when feasible), halogen, —OH, C1-C6 alkyl, or C1-C6 haloalkyl;
or Rc and Rd are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three oxo, halogen, C1-C6 or C1-C6 haloalkyl; and wherein the cancer is selected from lung cancer, melanoma, breast cancer, ovarian cancer, colorectal cancer, gastric cancer, gallbladder cancer, prostate cancer, renal cancer, multiple myeloma, and lymphoma.