US 12,435,030 B2
PCNA inhibitors
Linda H. Malkas, Lakeview Terrace, CA (US); David Horne, Altadena, CA (US); Robert J. Hickey, Lakeview Terrace, CA (US); and Long Gu, Arcadia, CA (US)
Assigned to City of Hope, Duarte, CA (US)
Filed by City of Hope, Duarte, CA (US)
Filed on Jun. 26, 2024, as Appl. No. 18/755,058.
Application 18/755,058 is a continuation of application No. 17/730,948, filed on Apr. 27, 2022, granted, now 12,054,447.
Application 17/730,948 is a continuation of application No. 17/108,739, filed on Dec. 1, 2020, granted, now 11,345,656, issued on May 31, 2022.
Application 17/108,739 is a continuation of application No. 16/714,062, filed on Dec. 13, 2019, granted, now 10,913,706, issued on Feb. 9, 2021.
Application 16/714,062 is a continuation of application No. 15/760,959, granted, now 10,550,070, issued on Feb. 4, 2020, previously published as PCT/US2016/052310, filed on Sep. 16, 2016.
Claims priority of provisional application 62/340,964, filed on May 24, 2016.
Claims priority of provisional application 62/313,592, filed on Mar. 25, 2016.
Claims priority of provisional application 62/220,014, filed on Sep. 17, 2015.
Prior Publication US 2024/0343682 A1, Oct. 17, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07C 233/76 (2006.01); A61K 31/167 (2006.01); A61K 31/4409 (2006.01); A61K 31/4418 (2006.01); A61K 31/4725 (2006.01); A61K 33/243 (2019.01); A61P 35/00 (2006.01); A61P 35/02 (2006.01); C07C 237/22 (2006.01); C07D 213/68 (2006.01); C07D 217/26 (2006.01); C07D 401/12 (2006.01)
CPC C07C 233/76 (2013.01) [A61K 31/167 (2013.01); A61K 31/4409 (2013.01); A61K 31/4418 (2013.01); A61K 31/4725 (2013.01); A61K 33/243 (2019.01); A61P 35/00 (2018.01); A61P 35/02 (2018.01); C07C 237/22 (2013.01); C07D 213/68 (2013.01); C07D 217/26 (2013.01); C07D 401/12 (2013.01)] 20 Claims
 
1. A pharmaceutical composition comprising a compound, an anti-cancer agent, and a pharmaceutically acceptable excipient, wherein the anti-cancer agent is a platinum-based compound, topoisomerase inhibitor, EGFR inhibitor, ras inhibitor, MEK inhibitor, signal transduction inhibitor, or signal transduction modulator; and
wherein the compound has the formula:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof; wherein
Ring A is substituted or unsubstituted phenyl or substituted or unsubstituted 5 to 6 membered heteroaryl;
Ring B is substituted or unsubstituted 1-naphthyl, or substituted or unsubstituted isoquinolinyl;
R1 is independently a halogen, —CX13, —CHX12, —CH2X1, —CN, —SOn1R10, —SOv1NR7R8, —NHNH2, —ONR7R8, —NHC═(O)NHNH2, —NHC═(O)NR7R8, —N(O)m1, —NR7R8, —C(O)R9, —C(O)—OR9, —C(O)NR7R8, —OR10, —NR7SO2R10, —NR7C═(O)R9, —NR7C(O)—OR9, —NR7OR9, —OCX13, —OCHX12, —OCH2X1, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or two adjacent R1 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R2 is independently hydrogen, halogen, —CX23, —CHX22, —CH2X2, —CN, —COOH, —CONH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R3 is independently hydrogen, halogen, —CX33, —CHX32, —CH2X3, —CN, —COOH, —CONH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R7, R8, R9, and R10 are independently hydrogen, halogen, —CXA3, —CHXA2, —CH2XA, —CN, —COOH, —CONH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or R7 and R8 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
z1 is an integer from 0 to 4;
m1 and v1 are independently 1 or 2;
n1 is independently an integer from 0 to 4; and
X1, X2, X3, and XA are independently —Cl, —Br, —I, or —F.