US 12,403,145 B2
Substituted quinazolines for inhibiting kinase activity
Xiangping Qian, Foster City, CA (US); and Yong-Liang Zhu, Fremont, CA (US)
Assigned to NEUPHARMA, INC, San Mateo, CA (US)
Filed by NeuPharma, Inc, San Mateo, CA (US)
Filed on Nov. 27, 2023, as Appl. No. 18/519,150.
Application 17/681,387 is a division of application No. 16/843,610, filed on Apr. 8, 2020, granted, now 11,304,957, issued on Apr. 19, 2022.
Application 15/359,370 is a division of application No. 14/466,896, filed on Aug. 22, 2014, granted, now 9,550,770, issued on Jan. 24, 2017.
Application 18/519,150 is a continuation of application No. 17/681,387, filed on Feb. 25, 2022, granted, now 11,865,120.
Application 16/843,610 is a continuation of application No. 16/188,852, filed on Nov. 13, 2018, granted, now 10,653,701, issued on May 19, 2020.
Application 16/188,852 is a continuation of application No. 15/806,165, filed on Nov. 7, 2017, granted, now 10,172,868, issued on Jan. 8, 2019.
Application 15/806,165 is a continuation of application No. 15/359,370, filed on Nov. 22, 2016, granted, now 9,849,139, issued on Dec. 26, 2017.
Claims priority of provisional application 62/000,946, filed on May 20, 2014.
Claims priority of provisional application 61/900,283, filed on Nov. 5, 2013.
Claims priority of provisional application 61/869,596, filed on Aug. 23, 2013.
Prior Publication US 2024/0197752 A1, Jun. 20, 2024
Int. Cl. A61K 31/517 (2006.01); A61K 31/5377 (2006.01); A61K 31/553 (2006.01); A61K 45/06 (2006.01); C07C 57/145 (2006.01); C07D 239/84 (2006.01); C07D 401/04 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 403/04 (2006.01); C07D 403/12 (2006.01); C07D 405/12 (2006.01); C07D 413/12 (2006.01); C07D 471/04 (2006.01); C12Q 1/6886 (2018.01); G01N 33/574 (2006.01)
CPC A61K 31/553 (2013.01) [A61K 31/517 (2013.01); A61K 31/5377 (2013.01); A61K 45/06 (2013.01); C07C 57/145 (2013.01); C07D 239/84 (2013.01); C07D 401/04 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/04 (2013.01); C07D 403/12 (2013.01); C07D 405/12 (2013.01); C07D 413/12 (2013.01); C07D 471/04 (2013.01); C12Q 1/6886 (2013.01); G01N 33/57484 (2013.01); C12Q 2600/156 (2013.01); C12Q 2600/158 (2013.01)] 20 Claims
 
1. A compound of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
X3, X4, and X5 are one of the following:
(i) X3 is N; X4 is C—R13; X5 is C—R14;
(ii) X3 is C—R12; X4 is N; X5 is C—R14;
(iii) X3 is C—R12; X4 is C—R13; X5 is N; or
(iv) X3 is N; X4 is N; X5 is N;
n is 0, 1, 2, 3, 4, or 5;
m is 0, 1, 2, 3, 4, or 5;

OG Complex Work Unit Chemistry
is aryl or heteroaryl,

OG Complex Work Unit Chemistry
is aryl, heteroaryl, or heterocycloalkyl;
R6, R12, R13, R14, and each Z is independently hydrogen, cyano, halo, hydroxy, azido, nitro, carboxy, oxo, sulfinyl, sulfanyl, sulfonyl, optionally substituted alkoxy, optionally substituted cycloalkyloxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amino, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted aminosulfonyl, or optionally substituted carbamimidoyl, each Q is independently hydrogen, cyano, halo, hydroxy, azido, nitro, carboxy, oxo, sulfinyl, sulfanyl, sulfonyl, optionally substituted alkoxy, optionally substituted cycloalkyloxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amino, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted aminosulfonyl, optionally substituted carbamimidoyl, or E;
wherein E is an electrophilic group capable of forming a covalent bond with a nucleophile.