US 12,264,161 B2
Heterocyclic adenosine receptor antagonists
Sunghoon Ma, Foster City, CA (US); Yong Wang, South San Francisco, CA (US); and Wei Xu, Danville, CA (US)
Assigned to Exelixis, Inc., Alameda, CA (US)
Filed by Exelixis, Inc., Alameda, CA (US)
Filed on May 25, 2023, as Appl. No. 18/323,510.
Application 18/323,510 is a continuation of application No. 17/201,380, filed on Mar. 15, 2021, granted, now 11,718,622.
Claims priority of provisional application 62/990,105, filed on Mar. 16, 2020.
Prior Publication US 2023/0382917 A1, Nov. 30, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 487/04 (2006.01); A61K 31/4985 (2006.01); A61K 31/519 (2006.01); A61P 9/00 (2006.01); A61P 25/00 (2006.01); A61P 29/00 (2006.01); A61P 35/00 (2006.01); C07D 487/14 (2006.01); C07D 513/14 (2006.01)
CPC C07D 487/04 (2013.01) [C07D 487/14 (2013.01); C07D 513/14 (2013.01)] 20 Claims
 
1. A method of treating a disease or disorder in a patient,
the method comprising administering to the patient a therapeutically effective amount of a compound of formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
Ring A is heteroaryl or aryl, provided that Ring A is furanyl when R4 is H, aryl, or heteroaryl;
R1 is H or alkyl optionally substituted with 1, 2, 3, or 4 independently selected Ra substituents;
R2 is H, alkyl, —COR′″, —CONR′R″, —COOR′, —SO2R′, —SO2NR′R″, or —SO2OR′, wherein the alkyl of R2 is optionally substituted with 1, 2, 3, or 4 independently selected Ra substituents;
R3 is H, alkyl, halo, —CN, or —CONR′R″, wherein the alkyl of R3 is optionally substituted with 1, 2, 3, or 4 independently selected Ra substituents;
R4 is H, alkyl, halo, haloalkyl, —NR′R″, —COR′, —CONR′R″, —COOR′, SO2R′, —SO2NR′R″, —SO2OR′, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or —C1-4 alkylene-Rb, wherein Rb is cycloalkyl, heterocycloalkyl, aryl or heteroaryl, and wherein the alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or —C1-4 alkylene-Rb of R4 is optionally substituted with 1, 2, 3, or 4 independently selected Ra substituents;
each R5 is independently H, alkyl, halo, haloalkyl, alkoxy, —CN, —COR′, —CONR′R″, —COOR′, —SO2R′, —SO2NR′R″, —SO2OR′, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl wherein the alkyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl of R5 is optionally substituted with 1, 2, 3, or 4 independently selected Ra substituents;
n is 0, 1, 2, 3, 4, or 5;
one of Q1 and Q2 is N and the other is C;
Z is N or CR6;
R6 is H or alkyl, wherein the alkyl of R6 is optionally substituted with 1, 2, 3, or 4 independently selected Ra substituents;
R′ and R″ are each independently H or alkyl, wherein each alkyl of R′ and R″ is optionally substituted with 1, 2, 3, or 4 independently selected Ra substituents;
R′″ is alkyl, haloalkyl, cycloalkyl, or heterocycloalkyl, wherein the alkyl, cycloalkyl or heterocycloalkyl of R′″ is optionally substituted with 1, 2, 3, or 4 independently selected Ra substituents; and
each Ra is independently alkyl, halo, haloalkyl, hydroxy, alkoxy, hydroxyalkyl, cycloalkyl, or heterocycloalkyl, wherein each cycloalkyl and heterocycloalkyl of Ra is optionally and independently further substituted with 1, 2, or 3 of C1-4 alkyl, halo, C1-4 haloalkyl, hydroxy, or C1-4 alkoxy;
wherein the disease or disorder is associated with abnormal expression of A2A or A2B receptors, and wherein the disease or disorder is:
a cancer selected from the group consisting of lung cancer, non-small cell lung cancer, melanoma, malignant melanoma, renal cell cancer, triple negative breast cancer, colorectal cancer, bladder cancer, metastatic castration resistant prostate, cervical cancer, ovarian cancer, colorectal cancer, pancreatic cancer, esophageal cancer, prostate cancer, kidney cancer, skin cancer, thyroid cancer, liver cancer, and uterine cancer;
an inflammatory disease selected from the group consisting of a respiratory disorder, sepsis, reperfusion injury, and thrombosis;
a cardiovascular disease selected from the group consisting of coronary artery-disease, cerebrovascular disease, peripheral artery disease, aortic atherosclerosis, and aneurysm; or
Parkinson's disease.