	US 12,391,642 B2
	Tetrahydro-1H-cyclopenta[cd]indene derivatives as hypoxia inducible factor-2(alpha) inhibitors
Jiping Fu, Danville, CA (US); Yan Lou, Dallas, TX (US); and Yigang He, Newark, DE (US)
Assigned to NiKang Therapeutics, Inc., Wilmington, DE (US)
Filed by NIKANG THERAPEUTICS, INC., Wilmington, DE (US)
Filed on Jul. 12, 2023, as Appl. No. 18/351,283.
Application 18/351,283 is a continuation of application No. 17/670,423, filed on Feb. 11, 2022, granted, now 11,753,366.
Application 17/670,423 is a continuation of application No. 17/218,129, filed on Mar. 30, 2021, granted, now 11,267,782, issued on Mar. 8, 2022.
Application 17/218,129 is a continuation of application No. 16/851,018, filed on Apr. 16, 2020, abandoned.
Claims priority of provisional application 62/946,191, filed on Dec. 10, 2019.
Claims priority of provisional application 62/836,019, filed on Apr. 18, 2019.
Prior Publication US 2023/0373909 A1, Nov. 23, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07C 255/54 (2006.01); A61K 31/277 (2006.01); A61K 31/4412 (2006.01); A61K 45/06 (2006.01); A61P 1/16 (2006.01); A61P 9/12 (2006.01); A61P 11/00 (2006.01); A61P 35/00 (2006.01); C07C 49/747 (2006.01); C07C 225/20 (2006.01); C07C 255/50 (2006.01); C07C 311/07 (2006.01); C07C 313/06 (2006.01); C07D 213/63 (2006.01); C07D 213/65 (2006.01); C07D 233/60 (2006.01)

CPC C07C 255/54 (2013.01) [A61P 35/00 (2018.01); C07C 313/06 (2013.01); C07D 213/63 (2013.01); C07D 233/60 (2013.01); A61K 45/06 (2013.01); C07C 2603/10 (2017.05); C07C 2603/97 (2017.05)]

19 Claims

1. A method of inhibiting or relieving cancer selected from a renal cancer, glioblastoma, neuroblastoma, paraganglioma, pheochromocytoma, pancreatic neuroendocrine tumors, colorectal cancer, somatostatinomas, hemangioblastomas, gastrointestinal stromal tumors, pituitary tumors, leiomyomas, leiomyosarcomas, polycythaemia, retinal cancers, von Hippel-Lindau disease, astrocytoma, lung cancer, melanoma, breast cancer, cervical cancer, head and neck cancer, ovarian cancer, prostate cancer, uterine leiomyomatosis, multiple myeloma, retinoblastoma, pancreatic endocrine tumors, squamous cell carcinoma, acute myeloid leukemia, myelodysplastic syndrome, and esophageal squamous cell carcinoma in a patient in need thereof which method comprises administering to the patient a therapeutically effective amount of a compound selected from the group consisting of:

3-fluoro-5-((1,3,3,4,4-pentafluoro-2a-hydroxy-2,2a,3,4-tetrahydro-1H-cyclopenta[cd]-inden-7-yl)oxy)benzonitrile, according to the following structure:

3-fluoro-5-((1,3,3,4,4-pentafluoro-2a-hydroxy-1-methyl-2,2a,3,4-tetrahydro-1H-cyclopenta[cd]inden-7-yl)oxy)benzonitrile, according to the following structure:

3-fluoro-5-(((1S,2aR)-1,3,3,4,4-pentafluoro-2a-hydroxy-2,2a,3,4-tetrahydro-1H-cyclopenta[cd]inden-7-yl-1,2,2-d3)oxy)benzonitrile, according to the following structure:

and

3-fluoro-5-(((1S,2aR)-1,3,3,4,4-pentafluoro-2a-hydroxy-2,2a,3,4-tetrahydro-1H-cyclopenta[cd]inden-7-yl-1-d) oxy)benzonitrile-2,4,6-d3, according to the following structure:

a pharmaceutically acceptable salt thereof.