Abstract
Provided herein are cyclohexane inhibitors of arginase, their pharmaceutical composition, and methods for using the compounds.
Important Compound Classes
Title
Arginase Inhibitors and Methods of Use Thereof
Patent Publication Number
WO 2022137156 A1
URI: https://patents.google.com/patent/WO2022137156A1/en?oq=WO+2022%2f137156+Al
Publication Date
June 30, 2022
Priority Application
US63/129,215
Priority Date
December 22, 2020
Inventors
Gzik, A.; Chrzanowski, J.; Blaszczyk, R.; Borek, B.; Olczak, J.; Golebiowski, A.; Grzybowski, M. M.; Pomper, P.; Güner-Chalimoniuk, N. C.; Lisiecki, K.; Kusmirek, D.
Assignee Company
Oncoarendi Therapeutics S.A., Poland
Disease Area
Cancer, cardiovascular disorders
Immune disorders
Biological Target
Arginase 1 and Arginase 2
Summary
The present invention describes a series of cyclohexane inhibitors of arginase as potential treatments for cancer, cardiovascular disorders, and immune disorders. Both arginase 1 (ARG1) and arginase 2 (ARG2) catalyze the hydrolysis of l-arginine into l-ornithine and urea. ARGl is a cytosolic protein, and ARG2 is mainly localized in mitochondria. The arginases are implicated in various pathological states including asthma, hypertension, erectile dysfunction, atherosclerosis, renal disease, ischemia, neurodegenerative diseases, fibrotic diseases, and cancer.
Key Structures
Biological Assay
The inhibitory activities of the compounds described in this invention were assessed using recombinant human arginases 1 and 2.
Biological Data
The following table shows IC50 values (nM) for the compounds tested for inhibition of arginases 1 and 2.
Claims
Thirty-six compounds are exemplified.
The author declares no competing financial interest.