Benzoxazepine-Derived Selective, Orally Bioavailable Inhibitor of Human Acidic Mammalian Chitinase.
ACS Med Chem Lett
; 11(6): 1228-1235, 2020 Jun 11.
Article
in En
| MEDLINE
| ID: mdl-32551005
ABSTRACT
Human acidic mammalian chitinase (hAMCase) is one of two true chitinases in humans, the function of which remains elusive. In addition to the defense against highly antigenic chitin and chitin-containing pathogens in the gastric and intestinal contents, AMCase has been implicated in asthma, allergic inflammation, and ocular pathologies. Potent and selective small-molecule inhibitors of this enzyme have not been identified to date. Here we describe structural modifications of compound OAT-177, a previously developed inhibitor of mouse AMCase, leading to OAT-1441, which displays high activity and selectivity toward hAMCase. Significantly reduced off-target activity toward the human ether-à-go-go-related gene (hERG) and a good pharmacokinetic profile make OAT-1441 a potential candidate for further preclinical development as well as a useful tool compound to study the physiological role of hAMCase.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
ACS Med Chem Lett
Year:
2020
Document type:
Article
Affiliation country:
Polonia