Back to Search Start Over

Discovery of Triazole CYP11B2 Inhibitors with in Vivo Activity in Rhesus Monkeys.

Authors :
Hoyt SB
Petrilli W
London C
Liang GB
Tata J
Hu Q
Yin L
van Koppen CJ
Hartmann RW
Struthers M
Wisniewski T
Ren N
Bopp C
Sok A
Cai TQ
Stribling S
Pai LY
Ma X
Metzger J
Verras A
McMasters D
Chen Q
Tung E
Tang W
Salituro G
Buist N
Clemas J
Zhou G
Gibson J
Maxwell CA
Lassman M
McLaughlin T
Castro-Perez J
Szeto D
Forrest G
Hajdu R
Rosenbach M
Xiong Y
Source :
ACS medicinal chemistry letters [ACS Med Chem Lett] 2015 Jul 17; Vol. 6 (8), pp. 861-5. Date of Electronic Publication: 2015 Jul 17 (Print Publication: 2015).
Publication Year :
2015

Abstract

Hit-to-lead efforts resulted in the discovery of compound 19, a potent CYP11B2 inhibitor that displays high selectivity vs related CYPs, good pharmacokinetic properties in rat and rhesus, and lead-like physical properties. In a rhesus pharmacodynamic model, compound 19 displays robust, dose-dependent aldosterone lowering efficacy, with no apparent effect on cortisol levels.

Details

Language :
English
ISSN :
1948-5875
Volume :
6
Issue :
8
Database :
MEDLINE
Journal :
ACS medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
26288685
Full Text :
https://doi.org/10.1021/acsmedchemlett.5b00048