The discovery and preparation of disubstituted novel amino-aryl-piperidine-based renin inhibitors.
Recently, trans-disubstituted oxo-aryl-piperidines have been identified as small molecule nonpeptide renin inhibitors for the modulation of hypertension. Herein, we report on the discovery and preparation of a new class of novel cis-disubstituted amino-aryl-piperidines as a mixture of enantiomers that are potent in vitro renin inhibitors and also, possess in vivo antihypertensive activity in a double transgenic mouse model.
Cody
Wayne L
WL
Department of Chemistry, Pfizer Global Research and Development, Michigan Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. wayne.cody@pfizer.com
Holsworth
Daniel D
DD
Powell
Noel A
NA
Jalaie
Mehran
M
Zhang
Erli
E
Wang
Wei
W
Samas
Brian
B
Bryant
John
J
Ostroski
Robert
R
Ryan
Michael J
MJ
Edmunds
Jeremy J
JJ
D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008822:Mice, Transgenic; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D000092502:Renin Inhibitors
D000959:Antihypertensive Agents; D010880:Piperidines; D000092502:Renin Inhibitors