title: Design and optimization of renin inhibitors: Orally bioavailable alkyl amines.
abstract: Structure-based drug design led to the identification of a novel class of potent, low MW alkylamine renin inhibitors. Oral administration of lead compound 21l, with MW of 508 and IC(50) of 0.47nM, caused a sustained reduction in mean arterial blood pressure in a double transgenic rat model of hypertension.
authors.affiliation: Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA. ctice@vitaerx.com
authors.forename: Colin M
authors.initials: CM
authors.lastname: Tice
authors.forename: Zhenrong
authors.initials: Z
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Robert D
authors.initials: RD
authors.lastname: Simpson
authors.forename: Salvacion T
authors.initials: ST
authors.lastname: Cacatian
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Flaherty
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Joan
authors.initials: J
authors.lastname: Guo
authors.forename: Alexey
authors.initials: A
authors.lastname: Ishchenko
authors.forename: Suresh B
authors.initials: SB
authors.lastname: Singh
authors.forename: Zhongren
authors.initials: Z
authors.lastname: Wu
authors.forename: Boyd B
authors.initials: BB
authors.lastname: Scott
authors.forename: Yuri
authors.initials: Y
authors.lastname: Bukhtiyarov
authors.forename: Jennifer
authors.initials: J
authors.lastname: Berbaum
authors.forename: Jennifer
authors.initials: J
authors.lastname: Mason
authors.forename: Reshma
authors.initials: R
authors.lastname: Panemangalore
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cappiello
authors.forename: Dominik
authors.initials: D
authors.lastname: Müller
authors.forename: Richard K
authors.initials: RK
authors.lastname: Harrison
authors.forename: Gerard M
authors.initials: GM
authors.lastname: McGeehan
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Dillard
authors.forename: John J
authors.initials: JJ
authors.lastname: Baldwin
authors.forename: David A
authors.initials: DA
authors.lastname: Claremon
mesh_terms: D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D001794:Blood Pressure; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D008744:Methylamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D055647:Rats, Transgenic; D012083:Renin / Q000378:metabolism; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
chemical_list: D000959:Antihypertensive Agents; D008744:Methylamines; D012083:Renin; D000092502:Renin Inhibitors