title: Optimization of orally bioavailable alkyl amine renin inhibitors.
abstract: Structure-guided drug design led to new alkylamine renin inhibitors with improved in vitro and in vivo potency. Lead compound 21a, has an IC(50) of 0.83nM for the inhibition of human renin in plasma (PRA). Oral administration of 21a at 10mg/kg resulted in >20h reduction of blood pressure in a double transgenic rat model of hypertension.
authors: Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
authors: Zhenrong
authors: Z
authors: Xu
authors: Salvacion
authors: S
authors: Cacatian
authors: Jing
authors: J
authors: Yuan
authors: Robert D
authors: RD
authors: Simpson
authors: Lanqi
authors: L
authors: Jia
authors: Wei
authors: W
authors: Zhao
authors: Colin M
authors: CM
authors: Tice
authors: Patrick T
authors: PT
authors: Flaherty
authors: Joan
authors: J
authors: Guo
authors: Alexey
authors: A
authors: Ishchenko
authors: Suresh B
authors: SB
authors: Singh
authors: Zhongren
authors: Z
authors: Wu
authors: Brian M
authors: BM
authors: McKeever
authors: Boyd B
authors: BB
authors: Scott
authors: Yuri
authors: Y
authors: Bukhtiyarov
authors: Jennifer
authors: J
authors: Berbaum
authors: Jennifer
authors: J
authors: Mason
authors: Reshma
authors: R
authors: Panemangalore
authors: Maria Grazia
authors: MG
authors: Cappiello
authors: Ross
authors: R
authors: Bentley
authors: Christopher P
authors: CP
authors: Doe
authors: Richard K
authors: RK
authors: Harrison
authors: Gerard M
authors: GM
authors: McGeehan
authors: Lawrence W
authors: LW
authors: Dillard
authors: John J
authors: JJ
authors: Baldwin
authors: David A
authors: DA
authors: Claremon
mesh_terms: D000284:Administration, Oral; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001665:Binding Sites; D001794:Blood Pressure / Q000187:drug effects; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000882:Haplorhini; D006801:Humans; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D055647:Rats, Transgenic; D012083:Renin / Q000097:blood / Q000378:metabolism; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
chemical_list: D000588:Amines; D002219:Carbamates; D004791:Enzyme Inhibitors; D010880:Piperidines; D012083:Renin; D000092502:Renin Inhibitors