title: Novel selective hindlimb vasodilators: synthesis and biological activity of 1-acyl-4-aminopiperidine derivatives.
abstract: A series of 6-(4-amino-1-piperidinyl)carbonyl-2(1H)-quinolinones, and their open form derivatives, were synthesized and evaluated for their ability to stimulate femoral artery blood flow (FBF) in the canine hindlimb. All members of this series stimulated FBF, and subsequent experiments revealed that selected members of this series produced minimal changes in coronary blood flow or systemic blood pressure. Compound 25 was the most promising agent in this respect, and clinical trials are now ongoing to evaluate the effectiveness of this drug as a novel treatment for intermittent claudication and Raynaud's phenomenon.
authors.affiliation: Medicinal Chemistry Research Institute, Otsuka Pharmaceutical Co, Ltd, 463-10 Kagasuno Kawauchi-cho, Tokushima 771-0192, Japan. stera@research.otsuka.co.jp
authors.forename: Shuji
authors.initials: S
authors.lastname: Teramoto
authors.forename: Michinori
authors.initials: M
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Takafumi
authors.initials: T
authors.lastname: Fujioka
authors.forename: Fujio
authors.initials: F
authors.lastname: Tabusa
authors.forename: Takashi
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujiki
authors.forename: Toyoki
authors.initials: T
authors.lastname: Mori
authors.forename: Takumi
authors.initials: T
authors.lastname: Sumida
authors.forename: Michiaki
authors.initials: M
authors.lastname: Tominaga
mesh_terms: D000818:Animals; D001158:Arteries; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005269:Femur / Q000098:blood supply; D006614:Hindlimb / Q000098:blood supply*; D066298:In Vitro Techniques; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C476136:1-(3,5-dimethyl-4-propionylamino)benzoyl-4-(N-methyl-2-phenylethyl)aminopiperidine; D010880:Piperidines; D015363:Quinolones; D014665:Vasodilator Agents