Novel selective hindlimb vasodilators: synthesis and biological activity of 1-acyl-4-aminopiperidine derivatives.
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.
Teramoto
Shuji
S
Medicinal Chemistry Research Institute, Otsuka Pharmaceutical Co, Ltd, 463-10 Kagasuno Kawauchi-cho, Tokushima 771-0192, Japan. stera@research.otsuka.co.jp
Tanaka
Michinori
M
Shimizu
Hiroshi
H
Fujioka
Takafumi
T
Tabusa
Fujio
F
Imaizumi
Takashi
T
Yoshida
Kenji
K
Fujiki
Hiroyuki
H
Mori
Toyoki
T
Sumida
Takumi
T
Tominaga
Michiaki
M
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
C476136:1-(3,5-dimethyl-4-propionylamino)benzoyl-4-(N-methyl-2-phenylethyl)aminopiperidine; D010880:Piperidines; D015363:Quinolones; D014665:Vasodilator Agents