Discovery of a potent and selective alpha v beta 3 integrin antagonist with strong inhibitory activity against neointima formation in rat balloon injury model.
A new series of phenylpiperazine-based derivatives with strong antagonistic activity for alpha v beta 3 integrin were synthesized. Of these derivatives, the fluorine-substituted compound 8 showed strong inhibitory activity and high selectivity for alpha v beta 3 integrin receptor (IC(50) = 0.055 nM). In vivo evaluation of the antistenotic effects of 8 indicated that this compound significantly inhibits neointima formation in rat balloon injury model.
Iwama
Seiji
S
Chemistry Research Laboratories, Dainippon Pharmaceutical Co., Ltd, Enoki 33-94, Suita, Osaka 564-0053, Japan. seiji-iwama@dainippon-pharm.co.jp
Kitano
Tomoko
T
Fukuya
Fumiyo
F
Honda
Yayoi
Y
Sato
Yuji
Y
Notake
Mitsue
M
Morie
Toshiya
T
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects; D003251:Constriction, Pathologic / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010879:Piperazines / Q000097:blood / Q000138:chemical synthesis / Q000627:therapeutic use*; D051381:Rats; D017539:Tunica Intima / Q000187:drug effects* / Q000254:growth & development
D039302:Integrin alphaVbeta3; D010879:Piperazines; C031503:phenylpiperazine