Synthesis and pharmacological evaluation of (nitrooxy)alkyl apovincaminates.
A series of (nitrooxy)alkyl apovincaminates has been synthesized and evaluated for their effects on vertebral and femoral blood flow. These derivatives were prepared from apovincaminic acid (4). In cerebral circulation, compound 5 (0.03-1.0 mg/kg iv) caused a dose-dependent increase in cerebral blood flow (CerBF) without affecting the blood pressure. It was more potent than vinpocetine (2). The structures of 2 and 5, determined by X-ray crystallography, showed differences in the electrostatic potential image and in the conformation of the ethyl group at the 16-position.
Kawashima
Y
Y
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Ikemoto
T
T
Horiguchi
A
A
Hayashi
M
M
Matsumoto
K
K
Kawarasaki
K
K
Yamazaki
R
R
Okuyama
S
S
Hatayama
K
K
D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003461:Crystallography; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009574:Nitro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014748:Vinca Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014749:Vincamine / Q000031:analogs & derivatives* / Q000494:pharmacology
D009574:Nitro Compounds; D014665:Vasodilator Agents; D014748:Vinca Alkaloids; C081044:2-(nitrooxy)ethyl apovincaminate; C013983:vinpocetine; D014749:Vincamine