Synthesis and structure-activity relationships of 2-(4-benzhydryl-1-piperazinyl)-1-phenylethanols as new calcium blockers.
A series of 2-(4-benzhydryl-1-piperazinyl)-1-phenylethanols (4) was synthesized and evaluated for calcium entry-blocking activity, assessed as inhibitory activity on calcium current in rat hippocampal pyramidal neurons by using a patch-clamp technique (10(-5) M), and cerebral vasodilating activity, assessed in terms of increase of vertebral blood flow after intravenous administration (1 mg/kg) in anesthetized dogs. Alkoxy substituents on the phenyl ring of the phenylethanol moiety conferred potent calcium entry-blocking activity and potent cerebral vasodilating activity. Among these compounds, 4i (NC-1100) was selected as the best analog. Some pharmacological properties of 4i are presented.
Nomura
Y
Y
Department of Applied Chemistry, Faculty of Engineering, Saitama University, Japan.
Yamakawa
T
T
Nishioka
K
K
Omura
T
T
Miyake
N
N
Masaki
M
M
Nohira
H
H
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004285:Dogs; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives*; D010879:Piperazines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D013115:Spinal Canal / Q000098:blood supply / Q000187:drug effects; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D010879:Piperazines; D014665:Vasodilator Agents; C050134:tamolarizine; D010626:Phenylethyl Alcohol