Synthesis of 1-arylpiperazyl-2-phenylcyclopropanes designed as antidopaminergic agents: cyclopropane-based conformationally restricted analogs of haloperidol.
A series of the cyclopropane-based conformationally restricted analogs of haloperidol were designed as potential antidopaminergic agents and were effectively synthesized using highly stereoselective Grignard reaction with tert-butanesulfinyl imines as the key step. Pharmacological evaluation of the compounds showed that the conformational restriction method can effectively work for improving the pharmacological selectivity of a parent compound and also for investigating the bioactive conformation.
Yamaguchi
Kazuya
K
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Kazuta
Yuji
Y
Hirano
Kazufumi
K
Yamada
Shizuo
S
Matsuda
Akira
A
Shuto
Satoshi
S
D002073:Butanes / Q000737:chemistry; D003521:Cyclopropanes / Q000138:chemical synthesis / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D015195:Drug Design; D006220:Haloperidol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D007097:Imines / Q000737:chemistry; D008968:Molecular Conformation; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002073:Butanes; D003521:Cyclopropanes; D018492:Dopamine Antagonists; D007097:Imines; D010879:Piperazines; D006220:Haloperidol