Synthesis and pharmacological evaluation of piperidine (piperazine)-substituted benzoxazole derivatives as multi-target antipsychotics.
The present study describes the optimization of a series of novel benzoxazole-piperidine (piperazine) derivatives combining high dopamine D2 and serotonin 5-HT1A, 5-HT2A receptor affinities. Of these derivatives, the pharmacological features of compound 29 exhibited high affinities for the DA D2, 5-HT1A and 5-HT2A receptors, but low affinities for the 5-HT2C and histamine H1 receptors and human ether-a-go-go-related gene (hERG) channels. Furthermore, compound 29 reduced apomorphine-induced climbing and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head twitching without observable catalepsy, even at the highest dose tested. Thus, compound 29 is a promising candidate as a multi-target antipsychotic treatment.
Wuhan Docan Pharmaceutical Co., Ltd, Wuhan 430040, China; Pharmacy School of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Ling
L
Huang
Wuhan Docan Pharmaceutical Co., Ltd, Wuhan 430040, China.
Wenjun
W
Zhang
Wuhan Docan Pharmaceutical Co., Ltd, Wuhan 430040, China.
Xiaohua
X
Zhang
Wuhan Docan Pharmaceutical Co., Ltd, Wuhan 430040, China.
Lei
L
Yin
Pharmacy School of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Bangyin
B
Chen
Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address: songjcwhu@163.com.
Jinchun
J
Song
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors; D006801:Humans; D051379:Mice; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D026902:Potassium Channel Blockers / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000819:agonists; D012559:Schizophrenia / Q000188:drug therapy*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D058826:Serotonin 5-HT2 Receptor Agonists / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship; D013552:Swine
C000608575:3-(1-(3-(4-(benzo(d)oxazol-2-ylmethyl)phenoxy)propyl)piperidin-4-yl)-6-fluorobenzo(d)isoxazole; D014150:Antipsychotic Agents; D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; D010080:Oxazoles; D010879:Piperazines; D010880:Piperidines; D026902:Potassium Channel Blockers; D017448:Receptors, Dopamine D2; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists
Antipsychotic; Benzoxazole; Piperazine; Piperidine