首页|3,4-二氢喹啉-2(1H)-酮衍生物(±)-SIPI6360及其光学异构体的合成和药理学评价

3,4-二氢喹啉-2(1H)-酮衍生物(±)-SIPI6360及其光学异构体的合成和药理学评价

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7-[3-[4-(6-氟苯并[d]异噁唑-3-基)哌啶-1-基]丙氧基]-3-甲基-3,4-二氢喹啉-2(1H)-酮[(±)-SIPI6360]为本课题组发现的多靶点抗精神分裂症候选新药,其化学结构中存在一个手性中心.本试验报道了(±)-SIPI6360及其2个光学异构体的制备和体内外药理性能的比较研究.结果 显示,(±)-SIP16360及其光学异构体的体内外药效、大鼠体内药动学特性及毒性方面无显著性差别.基于原料制备成本,确定(±)-SIPI6360消旋体作为抗精神分裂症候选新药的更优结构.
Synthesis and Pharmacological Evaluation of a 3,4-Dihydroquinolin-2 (1H)-ketone Derivative (±)-SIPI6360 and Its Optical Isomers
7-[3-[4-(6-Fluorobenzo [d] isoxazol-3-y1) piperidin-1-y1] propoxy]-3-methy1-3,4-dihydroquinolin-2 (1H)-one[(±)-SIPI6360] is a multireceptor antipsychotic candidate discovered by our research group.It has two optical isomers because of a chiral carbon atom at the 3,4-dihydroquinoline segment.The synthesis,in vitro and in vivo pharmacology,pharmacokinetics in rats,and repeat-dose toxicity (14 days) in rats of (±)-SIPI6360 and its two optical isomers were reported.No significant differences among (±)-SIPI6360 and its two optical isomers were found regarding to the efficacy,metabolic parameters and toxic effects.Thus,(±)-SIPI6360 was chosen as the candidate for potential psychotic treatment based upon preparation cost.

antipsychoticsoptical isomersynthesispharmacological evaluation

齐阳历、陈晓文、许珺玮、倪峰、李建其

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复旦大学药学院,上海201203

中国医药工业研究总院上海医药工业研究院,化学制药新技术中心,上海201203

抗精神分裂症药 光学异构体 合成 药理评价

National Natural Science Foundation of ChinaKey Technologies R&D Program of Shanghai Municipal Science and Technology Commission (GShanghai Rising-Star Programand the National Science and Te

818033711743190380019QB1406200

2020

中国医药工业杂志
上海医药工业研究院,中国化学制药工业协会

中国医药工业杂志

CSTPCDCSCD北大核心EI
影响因子：0.487
ISSN：1001-8255
年,卷(期)：2020.51(2)
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