一种新型钙拮抗剂（+）-（R）-3,4-二氢-2-[5-甲氧基-2-[3-[N-甲基-N-[2-[(3,4-亚甲二氧基)苯氧基]乙基]氨基]丙氧基]苯基]-4-甲基-3-氧代-2H-1,4-苯并噻嗪（SD-3211）在大鼠体内粪便代谢产物的合成及其钙拮抗活性

[Synthesis and calcium antagonistic activities of fecal metabolites of a new calcium antagonist (+)-(R)-3,4-dihydro-2-[5-methoxy-2-[3-[N-methyl-N- [2-[(3,4-methylenedioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4- methyl-3-oxo-2H-1,4-benzothiazine (SD-3211) in rats].

作者信息

Fujita M, Ito S, Suhara H, Ibuki H, Kawashima Y

机构信息

Central Research Laboratories, Santen Pharmaceutical Co., Ltd., Osaka, Japan.

出版信息

Yakugaku Zasshi. 1991 Jan;111(1):59-64. doi: 10.1248/yakushi1947.111.1_59.

DOI:10.1248/yakushi1947.111.1_59

PMID:2056445

Abstract

In order to confirm the structure of three fecal metabolites, M-I, M-II and M-III, of a new calcium antagonist, (+)-3,4-dihydro-2-[5-methoxy-2-[3-[N-methyl-N-[2-[(3,4-methylenedioxy) phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-3-oxo-2H-1,4- benzothiazine (SD-3211), in rats, (+)-3,4-dihydro-2-[5-hydroxy-2-[3-[N-methyl-N-[2- [(3,4-methylenedioxy)-phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl- 3-oxo-2H-1,4-benzothiazine((+)-I), (+)-3,4-dihydro-2-[5-hydroxy-2-[3-[N- [2-[(3,4-methylenedioxy) phenoxy]ethyl]amino] propoxy]-phenyl]-4-methyl-3-oxo-2H-1,4-benzothiazine((+)-II) and (+)-3,4-dihydro-2-[5-methoxy-2-[3-[N-[2-[(3,4-methylenedioxy) phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-3-oxo-2H-1,4- benzothiazine((+)-III) were synthesized. Compounds (+)-I, (+)-II and (+)-III were identified with the fecal metabolites M-I, M-II and M-III, respectively. The calcium antagonistic activities of (+)-I, (+)-II and (+)-III were examined.

摘要

为了确定新型钙拮抗剂(+)-3,4-二氢-2-[5-甲氧基-2-[3-[N-甲基-N-[2-[(3,4-亚甲二氧基)苯氧基]乙基]氨基]丙氧基]苯基]-4-甲基-3-氧代-2H-1,4-苯并噻嗪(SD-3211)在大鼠体内三种粪便代谢物M-I、M-II和M-III的结构，合成了(+)-3,4-二氢-2-[5-羟基-2-[3-[N-甲基-N-[2-[(3,4-亚甲二氧基)苯氧基]乙基]氨基]丙氧基]苯基]-4-甲基-3-氧代-2H-1,4-苯并噻嗪((+)-I)、(+)-3,4-二氢-2-[5-羟基-2-[3-[N-[2-[(3,4-亚甲二氧基)苯氧基]乙基]氨基]丙氧基]苯基]-4-甲基-3-氧代-2H-1,4-苯并噻嗪((+)-II)和(+)-3,4-二氢-2-[5-甲氧基-2-[3-[N-[2-[(3,4-亚甲二氧基)苯氧基]乙基]氨基]丙氧基]苯基]-4-甲基-3-氧代-2H-1,4-苯并噻嗪((+)-III)。化合物(+)-I、(+)-II和(+)-III分别与粪便代谢物M-I、M-II和M-III进行了鉴定。检测了(+)-I、(+)-II和(+)-III的钙拮抗活性。