单胺氧化酶-A抑制剂盐酸四氢吲哚（S）-（+）-和（R）-（-）-异构体的拆分、EPC合成、绝对立体化学及药理学

Resolution, EPC-syntheses, absolute stereochemistry, and pharmacology of the (S)-(+)- and (R)-(-)-isomers of the MAO-A inhibitor tetrindole hydrochloride.

作者信息

Bös M, Canesso R, Kettler R, Keller H H, Schönholzer P

机构信息

Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd., Basel.

出版信息

Arch Pharm (Weinheim). 1995 Jul-Aug;328(7-8):619-22. doi: 10.1002/ardp.19953280710.

DOI:10.1002/ardp.19953280710

PMID:7492268

Abstract

Resolution of (RS)-tetrindole (3) and enantioselective reductions of the imine 7 yielded (S)-(+)-(4) and (R)-(-)-tetrindole (5). The absolute stereochemistry of 4 was established by X-ray analysis of the corresponding Mosher amide 6. From in vitro as well as in vivo data (MAO-inhibition, levels of monoamines and their respective metabolites in rat brain), 4 was identified as the eutomer.

摘要

（RS）-四氢吲哚（3）的拆分以及亚胺7的对映选择性还原得到了（S）-（+）-（4）和（R）-（-）-四氢吲哚（5）。通过对相应的莫舍尔酰胺6进行X射线分析确定了4的绝对立体化学结构。根据体外和体内数据（单胺氧化酶抑制、大鼠脑中单胺及其各自代谢物的水平），4被确定为优映体。