SYNTHESIS AND BIOLOGICAL-ACTIVITY OF 3-[2-(DIMETHYLAMINO)ETHYL]-5-[(1,1-DIOXO-5-METHYL-1,2,5-THIADIAZOLIDIN-2-YL)-METHYL]-1H-INDOLE AND ANALOGS - AGONISTS FOR THE 5-HT1D RECEPTOR

被引：53

作者：

CASTRO, JL

BAKER, R

GUIBLIN, AR

HOBBS, SC

JENKINS, MR

RUSSELL, MGN

BEER, MS

STANTON, JA

SCHOLEY, K

HARGREAVES, RJ

GRAHAM, MI

MATASSA, VG

机构：

[1] MERCK SHARP & DOHME LTD, NEUROSCI RES CTR, DEPT BIOCHEM, RES LABS, HARLOW CM20 2QR, ESSEX, ENGLAND

[2] MERCK SHARP & DOHME LTD, NEUROSCI RES CTR, DEPT PHARMACOL, RES LABS, HARLOW CM20 2QR, ESSEX, ENGLAND

[3] MERCK SHARP & DOHME LTD, RES LABS, DEV LABS, HODDESDON EN11 9BU, HERTS, ENGLAND

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1994年 / 37卷 / 19期

关键词：

D O I：

10.1021/jm00045a006

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of 5-(1,1-dioxo-1,2,5-thiadiazolidin-2-yl)tryptamines was designed, synthesized, and evaluated as 5-HT1D receptor agonists. Compounds such as 8d,f,k were identified which had comparable affinity, potency, and receptor selectivity to that of the antimigraine drug sumatriptan. Both 8d,k were found to be well absorbed in the rat with oral bioavailabilities of 66% and 62%, respectively. Additionally, 8d was found to be selective over other non-serotonergic receptors and exhibited relatively low central nervous system penetration.

引用

页码：3023 / 3032

页数：10

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