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Discovery of a lead series of potent benzodiazepine 5-HT2C receptor agonists with high selectivity in functional and binding assays.

Abstract：

:A series of potential new 5-HT2 receptor scaffolds based on a simplification of the clinically studied, 5-HT2CR agonist vabicaserin, were designed. An in vivo feeding assay early in our screening process played an instrumental part in the lead identification process, leading us to focus on a 6,5,7-tricyclic scaffold. A subsequent early SAR investigation provided potent agonists of the 5-HT2C receptor that were highly selective in both functional and binding assays, had good rat PK properties and that significantly reduced acute food intake in the rat.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Ren A,Zhu X,Feichtinger K,Lehman J,Kasem M,Schrader TO,Wong A,Dang H,Le M,Frazer J,Unett DJ,Grottick AJ,Whelan KT,Morgan ME,Sage CR,Semple G

doi

10.1016/j.bmcl.2019.126929

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

126929

issue

5

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(19)30912-6

journal_volume

30

pub_type

杂志文章

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