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Discovery of substituted lactams as novel dual orexin receptor antagonists. Synthesis, preliminary structure-activity relationship studies and efforts towards improved metabolic stability and pharmacokinetic properties. Part 1.

Abstract：

:Starting from a thiazolidin-4-one HTS hit, a novel series of substituted lactams was identified and developed as dual orexin receptor antagonists. In this Letter, we describe our initial efforts towards the improvement of potency and metabolic stability. These investigations delivered optimized lead compounds with CNS drug-like properties suitable for further optimization.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Sifferlen T,Boller A,Chardonneau A,Cottreel E,Hoecker J,Aissaoui H,Williams JT,Brotschi C,Heidmann B,Siegrist R,Gatfield J,Treiber A,Brisbare-Roch C,Jenck F,Boss C

doi

10.1016/j.bmcl.2013.12.092

subject

Has Abstract

pub_date

2014-02-15 00:00:00

pages

1201-8

issue

4

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)01476-5

journal_volume

24

pub_type

杂志文章

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