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Development of indole sulfonamides as cannabinoid receptor negative allosteric modulators.

Abstract：

:Existing CB1 negative allosteric modulators (NAMs) fall into a limited range of structural classes. In spite of the theoretical potential of CB1 NAMs, published in vivo studies have generally not been able to demonstrate the expected therapeutically-relevant CB1-mediated effects. Thus, a greater range of molecular tools are required to allow definitive elucidation of the effects of CB1 allosteric modulation. In this study, we show a novel series of indole sulfonamides. Compounds 5e and 6c (ABD1075) had potencies of 4 and 3nM respectively, and showed good oral exposure and CNS penetration, making them highly versatile tools for investigating the therapeutic potential of allosteric modulation of the cannabinoid system.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Greig IR,Baillie GL,Abdelrahman M,Trembleau L,Ross RA

doi

10.1016/j.bmcl.2016.08.018

subject

Has Abstract

pub_date

2016-09-15 00:00:00

pages

4403-4407

issue

18

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(16)30839-3

journal_volume

26

pub_type

杂志文章

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