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Identification of an aminothiazole series of RORβ modulators.

Abstract：

:Crystallography has identified stearic acid, ALRT 1550 and ATRA as ligands that bind RORβ, however, none of these molecules represent good starting points to develop optimized small molecule modulators. Recently, Compound 1 was identified as a potent dual RORβ and RORγ inverse agonist with no activity towards RORα (Fig. 1). To our knowledge, this is one of only two small molecule RORβ inverse agonists identified in the primary literature from a tractable chemical series and represents an ideal starting point from which to design RORβ-selective modulators. Herein we describe our SAR optimization efforts that led to a series of potent neutral antagonists of RORβ.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Patouret R,Doebelin C,Garcia-Ordonez RD,Chang MR,Ruiz C,Cameron MD,Griffin PR,Kamenecka TM

doi

10.1016/j.bmcl.2018.03.001

subject

Has Abstract

pub_date

2018-04-15 00:00:00

pages

1178-1181

issue

7

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(18)30176-8

journal_volume

28

pub_type

杂志文章

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