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Design, synthesis, and analysis of antagonists of GPR55: Piperidine-substituted 1,3,4-oxadiazol-2-ones.

Abstract：

:A series of 1,3,4-oxadiazol-2-ones was synthesized and tested for activity as antagonists at GPR55 in cellular beta-arrestin redistribution assays. The synthesis was designed to be modular in nature so that a sufficient number of analogues could be rapidly accessed to explore initial structure-activity relationships. The design of analogues was guided by the docking of potential compounds into a model of the inactive form of GPR55. The results of the assays were used to learn more about the binding pocket of GPR55. With this oxadiazolone scaffold, it was determined that modification of the aryl group adjacent to the oxadiazolone ring was often detrimental and that the distal cyclopropane was beneficial for activity. These results will guide further exploration of this receptor.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Meza-Aviña ME,Lingerfelt MA,Console-Bram LM,Gamage TF,Sharir H,Gettys KE,Hurst DP,Kotsikorou E,Shore DM,Caron MG,Rao N,Barak LS,Abood ME,Reggio PH,Croatt MP

doi

10.1016/j.bmcl.2016.02.030

subject

Has Abstract

pub_date

2016-04-01 00:00:00

pages

1827-1830

issue

7

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(16)30142-1

journal_volume

26

pub_type

杂志文章

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