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Identification of potent, nonabsorbable agonists of the calcium-sensing receptor for GI-specific administration.

Abstract：

:Modulation of gastrointestinal nutrient sensing pathways provides a promising a new approach for the treatment of metabolic diseases including diabetes and obesity. The calcium-sensing receptor has been identified as a key receptor involved in mineral and amino acid nutrient sensing and thus is an attractive target for modulation in the intestine. Herein we describe the optimization of gastrointestinally restricted calcium-sensing receptor agonists starting from a 3-aminopyrrolidine-containing template leading to the identification of GI-restricted agonist 19 (GSK3004774).

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Sparks SM,Spearing PK,Diaz CJ,Cowan DJ,Jayawickreme C,Chen G,Rimele TJ,Generaux C,Harston LT,Roller SG

doi

10.1016/j.bmcl.2017.09.008

subject

Has Abstract

pub_date

2017-10-15 00:00:00

pages

4673-4677

issue

20

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(17)30896-X

journal_volume

27

pub_type

杂志文章

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