Synthesis and structure-activity relationships of a series of 3-aryl-4-isoxazolecarboxamides as a new class of TGR5 agonists

Brian W. Budzik; Karen A. Evans; David D. Wisnoski; Jian Jin; Ralph A. Rivero; George R. Szewczyk; Channa Jayawickreme; David L. Moncol; Hongshi Yu

doi:10.1016/j.bmcl.2010.01.003

Synthesis and structure-activity relationships of a series of 3-aryl-4-isoxazolecarboxamides as a new class of TGR5 agonists

Brian W. Budzik, Karen A. Evans, David D. Wisnoski, Jian Jin, Ralph A. Rivero, George R. Szewczyk, Channa Jayawickreme, David L. Moncol, Hongshi Yu

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

Abstract

A series of 3-aryl-4-isoxazolecarboxamides identified from a high-throughput screening campaign as novel, potent agonists of the human TGR5 G-protein-coupled receptor is described. Many analogues were readily accessible via solution-phase synthesis which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of potent exemplars (up to pEC₅₀ = 9). Details of the SAR and optimization of this series are presented herein.

Original language	English
Pages (from-to)	1363-1367
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	4
DOIs	https://doi.org/10.1016/j.bmcl.2010.01.003
State	Published - 15 Feb 2010
Externally published	Yes

Keywords

GPCR
SAR
Solution-phase synthesis
TGR5
TGR5 agonists

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title = "Synthesis and structure-activity relationships of a series of 3-aryl-4-isoxazolecarboxamides as a new class of TGR5 agonists",

abstract = "A series of 3-aryl-4-isoxazolecarboxamides identified from a high-throughput screening campaign as novel, potent agonists of the human TGR5 G-protein-coupled receptor is described. Many analogues were readily accessible via solution-phase synthesis which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of potent exemplars (up to pEC50 = 9). Details of the SAR and optimization of this series are presented herein.",

keywords = "GPCR, SAR, Solution-phase synthesis, TGR5, TGR5 agonists",

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AU - Budzik, Brian W.

AU - Evans, Karen A.

AU - Wisnoski, David D.

AU - Jin, Jian

AU - Rivero, Ralph A.

AU - Szewczyk, George R.

AU - Jayawickreme, Channa

AU - Moncol, David L.

AU - Yu, Hongshi

PY - 2010/2/15

Y1 - 2010/2/15

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AB - A series of 3-aryl-4-isoxazolecarboxamides identified from a high-throughput screening campaign as novel, potent agonists of the human TGR5 G-protein-coupled receptor is described. Many analogues were readily accessible via solution-phase synthesis which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of potent exemplars (up to pEC50 = 9). Details of the SAR and optimization of this series are presented herein.

KW - GPCR

KW - SAR

KW - Solution-phase synthesis

KW - TGR5

KW - TGR5 agonists

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SN - 0960-894X

VL - 20

SP - 1363

EP - 1367

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 4

ER -

Synthesis and structure-activity relationships of a series of 3-aryl-4-isoxazolecarboxamides as a new class of TGR5 agonists

Abstract

Keywords

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