Phenoxyacetic acids as PPARδ partial agonists: Synthesis, optimization, and in vivo efficacy

Karen A. Evans; Barry G. Shearer; David D. Wisnoski; Dongchuan Shi; Steven M. Sparks; Daniel D. Sternbach; Deborah A. Winegar; Andrew N. Billin; Christy Britt; James M. Way; Andrea H. Epperly; Lisa M. Leesnitzer; Raymond V. Merrihew; Robert X. Xu; Millard H. Lambert; Jian Jin

doi:10.1016/j.bmcl.2011.02.077

Phenoxyacetic acids as PPARδ partial agonists: Synthesis, optimization, and in vivo efficacy

Karen A. Evans
, Barry G. Shearer
, David D. Wisnoski
, Dongchuan Shi
, Steven M. Sparks
, Daniel D. Sternbach
, Deborah A. Winegar
, Andrew N. Billin
, Christy Britt
, James M. Way
, Andrea H. Epperly
, Lisa M. Leesnitzer
, Raymond V. Merrihew
, Robert X. Xu
, Millard H. Lambert
, Jian Jin

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

8 Scopus citations

Abstract

A series of phenoxyacetic acids as subtype selective and potent hPPARδ partial agonists is described. Many analogues were readily accessible via a single solution-phase synthetic route which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of two potent exemplars which were further evaluated in vivo. Details of the SAR, optimization, and in vivo efficacy of this series are presented herein.

Original language	English
Pages (from-to)	2345-2350
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2011.02.077
State	Published - 15 Apr 2011
Externally published	Yes

Keywords

PPARd
Partial agonist

Access to Document

10.1016/j.bmcl.2011.02.077

Cite this

Evans, K. A., Shearer, B. G., Wisnoski, D. D., Shi, D., Sparks, S. M., Sternbach, D. D., Winegar, D. A., Billin, A. N., Britt, C., Way, J. M., Epperly, A. H., Leesnitzer, L. M., Merrihew, R. V., Xu, R. X., Lambert, M. H., & Jin, J. (2011). Phenoxyacetic acids as PPARδ partial agonists: Synthesis, optimization, and in vivo efficacy. Bioorganic and Medicinal Chemistry Letters, 21(8), 2345-2350. https://doi.org/10.1016/j.bmcl.2011.02.077

@article{b46331217b754ccdaf7e35968e277e05,

title = "Phenoxyacetic acids as PPARδ partial agonists: Synthesis, optimization, and in vivo efficacy",

abstract = "A series of phenoxyacetic acids as subtype selective and potent hPPARδ partial agonists is described. Many analogues were readily accessible via a single solution-phase synthetic route which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of two potent exemplars which were further evaluated in vivo. Details of the SAR, optimization, and in vivo efficacy of this series are presented herein.",

keywords = "PPARd, Partial agonist",

author = "Evans, \{Karen A.\} and Shearer, \{Barry G.\} and Wisnoski, \{David D.\} and Dongchuan Shi and Sparks, \{Steven M.\} and Sternbach, \{Daniel D.\} and Winegar, \{Deborah A.\} and Billin, \{Andrew N.\} and Christy Britt and Way, \{James M.\} and Epperly, \{Andrea H.\} and Leesnitzer, \{Lisa M.\} and Merrihew, \{Raymond V.\} and Xu, \{Robert X.\} and Lambert, \{Millard H.\} and Jian Jin",

year = "2011",

month = apr,

day = "15",

doi = "10.1016/j.bmcl.2011.02.077",

language = "English",

volume = "21",

pages = "2345--2350",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd.",

number = "8",

}

Evans, KA, Shearer, BG, Wisnoski, DD, Shi, D, Sparks, SM, Sternbach, DD, Winegar, DA, Billin, AN, Britt, C, Way, JM, Epperly, AH, Leesnitzer, LM, Merrihew, RV, Xu, RX, Lambert, MH & Jin, J 2011, 'Phenoxyacetic acids as PPARδ partial agonists: Synthesis, optimization, and in vivo efficacy', Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 8, pp. 2345-2350. https://doi.org/10.1016/j.bmcl.2011.02.077

TY - JOUR

T1 - Phenoxyacetic acids as PPARδ partial agonists

T2 - Synthesis, optimization, and in vivo efficacy

AU - Evans, Karen A.

AU - Shearer, Barry G.

AU - Wisnoski, David D.

AU - Shi, Dongchuan

AU - Sparks, Steven M.

AU - Sternbach, Daniel D.

AU - Winegar, Deborah A.

AU - Billin, Andrew N.

AU - Britt, Christy

AU - Way, James M.

AU - Epperly, Andrea H.

AU - Leesnitzer, Lisa M.

AU - Merrihew, Raymond V.

AU - Xu, Robert X.

AU - Lambert, Millard H.

AU - Jin, Jian

PY - 2011/4/15

Y1 - 2011/4/15

N2 - A series of phenoxyacetic acids as subtype selective and potent hPPARδ partial agonists is described. Many analogues were readily accessible via a single solution-phase synthetic route which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of two potent exemplars which were further evaluated in vivo. Details of the SAR, optimization, and in vivo efficacy of this series are presented herein.

AB - A series of phenoxyacetic acids as subtype selective and potent hPPARδ partial agonists is described. Many analogues were readily accessible via a single solution-phase synthetic route which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of two potent exemplars which were further evaluated in vivo. Details of the SAR, optimization, and in vivo efficacy of this series are presented herein.

KW - PPARd

KW - Partial agonist

UR - https://www.scopus.com/pages/publications/79953278556

U2 - 10.1016/j.bmcl.2011.02.077

DO - 10.1016/j.bmcl.2011.02.077

M3 - Article

C2 - 21414782

AN - SCOPUS:79953278556

SN - 0960-894X

VL - 21

SP - 2345

EP - 2350

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 8

ER -

Phenoxyacetic acids as PPARδ partial agonists: Synthesis, optimization, and in vivo efficacy

Abstract

Keywords

Access to Document

Fingerprint

Cite this