Design and structural analysis of novel pharmacophores for potent and selective peroxisome proliferator-activated receptor γ agonists

Chia Hui Lin; Yi Hui Peng; Mohane Selvaraj Coumar; Santhosh Kumar Chittimalla; Chun Chen Liao; Ping Chiang Lyn; Chin Chieh Huang; Tzu Wen Lien; Wen Hsing Lin; John T.A. Hsu; Jai Hong Cheng; Xin Chen; Jian Sung Wu; Yu Sheng Chao; Hwei Jen Lee; Chiun Gung Juo; Su Ying Wu; Hsing Pang Hsieh

doi:10.1021/jm801594x

Design and structural analysis of novel pharmacophores for potent and selective peroxisome proliferator-activated receptor γ agonists

Chia Hui Lin
, Yi Hui Peng
, Mohane Selvaraj Coumar
, Santhosh Kumar Chittimalla
, Chun Chen Liao
, Ping Chiang Lyn
, Chin Chieh Huang
, Tzu Wen Lien
, Wen Hsing Lin
, John T.A. Hsu
, Jai Hong Cheng
, Xin Chen
, Jian Sung Wu
, Yu Sheng Chao
, Hwei Jen Lee
, Chiun Gung Juo
, Su Ying Wu
, Hsing Pang Hsieh

Center of Applied Nanomedicine

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

21 Citations (Scopus)

Abstract

Utilizing medicinal chemistry design strategies such as benzo splitting and ring expansion, we converted PPARα/γ dual agonist 1 to selective PPARα agonists 19 and 20. Compounds 19 and 20 were 2- to 4-fold better than rosiglitazone at PPARγ receptor, with 80- to 100-fold PPARγ selectivity over PPARα receptor. X-ray cocrystal studies in PPARγ and modeling studies in PPARα give molecular insights for the improved PPARγ potency and selectivity for 19 when compared to 1.

Original language	English
Pages (from-to)	2618-2622
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	52
Issue number	8
DOIs	https://doi.org/10.1021/jm801594x
Publication status	Published - 2009 Apr 23

All Science Journal Classification (ASJC) codes

Molecular Medicine
Drug Discovery

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10.1021/jm801594x

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Lin, C. H., Peng, Y. H., Coumar, M. S., Chittimalla, S. K., Liao, C. C., Lyn, P. C., Huang, C. C., Lien, T. W., Lin, W. H., Hsu, J. T. A., Cheng, J. H., Chen, X., Wu, J. S., Chao, Y. S., Lee, H. J., Juo, C. G., Wu, S. Y., & Hsieh, H. P. (2009). Design and structural analysis of novel pharmacophores for potent and selective peroxisome proliferator-activated receptor γ agonists. Journal of Medicinal Chemistry, 52(8), 2618-2622. https://doi.org/10.1021/jm801594x

@article{c526de5d5614402b846e895f63603fc3,

title = "Design and structural analysis of novel pharmacophores for potent and selective peroxisome proliferator-activated receptor γ agonists",

abstract = "Utilizing medicinal chemistry design strategies such as benzo splitting and ring expansion, we converted PPARα/γ dual agonist 1 to selective PPARα agonists 19 and 20. Compounds 19 and 20 were 2- to 4-fold better than rosiglitazone at PPARγ receptor, with 80- to 100-fold PPARγ selectivity over PPARα receptor. X-ray cocrystal studies in PPARγ and modeling studies in PPARα give molecular insights for the improved PPARγ potency and selectivity for 19 when compared to 1.",

author = "Lin, \{Chia Hui\} and Peng, \{Yi Hui\} and Coumar, \{Mohane Selvaraj\} and Chittimalla, \{Santhosh Kumar\} and Liao, \{Chun Chen\} and Lyn, \{Ping Chiang\} and Huang, \{Chin Chieh\} and Lien, \{Tzu Wen\} and Lin, \{Wen Hsing\} and Hsu, \{John T.A.\} and Cheng, \{Jai Hong\} and Xin Chen and Wu, \{Jian Sung\} and Chao, \{Yu Sheng\} and Lee, \{Hwei Jen\} and Juo, \{Chiun Gung\} and Wu, \{Su Ying\} and Hsieh, \{Hsing Pang\}",

year = "2009",

month = apr,

day = "23",

doi = "10.1021/jm801594x",

language = "English",

volume = "52",

pages = "2618--2622",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

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Lin, CH, Peng, YH, Coumar, MS, Chittimalla, SK, Liao, CC, Lyn, PC, Huang, CC, Lien, TW, Lin, WH, Hsu, JTA, Cheng, JH, Chen, X, Wu, JS, Chao, YS, Lee, HJ, Juo, CG, Wu, SY & Hsieh, HP 2009, 'Design and structural analysis of novel pharmacophores for potent and selective peroxisome proliferator-activated receptor γ agonists', Journal of Medicinal Chemistry, vol. 52, no. 8, pp. 2618-2622. https://doi.org/10.1021/jm801594x

TY - JOUR

T1 - Design and structural analysis of novel pharmacophores for potent and selective peroxisome proliferator-activated receptor γ agonists

AU - Lin, Chia Hui

AU - Peng, Yi Hui

AU - Coumar, Mohane Selvaraj

AU - Chittimalla, Santhosh Kumar

AU - Liao, Chun Chen

AU - Lyn, Ping Chiang

AU - Huang, Chin Chieh

AU - Lien, Tzu Wen

AU - Lin, Wen Hsing

AU - Hsu, John T.A.

AU - Cheng, Jai Hong

AU - Chen, Xin

AU - Wu, Jian Sung

AU - Chao, Yu Sheng

AU - Lee, Hwei Jen

AU - Juo, Chiun Gung

AU - Wu, Su Ying

AU - Hsieh, Hsing Pang

PY - 2009/4/23

Y1 - 2009/4/23

N2 - Utilizing medicinal chemistry design strategies such as benzo splitting and ring expansion, we converted PPARα/γ dual agonist 1 to selective PPARα agonists 19 and 20. Compounds 19 and 20 were 2- to 4-fold better than rosiglitazone at PPARγ receptor, with 80- to 100-fold PPARγ selectivity over PPARα receptor. X-ray cocrystal studies in PPARγ and modeling studies in PPARα give molecular insights for the improved PPARγ potency and selectivity for 19 when compared to 1.

AB - Utilizing medicinal chemistry design strategies such as benzo splitting and ring expansion, we converted PPARα/γ dual agonist 1 to selective PPARα agonists 19 and 20. Compounds 19 and 20 were 2- to 4-fold better than rosiglitazone at PPARγ receptor, with 80- to 100-fold PPARγ selectivity over PPARα receptor. X-ray cocrystal studies in PPARγ and modeling studies in PPARα give molecular insights for the improved PPARγ potency and selectivity for 19 when compared to 1.

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U2 - 10.1021/jm801594x

DO - 10.1021/jm801594x

M3 - Article

C2 - 19301897

AN - SCOPUS:65249083580

SN - 0022-2623

VL - 52

SP - 2618

EP - 2622

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 8

ER -

Design and structural analysis of novel pharmacophores for potent and selective peroxisome proliferator-activated receptor γ agonists

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