6IZM

Crystal structure of the PPARgamma-LBD complexed with compound 1l

Summary for 6IZM

• Entry DOI: 10.2210/pdb6izm/pdb
• Descriptor: Peroxisome proliferator-activated receptor gamma, Peptide from Peroxisome proliferator-activated receptor gamma coactivator 1-alpha, 3-[[6-(2,6-dimethylpyridin-3-yl)oxy-1-methyl-benzimidazol-2-yl]methoxy]benzoic acid, ... (4 entities in total)
• Functional Keywords: transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 34883.39

Authors

Matsui, Y.,Hanzawa, H. (deposition date: 2018-12-20, release date: 2019-03-27, Last modification date: 2023-11-22)

Primary citation

Shinozuka, T.,Tsukada, T.,Fujii, K.,Tokumaru, E.,Matsui, Y.,Wakimoto, S.,Ogata, T.,Araki, K.,Sawamura, R.,Watanabe, N.,Mori, M.,Tanaka, J.
Structure-Activity Relationship Studies of 3- or 4-Pyridine Derivatives of DS-6930.
Acs Med.Chem.Lett., 10:358-362, 2019

PubMed Abstract: Derivatization efforts were continued to discover backups for a potent selective PPARγ modulator, DS-6930. In this Letter, the replacement of 2-pyridine ring in DS-6930 with 3- or 4-pyridyl group is reported. As the introduction of substituents on the pyridine ring did not provide potent partial agonists, modifications of benzimidazole ring were explored to discover potent intermediate agonists. 4'-Alkoxy substituted benzimidazoles failed to show potent efficacy in vivo, whereas 7'-fluoro benzimidazole (DS19161384) was found to result in robust plasma glucose reductions with excellent DMPK profiles.

PubMed: 30891140
DOI: 10.1021/acsmedchemlett.8b00645

Experimental method

X-RAY DIFFRACTION (1.8 Å)