Design, synthesis, and evaluation of a new class of noncyclic 1,3-dicarbonyl compounds as PPARα selective activators

Zhibin Li, Chenzhong Liao, Chi Bun Ko, Song Shan, Edith H.Y. Tong, Zihui Yin, Desi Pan, Vincent K.W. Wong, Leming Shi, Zhi Qiang Ning, Weiming Hu, Jiaju Zhou, Stephen S.M. Chung, Xian Ping Lu

Research output: Journal article publicationJournal articleAcademic researchpeer-review

20 Citations (Scopus)

Abstract

Lipid accumulation in nonadipose tissues is increasingly linked to the development of type 2 diabetes in obese individuals. We report here the design, synthesis, and evaluation of a series of novel PPARα selective activators containing 1,3-dicarbonyl moieties. Structure-activity relationship studies led to the identification of PPARα selective activators (compounds 10, 14, 17, 18, and 21) with stronger potency and efficacy to activate PPARα over PPARγ and PPARδ. Experiments in vivo showed that compounds 10, 14, and 17 had blood glucose lowering effect in diabetic db/db mouse model after two weeks oral dosing. The data strongly support further testing of these lead compounds in other relevant disease animal models to evaluate their potential therapeutic benefits.
Original languageEnglish
Pages (from-to)3507-3511
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume14
Issue number13
DOIs
Publication statusPublished - 5 Jul 2004
Externally publishedYes

Keywords

  • Metabolic diseases
  • Noncyclic 1,3-dicarbonyl compounds
  • PPARα activators
  • Type 2 diabetes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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