| Quinoline-based derivatives of pirinixic acid as dual PPAR alpha/gamma agonists. | |
| | |
MedLine Citation:
|
PMID: 17610302 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Pirinixic acid is known for its peroxisome proliferator-activated receptor (PPAR) agonistic action. In a recent publication, we have shown that aliphatic alpha-substitution of pirinixic acid enhances both PPARalpha and PPARgamma agonism. The goal of this study was to evaluate, whether the PPAR agonism of pirinixic acid may be also maintained in quinoline-based derivatives. The present study revealed that the mere substitution of the dimethyl aniline moiety of pirinixic acid by quinoline leads to a total loss of PPARalpha/gamma agonism, whereas concomitant alpha-substitution with n-butyl or n-hexyl groups restores and even enforces PPAR activation, leading to potent dual PPARalpha/gamma agonists. In the following we report the synthesis of quinoline-based derivatives of pirinixic acid, which in a Gal4-based luciferase-reporter gene assay proved to be potent dual PPARalpha/gamma agonists. Molecular docking of compound 4 with FlexX suggests a binding mode resembling to that of tesaglitazar. |
| | |
Authors:
|
Laura Popescu; Oliver Rau; Jark Böttcher; Yvonne Syha; Manfred Schubert-Zsilavecz |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Archiv der Pharmazie Volume: 340 ISSN: 0365-6233 ISO Abbreviation: Arch. Pharm. (Weinheim) Publication Date: 2007 Jul |
Date Detail:
|
Created Date: 2007-07-10 Completed Date: 2007-10-03 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0330167 Medline TA: Arch Pharm (Weinheim) Country: Germany |
Other Details:
|
Languages: eng Pagination: 367-71 Citation Subset: IM |
Affiliation:
|
Johann Wolfgang Goethe University Frankfurt, Institute of Pharmaceutical Chemistry/ZAFES, Frankfurt, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals COS Cells Cercopithecus aethiops Genes, Reporter Luciferases / genetics Models, Molecular PPAR alpha / agonists* PPAR gamma / agonists* Pyrimidines / chemical synthesis*, chemistry, pharmacology Quinolines / chemical synthesis*, chemistry, pharmacology |
| Chemical | |
Reg. No./Substance:
|
0/PPAR alpha; 0/PPAR gamma; 0/Pyrimidines; 0/Quinolines; 50892-23-4/pirinixic acid; EC 1.13.12.-/Luciferases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Synthesis and pharmacological investigation of 3-subsituted-amino-2-methylsulfanyl-5,6,7,8-tetrahydr...
Next Document: Synthesis of four natural prenylflavonoids and their estrogen-like activities.