18718-79-1Relevant articles and documents
Design and Structural Optimization of Dual FXR/PPARδActivators
Schierle, Simone,Neumann, Sebastian,Heitel, Pascal,Willems, Sabine,Kaiser, Astrid,Pollinger, Julius,Merk, Daniel
, p. 8369 - 8379 (2020/08/12)
Nonalcoholic steatohepatitis (NASH) is considered as severe hepatic manifestation of the metabolic syndrome and has alarming global prevalence. The ligand-activated transcription factors farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) δhave been validated as molecular targets to counter NASH. To achieve robust therapeutic efficacy in this multifactorial pathology, combined peripheral PPAR?-mediated activity and hepatic effects of FXR activation appear as a promising multitarget approach. We have designed a minimal dual FXR/PPARδactivator scaffold by rational fusion of pharmacophores derived from selective agonists. Our dual agonist lead compound exhibited weak agonism on FXR and PPARδand was structurally refined to a potent and balanced FXR/PPARδactivator in a computer-aided fashion. The resulting dual FXR/PPARδmodulator comprises high selectivity over related nuclear receptors and activates the two target transcription factors in native cellular settings.
Dimeric isoxazolyl-1,4-dihydropyridines have enhanced binding at the multi-drug resistance transporter
Steiger, Scott A.,Li, Chun,Backos, Donald S.,Reigan, Philip,Natale
supporting information, p. 3223 - 3234 (2017/05/29)
A series of dimeric isoxazolyl-1,4-dihydropyridines (IDHPs) were prepared by click chemistry and examined for their ability to bind the multi-drug resistance transporter (MDR-1), a member of the ATP-binding cassette superfamily (ABC). Eight compounds in t
Aromatic heterocyclic small molecule organic compounds and derivatives, preparation method and medical use
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Paragraph 0267-0268, (2016/11/17)
The invention discloses heterocyclic aromatic micromolecule organic compounds as shown in the structural formula (I) and derivatives thereof, or hydrates or pharmaceutically acceptable salts, and a preparation method of the corresponding compounds; the invention also discloses an application of the compounds and pharmaceutical compositions containing the compounds to the treatment of various metabolic syndrome-related diseases. The heterocyclic aromatic micromolecule organic compounds of the invention have excellent treatment effect on metabolic syndromes; experiment results show that the compounds may promote secretion of endogenous GLP-1, and are applicable to the preparation of anti-diabetic and fat-reducing candidate medicaments. Aiming at technical problems of easy degradation and short half life of current medicaments for treating diabetes, the invention provides novel, high-efficient micromolecule compounds for promoting secretion of endogenous GLP-1, and the compounds are applicable to the treatment of metabolic syndrome-related diseases such as diabetes, obesity and the like.