1612191-86-2Relevant academic research and scientific papers
METHOD FOR THE SYNTHESIS OF A CHOLANE DERIVATIVE
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, (2021/10/30)
The present invention refers to a method for the preparation of a compound of formula (I).
Compound for treating metabolic diseases as well as preparation method and application thereof
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, (2019/07/04)
The invention provides a compound for treating metabolic diseases, the compound has a structure represented by formula (I) or formula (II), or a racemate, a stereoisomer, a geometric isomer, a tautomer, a solvate, a hydrate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. The compounds provided by the invention are FXR and/or TGR5 receptor activators, and the compounds havethe activity of activating FXR and/or TGR5 receptors, and can be used for preparing medicines for treating chronic liver diseases, metabolic diseases or portal hypertension.
CHOLANE DERIVATIVES FOR USE IN THE TREATMENT AND/OR PREVENTION OF FXR AND TGR5/GPBAR1 MEDIATED DISEASES
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Page/Page column 28-29, (2015/12/17)
13073PTWO 56 ABSTRACT The present invention relates to compounds having cholane scaffolds of formula (I), said compounds for use in the treatment and/or prevention of FXR and TGR5/GPBAR1 mediated diseases. 5
Exploitation of cholane scaffold for the discovery of potent and selective farnesoid X receptor (FXR) and G-protein coupled bile acid receptor 1 (GP-BAR1) ligands
Festa, Carmen,Renga, Barbara,D'Amore, Claudio,Sepe, Valentina,Finamore, Claudia,De Marino, Simona,Carino, Adriana,Cipriani, Sabrina,Monti, Maria Chiara,Zampella, Angela,Fiorucci, Stefano
, p. 8477 - 8495 (2015/01/09)
Nuclear and G-protein coupled receptors are considered major targets for drug discovery. FXR and GP-BAR1, two bile acid-activated receptors, have gained increasing consideration as druggable receptors. Because endogenous bile acids often target both receptor families, the development of selective ligands has been proven difficult, exposing patients to side effects linked to an unwanted activation of one of the two receptors. In the present study, we describe a novel library of semisynthetic bile acid derivatives obtained by modifications on the cholane scaffold. The pharmacological characterization of this library led to the discovery of 7α-hydroxy-5β-cholan-24-sulfate (7), 6β-ethyl-3α,7β-dihydroxy-5β-cholan-24-ol (EUDCOH, 26), and 6α-ethyl-3α, 7α-dihydroxy-24-nor-5β-cholan-23-ol (NorECDCOH, 30) as novel ligands for FXR and GP-BAR1 that might hold utility in the treatment of FXR and GP-BAR1 mediated disorders.
Design, synthesis, and biological evaluation of potent dual agonists of nuclear and membrane bile acid receptors
D'Amore, Claudio,Di Leva, Francesco Saverio,Sepe, Valentina,Renga, Barbara,Del Gaudio, Chiara,D'Auria, Maria Valeria,Zampella, Angela,Fiorucci, Stefano,Limongelli, Vittorio
, p. 937 - 954 (2014/03/21)
Bile acids exert genomic and nongenomic effects by interacting with membrane G-protein-coupled receptors, including the bile acid receptor GP-BAR1, and nuclear receptors, such as the farnesoid X receptor (FXR). These receptors regulate overlapping metabolic functions; thus, GP-BAR1/FXR dual agonists, by enhancing the biological response, represent an innovative strategy for the treatment of enteroendocrine disorders. Here, we report the design, total synthesis, and in vitro/in vivo pharmacological evaluation of a new generation of dual bile acid receptor agonists, with the most potent compound, 19, showing promising pharmacological profiles. We show that compound 19 activates GP-BAR1, FXR, and FXR regulated genes in the liver, increases the intracellular concentration of cAMP, and stimulates the release of the potent insulinotropic hormone GLP-1, resulting in a promising drug candidate for the treatment of metabolic disorders. We also elucidate the binding mode of the most potent dual agonists in the two receptors through a series of computations providing the molecular basis for dual GP-BAR1/FXR agonism.
