- Asymmetric synthesis of the four diastereoisomers of a novel non-steroidal farnesoid X receptor (FXR) agonist: Role of the chirality on the biological activity
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An asymmetric synthetic strategy was designed for the preparation of the four possible diastereoisomers of 3,6-dimethyl-1-(2-methylphenyl)-4-(4- phenoxyphenyl)-4,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-one, a non-steroidal FXR agonist, we recently discovered following a virtual screening approach. The results obtained from an AlphaScreen assay clearly demonstrated that only the isomer endowed with 4R,6S absolute configuration is responsible for the biological activity. A deep investigation of the different putative binding modes adopted by these enantiomerically pure ligands using computational modeling studies confirmed the enantioselectivity of FXR towards this class of molecules.
- Marinozzi, Maura,Carotti, Andrea,Sardella, Roccaldo,Buonerba, Federica,Ianni, Federica,Natalini, Benedetto,Passeri, Daniela,Rizzo, Giovanni,Pellicciari, Roberto
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p. 3780 - 3789
(2013/07/19)
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- Identification and optimization of substituted 5-aminopyrazoles as potent and selective adenosine A1 receptor antagonists
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Potent and selective adenosine A1 receptor antagonists were disclosed. SAR and pharmacological profile of selected compounds were discussed.
- Griebenow, Nils,B?rfacker, Lars,Meier, Heinrich,Schneider, Dirk,Teusch, Nicole,Lustig, Klemens,Kast, Raimund,Kolkhof, Peter
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scheme or table
p. 5891 - 5894
(2010/11/18)
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