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Pyrazole[3,4-e][1,4]thiazepin-7-one derivatives as a novel class of Farnesoid X Receptor (FXR) agonists
- Source :
-
Bioorganic & Medicinal Chemistry . Jun2012, Vol. 20 Issue 11, p3429-3445. 17p. - Publication Year :
- 2012
-
Abstract
- Abstract: A virtual screening procedure was applied to the discovery of structurally diverse non-steroidal Farnesoid X Receptor (FXR) agonists. From 117 compounds selected by virtual screening, a total of 47 compounds were found to be FXR agonists, with 34 of them showing activity below a concentration of 20μM. 1H-Pyrazole[3,4-e][1,4]thiazepin-7-one-based hit compound 7 was chosen for hit-to-lead optimization. A large number of 1H-pyrazole[3,4-e][1,4]thiazepin-7-one derivatives was designed, synthesized, and evaluated by a cell-based luciferase transactivation assay for their agonistic activity against FXR. Most of them exhibited low micromolar range of potency and very high efficacy. [Copyright &y& Elsevier]
- Subjects :
- *PYRAZOLES
*FARNESOID X receptor
*LUCIFERASES
*AZOLES
*ANTIPYRINE
*BENZOSELENADIAZOLE
Subjects
Details
- Language :
- English
- ISSN :
- 09680896
- Volume :
- 20
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 75192994
- Full Text :
- https://doi.org/10.1016/j.bmc.2012.04.021