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Isoxazole-tethered diarylheptanoid analogs: Discovery of a new drug-like PAR2 antagonist.
- Source :
-
Bioorganic & Medicinal Chemistry Letters . Jul2018, Vol. 28 Issue 13, p2285-2288. 4p. - Publication Year :
- 2018
-
Abstract
- A new class of isoxazole-tethered diarylheptanoids having characteristic 1,3- syn -diol and 1,3- anti -diol chemophoric moieties, e.g. 4a – d and 5a – c respectively, have been designed and synthesized starting from d -glucose following a stereo-conserved general synthetic strategy. The isoxazole heterocycle was installed using our recently elaborated methodology deploying Magtrieve™ as a selective oxidizing agent. Two of these new analogs 4a and 5a exhibited significantly improved in vitro drug-like properties including solubility, metabolic stability, cell permeability and lack of nonspecific cytotoxicity when compared with curcumin-I. In a HEK293 cell-based intracellular calcium [Ca 2+ ] i release assay, 4a and 5a , when tested at 30 μM, inhibited the trypsin agonist induced protease-activated receptor-2 (PAR2) activity by 80% and 70% respectively. IC 50 of 4a (SB70) has been determined as 6 μM which is in the same range of current benchmarks for PAR2 antagonists. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 28
- Issue :
- 13
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 130225506
- Full Text :
- https://doi.org/10.1016/j.bmcl.2018.05.032