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Synthesis and Biological Assessment of 4,1-Benzothiazepines with Neuroprotective Activity on the Ca 2+ Overload for the Treatment of Neurodegenerative Diseases and Stroke.
- Source :
-
Molecules . Aug2021, Vol. 26 Issue 15, p4473-4473. 1p. - Publication Year :
- 2021
-
Abstract
- In excitable cells, mitochondria play a key role in the regulation of the cytosolic Ca2+ levels. A dysregulation of the mitochondrial Ca2+ buffering machinery derives in serious pathologies, where neurodegenerative diseases highlight. Since the mitochondrial Na+/Ca2+ exchanger (NCLX) is the principal efflux pathway of Ca2+ to the cytosol, drugs capable of blocking NCLX have been proposed to act as neuroprotectants in neuronal damage scenarios exacerbated by Ca2+ overload. In our search of optimized NCLX blockers with augmented drug-likeness, we herein describe the synthesis and pharmacological characterization of new benzothiazepines analogues to the first-in-class NCLX blocker CGP37157 and its further derivative ITH12575, synthesized by our research group. As a result, we found two new compounds with an increased neuroprotective activity, neuronal Ca2+ regulatory activity and improved drug-likeness and pharmacokinetic properties, such as clog p or brain permeability, measured by PAMPA experiments. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 26
- Issue :
- 15
- Database :
- Academic Search Index
- Journal :
- Molecules
- Publication Type :
- Academic Journal
- Accession number :
- 151786783
- Full Text :
- https://doi.org/10.3390/molecules26154473