75450-34-9 Usage
Uses
Used in Pharmaceutical Industry:
7-Chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one is used as a specific inhibitor of the mitochondrial Na+/Ca2+ exchanger for studying the role of normal mitochondrial calcium dynamics in sustaining dendritic spinogenesis and preventing sudden death in a Guinea pig model of heart failure.
Used in Cellular Studies:
7-Chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one is used as a mitochondrial sodium-calcium exchanger (mNCX) inhibitor to investigate the role of mitochondrial calcium dynamics in cellular processes. Adequate controls must be employed in cellular studies due to its inhibition of voltage-gated Ca2+ channels.
Biological Activity
Selective antagonist of the mitochondrial Na + -Ca 2+ exchanger (IC 50 = 0.4 μ M).
Biochem/physiol Actions
Specific inhibitor of mitochondrial Na+/Ca2+ exchange as well as sarcoplasmic reticulum calcium-stimulated ATPase and possibly other calcium channels.
References
1) Cox?et al.?(1993),?Selectivity of inhibition of Na(+)-Ca2+ exchange of heart mitochondria by benzothiazepine CGP-37157; J. Cardiovasc. Pharmacol.,?21?595
2) Namekata?et al. (2015),?Pharmacological discrimination of plasmalemmal and mitochondrial sodium-calcium exchanger in cardiomyocyte-derived H9c2 cells; Biol. Pharm. Bull,?38?147
3) Baron & Thayer (1997),?CGP37157 modulates mitochondrial Ca2+ homeostasis in cultured rat dorsal root ganglion neurons; Eur. J. Pharmacol.,?340?295
4) Liu?et al.?(2014),?Inhibiting mitochondrial Na+/Ca2+ exchange prevents sudden death in a guinea pig model of heart failure; Circ. Res.,?115?44
5) Nicolau?et al.?(2009),?Mitochondrial Na+/Ca2+-exchanger blocker CGP37157 protects against chromaffin cell death elicited by veratridine;?J. Pharmacol. Exp. Ther.,?330?844
6) Ruiz?et al. (2014),?CGP37157, an inhibitor of the mitochondrial Na+/Ca2+ exchanger, protects neurons from excitotoxicity by blocking voltage gated Ca2+ channels; Cell Death Dis.,?5?e1156
Check Digit Verification of cas no
The CAS Registry Mumber 75450-34-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,5,4,5 and 0 respectively; the second part has 2 digits, 3 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 75450-34:
(7*7)+(6*5)+(5*4)+(4*5)+(3*0)+(2*3)+(1*4)=129
129 % 10 = 9
So 75450-34-9 is a valid CAS Registry Number.
InChI:InChI=1/C15H11Cl2NOS/c16-9-5-6-13-11(7-9)15(20-8-14(19)18-13)10-3-1-2-4-12(10)17/h1-7,15H,8H2,(H,18,19)
75450-34-9Relevant academic research and scientific papers
Efficient syntheses of benzothiazepines as antagonists for the mitochondrial sodium-calcium exchanger: Potential therapeutics for type II diabetes
Pei, Yazhong,Lilly, Michael J.,Owen, David J.,D'Souza, Lawrence J.,Tang, Xiao-Qing,Yu, Jinghua,Nazarbaghi, Ramina,Hunter, Andrew,Anderson, Christen M.,Glasco, Susan,Ede, Nicholas J.,James, Ian W.,Maitra, Uday,Chandrasekaran,Moos, Walter H.,Ghosh, Soumitra S.
, p. 92 - 103 (2007/10/03)
Type II diabetes mellitus is a chronic metabolic disorder that can lead to serious cardiovascular, renal, neurologic, and retinal complications. While several drugs are currently prescribed to treat type II diabetes, their efficacy is limited by mechanism-related side effects (weight gain, hypoglycemia, gastrointestinal distress), inadequate efficacy for use as monotherapy, and the development of tolerance to the agents. Consequently, combination therapies are frequently employed to effectively regulate blood glucose levels. We have focused on the mitochondrial sodium-calcium exchanger (mNCE) as a novel target for diabetes drug discovery. We have proposed that inhibition of the mNCE can be used to regulate calcium flux across the mitochondrial membrane, thereby enhancing mitochondrial oxidative metabolism, which in turn enhances glucose-stimulated insulin secretion (GSIS) in the pancreatic β-cell. In this paper, we report the facile synthesis of benzothiazepines and derivatives by S-alkylation using 2-aminobenzhydrols. The syntheses of other bicyclic analogues based on benzothiazepine, benzothiazecine, benzodiazecine, and benzodiazepine templates are also described. These compounds have been evaluated for their inhibition of mNCE activity, and the results from the structure-activity relationship (SAR) studies are discussed.
