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Usage

Uses

Used in Pharmaceutical Industry:
GSK 2330672 is used as a therapeutic agent for the treatment of diabetes and related metabolic disorders. It functions by inhibiting the apical sodium-dependent bile acid transporter (ASBT), which leads to increased fecal bile acid secretion, reduced hemoglobin A1c (HbA1c) and plasma glucose levels, and increased total GLP-1 and plasma insulin in diabetic rats. This makes it a promising candidate for the development of new treatments for diabetes and other metabolic conditions.

Upstream product

• 613-70-7 2-methoxyphenyl acetate 
• 69845-06-3 3-hydroxy-4-methoxythiophenol 
• 51865-85-1 1,3-diethyl 2-aminoglutarate 
• 1345983-46-1 (3R,5R)-3-butyl-3-ethyl-7-(methyloxy)-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepine-8-carbaldehyde 1,1-dioxide 
• 77313-09-8 3-aminoglutaric acid dimethyl ester 
• 1948-48-7 3-aminopentanedioic acid 
• 1345983-39-2 (3R,5R)-3-butyl-3-ethyl-7-methoxy-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[f][1,4]thiazepin-8-yl trifluoromethanesulfonate 
• 1345983-43-8 (3R,5R)-3-butyl-3-ethyl-7-(methyloxy)-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepine-8-carbonitrile-1,1-dioxide 
• 1345984-00-0 diethyl 3-({[(3R,5R)-3-butyl-3-ethyl-7-(methyloxy)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepin-8-yl]methyl}amino)pentanedioate 
• 1345983-90-5 dimethyl 3-({[(3R,5R)-3-butyl-3-ethyl-7-(methyloxy)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepin-8-yl]methyl}amino)pentanedioate 
• 1345983-89-2 dimethyl 3-aminopentanedioate acetate 

Relevant academic research and scientific papers

SYNTHESIS OF BENZOTHIAZEPINES

Methods for preparing the following compound are disclosed.

Discovery of a highly potent, nonabsorbable apical sodium-dependent bile acid transporter inhibitor (GSK2330672) for treatment of type 2 diabetes

The apical sodium-dependent bile acid transporter (ASBT) transports bile salts from the lumen of the gastrointestinal (GI) tract to the liver via the portal vein. Multiple pharmaceutical companies have exploited the physiological link between ASBT and hepatic cholesterol metabolism, which led to the clinical investigation of ASBT inhibitors as lipid-lowering agents. While modest lipid effects were demonstrated, the potential utility of ASBT inhibitors for treatment of type 2 diabetes has been relatively unexplored. We initiated a lead optimization effort that focused on the identification of a potent, nonabsorbable ASBT inhibitor starting from the first-generation inhibitor 264W94 (1). Extensive SAR studies culminated in the discovery of GSK2330672 (56) as a highly potent, nonabsorbable ASBT inhibitor which lowers glucose in an animal model of type 2 diabetes and shows excellent developability properties for evaluating the potential therapeutic utility of a nonabsorbable ASBT inhibitor for treatment of patients with type 2 diabetes.

CHEMICAL COMPOUNDS

Compounds of Formula (I) and methods for treating metabolic disorders are disclosed.