51865-85-1

Upstream product

• 73178-43-5 (E)-diethyl glutaconate 
• 1068-57-1 acetic acid hydrazide 
• 105-50-0 diethyl 1,3-acetonedicarboxylate 
• 2049-67-4 diethyl glutaconate 
• 73192-75-3 (Z)-diethyl pent-2-enedioate 
• 89479-76-5 3-hydroxyiminopentanedioic acid diethyl ester 
• 54889-50-8 diethyl 3-amino-2-pentene-1,5-dioate 
• 64-17-5 ethanol 
• 1948-48-7 3-aminopentanedioic acid 
• 119507-22-1 1,3-diethyl 2-benzylaminoglutarate 

Downstream Products

• 1117-23-3 3-aminopentane-1,5-diol 
• 1345984-09-9 diethyl 3-{[2-({[(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)-2-oxoethyl]amino}pentanedioate 
• 1345982-97-9 3-{[2-({[(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)-2-oxoethyl]amino}pentanedioic acid trifluoroacetate 
• 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 
• 1345982-69-5 3-({[(3R,5R)-3-butyl-3-ethyl-7-(methyloxy)-1,1-dioxo-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepin-8-yl]methyl}amino)pentanedioic acid 
• 1345983-96-1 diethyl 3-({3-[(3R,5R)-3-butyl-3-ethyl-7-(methyloxy)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepin-8-yl]propanoyl}amino)pentanedioate 
• 1345982-55-9 3-({3-[(3R,5R)-3-butyl-3-ethyl-7-(methyloxy)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepin-8-yl]propanoyl}amino)pentanedioic acid trifluoroacetate 
• 1948-48-7 3-aminopentanedioic acid 

Relevant academic research and scientific papers

CHEMICAL COMPOUNDS

The present disclosure describes novel compounds, or their pharmaceutically acceptable salts, pharmaceutical compositions containing them, and their medical uses. Compounds of the disclosure have activity as dual modulators of Janus kinase (JAK), alone, or in combination with one or more of an additional mechanism, including a tyrosine kinase, such as TrkA or Syk, and PDE4, and are useful in the in the treatment or control of inflammation, auto-immune diseases, cancer, and other disorders and indications where modulation of JAK would be desirable. Also described herein are methods of treating inflammation, auto-immune diseases, cancer, and other conditions susceptible to inhibition of JAK and PDE4 by administering a compound herein described.

NOVEL 5-AMINO-2-THIOIMIDAZOLE COMPOUNDS AND THEIR USE

The present invention is directed to novel compounds of formula (I) pharmaceutically acceptable salts or solvates thereof, and their use.

SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS

The present invention relates to novel substituted bridged urea compounds, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS

Provided herein are novel substituted bridged urea and related analogs and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

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.