186392-40-5

Usage

Uses

Used in Pharmaceutical Industry:
CP 91149 is used as an inhibitor for glycogen phosphorylase, which plays a crucial role in regulating glucose metabolism. Its inhibition can lead to growth inhibition and has potential applications in the treatment of diabetes and other glycogen metabolism-related disorders.
Used in Anticancer Applications:
CP 91149 is used as an antitumor agent, particularly effective against A549 non-small cell lung carcinoma (NSCLC) cells that express endogenous brain GP. It inhibits glycogen accumulation and proliferation in these cells, making it a promising candidate for cancer treatment.
Used in Diabetes Treatment:
In vivo studies have shown that CP 91149 can lower plasma glucose levels in diabetic ob/ob mice without causing hypoglycemia, making it a potential therapeutic agent for the treatment of diabetes.

Biochem/physiol Actions

CP-91149 is a selective glycogen phosphorylase inhibitor.

in vitro

cp-91149 treatment suppressed glycogenolysis stimulated by glucagon in in primary human hepatocytes and isolated rat hepatocytes with ic50 value of 2.1 μm and 10–100 μm, respectively 1. inhibition of phosphorylase a by cp-91149 resulted in activation of glycogen synthase and translocation of the protein from a soluble to a particulate fraction, which mimicked the insulin- stimulated glycogen synthesis 2.

in vivo

treatment of cp-91149 on diabetic ob/ob mice at a dosage of 25–50 mg/kg was shown to lead to a rapid glucose lowering but did not change glucose levels in normoglycemic, nondiabetic mice 1.

references

1. martin wh, hoover dj, armento sj, et al. discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo. proceedings of the national academy of sciences of the united states of america. 1998;95(4):1776-1781.2. aiston s, coghlan mp, agius l. inactivation of phosphorylase is a major component of the mechanism by which insulin stimulates hepatic glycogen synthesis. european journal of biochemistry / febs. 2003;270(13):2773-2781.

InChI:InChI=1S/C21H22ClN3O3/c1-25(2)21(28)19(26)17(10-13-6-4-3-5-7-13)24-20(27)18-12-14-11-15(22)8-9-16(14)23-18/h3-9,11-12,17,19,23,26H,10H2,1-2H3,(H,24,27)/t17-,19+/m0/s1

Upstream product

• 186392-22-3 (2R,3S)-3-[(5-Chloro-1H-indole-2-carbonyl)-amino]-2-hydroxy-4-phenyl-butyric acid methyl ester 
• 139163-87-4 (2R,3S)-methyl 3-amino-2-hydroxy-4-phenylbutanoate 
• 105116-40-3 3(S),2(R)-N-[(1,1-dimethylethoxy)carbonyl]-3-amino-2-hydroxy-4-phenylbutyronitrile 
• 506-59-2 N,N-dimethylammonium chloride 
• 186392-32-5 (2R,3S)-3-[(5-Chloro-1H-indole-2-carbonyl)-amino]-2-hydroxy-4-phenyl-butyric acid 
• 186393-17-9 (2S,3S)-3-[(5-Chloro-1H-indole-2-carbonyl)-amino]-2-hydroxy-4-phenyl-butyric acid methyl ester 
• 62023-62-5 allophenylnorstatine 
• 10517-21-2 5-chloro-1H-Indole-2-carboxylic acid 
• 186393-16-8 (2S,3S)-3-[(5-Chloro-1H-indole-2-carbonyl)-amino]-2-hydroxy-4-phenyl-butyric acid 
• 186393-19-1 (2R,3R)-3-[(5-Chloro-1H-indole-2-carbonyl)-amino]-2-hydroxy-4-phenyl-butyric acid methyl ester 
• 62023-61-4 (2S,3R)-3-amino-2-hydroxy-4-phenylbutyric acid 
• 186392-36-9 (2R,3R)-3-[(5-Chloro-1H-indole-2-carbonyl)-amino]-2-hydroxy-4-phenyl-butyric acid 
• 59554-14-2 (2S,3R)-3-amino-2-hydroxy-4-phenylbutanoic acid 

Relevant academic research and scientific papers

Use of glycogen phosphorylase inhibitors

The invention provides methods of treating prophylactically an individual in whom Type 2 diabetes mellitus has not yet presented, but in whom there is an increased risk of developing such condition, which methods comprise administering to an individual in need thereof an effective amount of a glycogen phosphorylase inhibitor; effective amounts of a glycogen phosphorylase inhibitor and a non-glycogen phosphorylase inhibiting anti-diabetic agent; or effective amounts of a glycogen phosphorylase inhibitor and an anti-obesity agent. The invention further provides methods of treating prophylactically an individual in whom Type 2 diabetes mellitus has not yet presented, but in whom there is an increased risk of developing such condition, which methods comprise administering to an individual in need thereof a pharmaceutical composition comprising effective amounts of a glycogen phosphorylase inhibitor and a non-glycogen phosphorylase inhibiting anti-diabetic agent; or effective amounts of a glycogen phosphorylase inhibitor and an anti-obesity agent.

Tetrazole compounds as thyroid receptor ligands

The present invention relates to tetrazole compounds of Formula I, stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, and pharmaceutically acceptable salts of the prodrugs. The invention also relates to compositions comprising the tetrazole compounds and to methods of treating obesity, diabetes, atherosclerosis, hypertension, coronary heart disease, hypercholesterolemia, hyperlipidemia, thyroid disease, thyroid cancer, hypothyroidism, depression, glaucoma, cardiac arrhythmias, congestive heart failure, and osteoporosis using the tetrazole compounds.

Processes and intermediates for preparing 3(S)-[(5-chloro-1H-indole-2-carbonyl)-amino]-2(R)-hydroxy-4-phenyl-butyric acid

The present invention provides novel processes for preparing 3(S)-[(5-chloro-1H-indole-2-carbonyl)-amino]-2(R)-hydroxy-4-phenyl-butyric acid. Also provided are novel intermediates used in those processes. Further, the 3(S)-[(5-chloro-1H-indole-2-carbonyl)-amino]-2(R)-hydroxy-4-phenyl-butyric acid prepared by the novel processes can be further reacted to yield known indole 2-carboxamides and derivatives thereof possessing glycogen phosphorylase inhibitory activity, which are useful in the treatment of mammals, especially human beings, having glycogen phosphorylase dependent diseases or conditions.

Methods of treating diabetic cardiomyopathy using glycogen phosphorylase inhibitors

The present invention provides methods of treating diabetic cardiomyopathy, the methods comprising administering to a patient having or at risk of having diabetic cardiomyopathy a therapeutically effective amount of a glycogen phosphorylase inhibitor. The

Pharmaceutical compositions of glycogen phosphorylase inhibitors

Pharmaceutical compositions comprise a glycogen phosphorylase inhibitor and at least one concentration-enhancing polymer. The composition may be a simple physical mixture of glycogen phosphorylase inhibitor and concentration-enhancing polymer or a dispersion of glycogen phosphorylase inhibitor and polymer.

Substituted n-(indole-2-carbonyl-) amides and derivatives as glycogen phosphorylase inhibitors

Compounds of the formula I: and their compositions are useful as glycogen phosphorylase inhibitors.

COMBINATION OF AN ALDOSE REDUCTASE INHIBITOR AND A GLYCOGEN PHOSPHORYLASE INHIBITOR

Pharmaceutical combination compositions and methods including aldose reductase inhibitors and glycogen phosphorylase inhibitors. The compositions and methods are useful for the treatment insulin resistant conditions such as diabetes and in reducing tissue

Method of reducing tissue damage associated with non-cardiac ischemia using glycogen phosphorylase inhibitors

A method of preventing non-cardiac tissue damage resulting from ischemia and/or hypoxia, comprising administering to a patient in need of such treatment an effective amount of an glycogen phosphorylase inhibitor.

Use of glycogen phosphorylase inhibitor for reducing non-cardiac tissue damage resulting from ischemia

The use of a glycogen phosphorylase inhibitor for the manufacture of a medicament for reducing non-cardiac tissue damage resulting from ischemia or hypoxia.