146062-49-9

Usage

Uses

CAY10415 is used to study blood glucose levels and rates of insulin-stimulated lipogenesis.

Biological Activity

msdc-0160 is a prototype mtot-modulating insulin sensitizer [1].msdc-0160 is a thiazolidinedione insulin sensitizer without the peroxisome proliferator–activated receptor-γ (ppar-γ)-dependent side effects. co-incubation of islets with msdc-0160 and igf-1 reduces the resistance of insulin-signaling pathway and preserves insulin content. msdc-0160 at 50μm alone also prevents the loss of insulin content significantly. besides that, treatment of msdc-0160 increases the phosphorylation of ampk and reduces mtor phosphorylation. moreover, msdc-0160 is also found to display pro-survival effects in human islets via reducing the level of cleaved caspase-3 and increasing the expression of apoptosis-related genes such as bcl2. in addition, msdc-0160 exerts prevention of nuclear translocation with β-catenin localized on the cell membrane or cytoplasm in human β-cells [1].

references

[1] rohatgi n, aly h, marshall c a, et al. novel insulin sensitizer modulates nutrient sensing pathways and maintains β-cell phenotype in human islets. plos one, 2013, 8(5): e62012.

Upstream product

• 101931-00-4 5-{4-[2-(5-ethyl-pyridin-2-yl)-2-hydroxyethoxy]benzyl}-2,4-thiazolidinedione 
• 471295-99-5 (5Z)-5-{4-[2-(5-ethylpyridin-2-yl)-2-hydroxyethoxy]benzylidene}-1,3-thiazolidine-2,4-dione 
• 67-68-5 dimethyl sulfoxide 
• 5408-74-2 5-ethyl-2-vinyl-pyridine 
• 768-61-6 2-hydroxymethyl-5-ethyl pyridine 
• 123-08-0 4-hydroxy-benzaldehyde 
• 103788-60-9 5-[(4-hydroxyphenyl)methylene]-2,4-thiazolidinedione 
• 1359827-43-2 2-bromo-1-(5-ethyl-2-pyridinyl)ethanone O-methyloxime 
• 74772-78-4 5-(4-hydroxybenzyl)-2,4-thiazolidinedione 
• 1359827-44-3 5-({4-[2-(5-ethyl-2-pyridinyl)-2-(methoxyimino)ethoxy]phenyl}methyl)-2,4-thiazolidinedione 
• 1359827-42-1 2-bromo-1-(5-ethylpyridin-2-yl)ethanone hydrobromide 
• 214701-49-2 1-(5-bromopyridin-2-yl)ethanone 
• 286411-85-6 1-(5-ethyl-2-pyridinyl)ethanone 
• 624-28-2 2,5-dibromopyridine 

Relevant academic research and scientific papers

The development of improved syntheses of PPARγ-sparing, insulin sensitizing thiazolidinedione-ketones

Ketones 2 (MSDC-0160) and 3 (MSDC-0602) had been selected for clinical development, however their initial syntheses were considered suboptimal for application deep into clinical trials. Difficulties ranging from the nature of the starting material, alcohol oxidation problems, epoxide opening regioisomeric issues, and endgame ketone redox problems had been encountered. Direct ketone introduction/maintenance was desired for maximum efficiency and convergence was found to be critically dependent upon the acidity of the nucleophilic species (13, 18) and the use of pre- or post-alkylative oximino-ether/oxime protection (vide infra). Improvements in overall yield for the syntheses of 2 (MSDC-0160) and 3 (MSDC-0602) from 20% (2) and 31% (3) respectively, to 44% (2) and 59% (3) were realized.

5-DEUTERO-2,4-THIAZOLIDINEDIONE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

The invention provides 5-deuterium-enriched 2,4-thiazolidinediones (e.g., 5-[4-[2-(5-ethyl-2-pyridyl)-2-oxoethoxy]benzyl]-5-deutero-thiazolidine-2,4-dione), deuterated derivatives thereof, stereoisomers thereof, pharmaceutically acceptable salt forms thereof, and methods of treatment using the same.

SYNTHESIS FOR THIAZOLIDINEDIONE COMPOUNDS

The present invention provides novel methods for synthesizing PPARgamma sparing compounds, e.g., thiazolidinediones, that are useful for preventing and/or treating metabolic disorders such as diabetes, obesity, hypertension, and inflammatory diseases.

POLYMORPHS OF 5-(4-(2-(5-ETHYLPYRIDIN-2-YL)-2-OXOETHOXY)BENZYL)-1,3-THIAZOLIDINE-2,4-DIONE (MITOGLITAZONE)

The present invention relates to novel polymorphs of 5-(4-(2-(5-ethylpyridin-2-yl)-2-oxoethoxy) benzyl)-l,3-thiazolidine-2,4-dione of formula (I) and processes for the preparation thereof and pharmaceutical compositions comprising the novel crystalline po

Process development and scale-up of the potential thiazolidinedione antidiabetic candidate PNU-91325

An efficient six-step synthesis has been developed for the preparation of the thiazolidinedione analogue PNU-91325 (3) from the commercially available olefin 12. This process involves a novel epoxide ring opening with a deactivated phenol under phase-transfer conditions. Significant improvements were made in the oxidation of a secondary alcohol to the ketone and the 1,4-reduction of an enone from a previous process. Overall, this route allows for the preparation of PNU-91325 in 25% yield.

Synthesis and biological activity of metabolites of the antidiabetic, antihyperglycemic agent pioglitazone

Pioglitazone (5-(4-(2-(5-ethyl-2-pyridyl)ethoxy)benzyl)-2,4- thiazolidinedione, 2) is a prototypical antidiabetic thiazolidinedione that had been evaluated for possible clinical development. Metabolites 6-9 have been identified after dosing of rats and dogs. Ketone 10 has not yet been identified as a metabolite but has been added to the list as a putative metabolite by analogy to alcohol 6 and ketone 7. We have developed improved syntheses of pioglitazone (2) metabolites 6-9 and the putative metabolite ketone 10. These entities have been compared in the KKA(y) mouse model of human type-II diabetes to pioglitazone (2). Ketone 10 has proven to be the most potent of these thiazolidinediones in this in vivo assay. When 6-10 were compared in vitro in the 3T3-L1 cell line to 2, for their ability to augment insulin-stimulated lipogenesis, 10 was again the most potent compound with 6, 7, and 9 roughly equivalent to 2. These data suggest that metabolites 6, 7, and 9 are likely to contribute to the pharmacological activity of pioglitazone (2), as had been previously reported for ciglitazone (1).

Thiazolidinedione derivatives, production and use thereof

A thiazolidinedione compound of the formula STR1 wherein X,Q are as defined in the specification. The compounds are used for treating diabetes.