146062-49-9

Basic information

• Product Name: CAY10415
• Synonyms: CAY10415;2,4-Thiazolidinedione, 5-[[4-[2-(5-ethyl-2-pyridinyl)-2-oxoethoxy]phenyl]methyl]-;CAY10415 (Mitoglitazone);Mitoglitazone;5-[[4-[2-(5-ethyl-2-pyridinyl)-2-oxoethoxy]phenyl]methyl]-2,4-Thiazolidinedione;5-(4-(2-(5-Ethylpyridin-2-yl)-2-oxoethoxy)-benzyl)thiazolidine-2,4-dione;MSDC-0160(CAY10415)
• CAS NO: 146062-49-9
• Molecular Formula: C19H18N2O4S
• Molecular Weight: 370.43
• Product Categories: Inhibitors
• Mol File: 146062-49-9.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 623.8±55.0 °C(Predicted)
• Appearance: /
• Density: 1.315±0.06 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility: ≥37 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O
• PKA: 6.32±0.50(Predicted)
• CAS DataBase Reference: CAY10415(CAS DataBase Reference)
• NIST Chemistry Reference: CAY10415(146062-49-9)
• EPA Substance Registry System: CAY10415(146062-49-9)

Safety Data

• Hazardous Substances Data: 146062-49-9(Hazardous Substances Data)

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 
• 105355-27-9 Pioglitazone 
• 145350-09-0 rac-2-(2-{4-[(2,4-dioxothiazolidin-5-yl)methyl]phenoxy}ethyl)-5-ethylpyridine-1-oxide 
• 624-28-2 2,5-dibromopyridine 
• 286411-85-6 1-(5-ethyl-2-pyridinyl)ethanone 
• 214701-49-2 1-(5-bromopyridin-2-yl)ethanone 
• 1359827-42-1 2-bromo-1-(5-ethylpyridin-2-yl)ethanone hydrobromide 
• 1359827-44-3 5-({4-[2-(5-ethyl-2-pyridinyl)-2-(methoxyimino)ethoxy]phenyl}methyl)-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 

Relevant articles and documents

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.

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.

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.