1456616-42-4

Usage

Uses

Used in Pharmaceutical Industry:
Tert-butyl ((2S,3R)-2-(2,5-difluorophenyl)-5-oxotetrahydro-2H-pyran-3-yl)carbamate is used as a therapeutic agent for the treatment of type 2 diabetes. Its application is based on its ability to inhibit the DPP-4 enzyme, which plays a crucial role in the regulation of glucose levels in the body. By inhibiting DPP-4, tert-butyl ((2S,3R)-2-(2,5-difluorophenyl)-5-oxotetrahydro-2H-pyran-3-yl)carbamate can help improve glycemic control and provide a potential treatment option for patients with type 2 diabetes.
Additionally, as an analog of Omarigliptin, it may also be used in the development of new drugs or therapies targeting DPP-4 for various medical conditions related to glucose metabolism and other potential applications in the pharmaceutical industry.

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 951127-26-7 1-(2,5-difluorophenyl)-2-nitroethanol 
• 2646-90-4 2,5-difluorobenzaldehyde 
• 951127-27-8 1-(2,5-difluorophenyl)-2-nitroethanone 
• 1456616-39-9 C₁₂H₁₁F₂NO₃ 
• 951127-28-9 6-(2,5-difluorophenyl)-3-methylidene-5-nitro-3,4-dihydro-2H-pyran 
• 35730-09-7 2,5-difluorobenzoyl chloride 

Downstream Products

• 1456616-64-0 C₁₆H₁₈F₂N₄O 
• 1456616-65-1 C₁₆H₁₈F₂N₄O 

Relevant academic research and scientific papers

A preparation method of the compounds

The invention discloses a preparation method of a compound. The preparation method comprises the steps: carrying out chemical resolution on a compound 3 namely 5-amino-6-(2,5-difluorophenyl)-tetrahydro-2H-pyran-3-ol, to obtain a salt formed from the compound 3 and a resolving agent; carrying out chemical combination of the salt formed from the compound 3 and the resolving agent with di-tert-butyl dicarbonate in an alkali liquid to obtain a compound 4; and oxidizing hydroxyl of the compound 4 to obtain a compound N-[(2R,3S)-2-(2,5-difluorophenyl)tetrahydro-5-oxo-2H-pyran-3-yl]-carbamic acid 1,1-dimethylethyl ester represented by the formula I. According to the preparation method, by selecting the low-price raw materials, the synthetic route is shortened, asymmetric hydrogenation reaction steps are omitted, and thus the production cost is greatly reduced, and the yield is significantly improved.

Omarigliptin (MK-3102): A novel long-acting DPP-4 inhibitor for once-weekly treatment of type 2 diabetes

In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected as a clinical development candidate. This manuscript summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for omarigliptin, which is currently in phase 3 clinical development.

Novel tetrahydropyran analogs as dipeptidyl peptidase IV inhibitors: Profile of clinical candidate (2R,3S,5R)-2-(2,5-difluorophenyl)-5-[2- (methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]tetrahydro-2H-pyran- 3-amine (23)

A series of novel tri-2,3,5-substituted tetrahydropyran analogs were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the series provided inhibitors with good DPP-4 potency and selectivity over other peptidases (QPP, DPP8, and FAP). Compound 23, which is very potent, selective, efficacious in the diabetes PD model, and has an excellent pharmacokinetic profile, is selected as a clinical candidate.