951127-28-9

Usage

Uses

Used in Pharmaceutical Industry:
6-(2,5-difluorophenyl)-3-methylidene-5-nitro-3,4-dihydro-2H-pyran is used as a key intermediate in the synthesis of pyrrolo[3,4]pyrozole derivatives. These derivatives have potential therapeutic applications, particularly in the treatment of DPP-IV related diseases. DPP-IV, also known as dipeptidyl peptidase-4, is an enzyme involved in the regulation of glucose levels in the body. Inhibition of this enzyme can lead to improved glucose control and has been a target for the development of drugs to treat type 2 diabetes and other metabolic disorders.

Upstream product

• 35730-09-7 2,5-difluorobenzoyl chloride 
• 951127-26-7 1-(2,5-difluorophenyl)-2-nitroethanol 
• 2646-90-4 2,5-difluorobenzaldehyde 
• 951127-27-8 1-(2,5-difluorophenyl)-2-nitroethanone 
• 17616-43-2 3-iodo-2-(iodomethyl)-1-propene 

Downstream Products

• 1226781-87-8 tert-butyl {(2R,3S,5R)-2-(2,5-difluorophenyl)-5-[2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]tetrahydro-2H-pyran-3-yl}carbamate 
• 1226781-44-7 Omarigliptin 
• 1601479-76-8 (2R,3 S,5R)-2-(2,5-difluorophenyl)-5-(tetrahydro-1H-furo[3,4-c]pyrrol-5(3H)-yl)tetrahydro-2H-pyran-3-amine 
• 1601482-72-7 tert-butyl ((2R,3S,5R)-2-(2,5-difluorophenyl)-5-(tetrahydro-1H-furo[3,4-c]pyrrol-5(3H)-yl)tetrahydro-2H-pyran-3-yl)carbamate 
• 1601479-75-7 (2R,3S,5R)-2-(2,5-difluorophenyl)-5-(7-(methylsulfonyl)-2,7-diazaspiro[4.4]nonan-2-yl)tetrahydro-2H-pyran-3-amine 
• 1601482-71-6 tert-butyl ((2R,3S,5R)-2-(2,5-difluorophenyl)-5-(7-(methylsulfonyl)-2,7-diazaspiro[4.4]nonan-2-yl)tetrahydro-2H-pyran-3-yl)carbamate 
• 1601479-72-4 (2R,3S,5R)-2-(2,5-difluorophenyl)-5-(5-(methylsulfonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)tetrahydro-2H-pyran-3-amine 
• 1601482-70-5 tert-butyl ((2R,3S,5R)-2-(2,5-difluorophenyl)-5-(5-(methylsulfonyl)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)tetrahydro-2H-pyran-3-yl)carbamate 

Relevant academic research and scientific papers

Amino tetrahydropyrane derivatives

The invention provides amino tetrahydropyrane derivatives, pharmaceutically-acceptable salts, hydrates, solvates, stereoisomers and prodrugs of the amino tetrahydropyrane derivatives, a preparation method of the amino tetrahydropyrane derivatives and a pharmaceutical composition containing the compounds. A formula (I) of the amino tetrahydropyrane derivatives is as shown in the specification. The compounds are capable of inhibiting activity of DPP-IV (dipeptidyl peptidase IV) and can be used for treating dipeptidyl peptidase IV associated diseases such as diabetes, obesity and other metabolic diseases.

AMINOTETRAHYDROPYRAN DERIVATIVE USED AS DIPEPTIDYL PEPTIDASE-IV INHIBITOR

Provided is an Aminotetrahydropyran derivative represented by general formula (I), a preparation method for the derivative, a pharmaceutical composition containing the derivative, and the use of the derivative to prepare a therapeutic agent, especially a dipeptidyl peptidase-IV inhibitor.

Inhibitor for dipeptidyl peptidase-IV

The invention provides an aminotetrahydropyran derivative with a general formula (I) as described in the specification, pharmaceutically acceptable salts, hydrates, solvates and stereoisomers thereof, a preparation method for the aminotetrahydropyran derivative, and a pharmaceutical composition containing the aminotetrahydropyran derivative. The aminotetrahydropyran derivative provided by the invention can inhibit the activity of dipeptidyl peptidase-IV(DPP-IV), and can be used for treatment of diseases related to dipeptidyl peptidase-IV, especially for treatment of diabetes.

Aminotetrahydropyrane derivatives and medical applications thereof

The invention discloses aminotetrahydropyrane derivatives and medical applications thereof. The invention relates to substituted aminotetrahydropyrane with a novel structural formula (I). The substituted aminotetrahydropyrane can be used as an inhibitor of dipeptidyl peptidase-IV, and can be applied to treatment or prevention of diseases related with dipeptidyl peptidase-IV, such as diabetes, especially type II diabetes. The invention also relates to a pharmaceutical composition comprising the aminotetrahydropyrane derivatives, and an application of the compounds and the composition in the treatment or prevention of diseases related with dipeptidyl peptidase-IV.

2-PHENYL-5-HETEROCYCLYL-TETRAHYDRO-2H-PYRAN-3-AMINE COMPOUNDS FOR USE IN THE TREATMENT OF DIABETES AND ITS ASSOCIATED DISORDERS

The present invention relates to novel compounds of the general formula (I) their tautomeric forms, their enantiomers, their diastereoisomers, their pharmaceutically accepted salts, or pro-drugs thereof, which are useful for the treatment or prevention of diabetes mellitus (DM), obesity and other metabolic disorders. The invention also relates to process for the manufacture of said compounds, and pharmaceutical compositions containing them and their use.

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.

AMINOTETRAHYDROPYRANS AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES

The present invention is directed to novel substituted aminotetrahydropyrans of structural formula I which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

AMINOTETRAHYDROPYRANS AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES

The present invention is directed to novel substituted aminotetrahydropyrans of structural formula I which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved

NOVEL CRYSTALLINE FORM OF A DIHYDROCHLORIDE SALT OF A DIPEPTIDYL PEPTIDASE-IV INHIBITOR

The present invention relates to a novel crystalline form of the dihydrochloride salt of (2R,3S,5S)-2-(2,5-difluorophenyl)-5-(4,6-dihydropyrrolo[3,4-c]pyrazol-5(1H)-yl)tetrahydro-2H-pyran-3-amine as well as a process for its preparation, pharmaceutical compositions containing this novel form, and methods of use of the novel form and pharmaceutical compositions for the treatment of Type 2 diabetes, hyperglycemia, insulin resistance, obesity, and high blood pressure.