486459-98-7

Usage

Uses

Since Sitagliptin Defuoro IMpurity 4 is an impurity found in Sitagliptin, its primary use is in the context of pharmaceutical manufacturing and quality control. The applications of Sitagliptin Defuoro IMpurity 4 can be listed as follows:
Used in Pharmaceutical Manufacturing:
Sitagliptin Defuoro IMpurity 4 is used as a reference compound for monitoring and controlling the presence of impurities in the synthesis process of Sitagliptin. This helps ensure the purity and safety of the final drug product.
Used in Quality Control and Regulatory Compliance:
Sitagliptin Defuoro IMpurity 4 is used as a benchmark in quality control testing to verify that the levels of impurities in Sitagliptin are within acceptable limits, meeting regulatory standards and ensuring the quality of the medication.

Upstream product

• 848667-53-8 (R)-3-Amino-4-(2,5-difluoro-phenyl)-butyric acid methyl ester 
• 24424-99-5 di-tert-butyl dicarbonate 
• 767352-26-1 N-benzyloxy-4(R)-[1-methyl-(2,5-difluorobenzyl)]-2-oxoazetidine 
• 764667-66-5 5-[1-hydroxy-2-(2,5-difluorophenyl)ethylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 767352-25-0 N-benzyloxy-4-(2,5-difluorophenyl)-3(S)-hydroxybutanamide 
• 486460-02-0 (R,S)-N-(1,1-dimethylethoxycarbonyl)-2,5-difluorophenylalanine 
• 32133-38-3 2,5-difluoro-DL-phenylalanine 
• 486460-03-1 (R,S)-3-[(1,1-dimethylethoxycarbonyl)amino]-1-diazo-4-(2,5-difluoro-phenyl)butan-2-one 
• 837430-10-1 (2R,5S)-2,5-dihydro-3,6-dimethoxy-2-[(2',5'-difluorophenyl)methyl]-5-isopropylpyrazine 
• 837430-11-2 (R)-N-(1,1-dimethylethoxycarbonyl)-2,5-difluorophenylalanine methyl ester 
• 261380-31-8 (R)-N-(1,1-dimethylethoxycarbonyl)-2,5-difluorophenylalanine 
• 85117-99-3 2-(bromomethyl)-1,4-difluorobenzene 
• 85068-27-5 2,5-difluorophenylacetic acid 
• 767352-24-9 methyl 4-(2,5-difluorophenyl)-3-oxobutanoate 

Downstream Products

• 723286-62-2 ethyl 7-[(3R)-3-[(tert-butoxycarbonyl)amino]-4-(2,5-difluorophenyl)butanoyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carboxylate 
• 877402-36-3 tert-butyl-[(1R)-1-(2,5-difluorobenzyl)-3-hydrazino-3-oxopropyl]carbamate 

Relevant academic research and scientific papers

BETA-AMINO HETEROCYCLIC DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES

The present invention is directed to compounds which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) 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.

FUSED TRIAZOLE DERIVATIVES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES

The present invention is directed to novel fused triazole derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DPP-IV inhibitors") 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.

(2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a] pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: A potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes

A novel series of β-amino amides incorporating fused heterocycles, i.e., triazolopiperazines, were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H) -yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (1) is a potent, orally active DPP-IV inhibitor (IC50 = 18 nM) with excellent selectivity over other proline-selective peptidases, oral bioavailability in preclinical species, and in vivo efficacy in animal models. MK-0431, the phosphate salt of compound 1, was selected for development as a potential new treatment for type 2 diabetes.

Synthesis of a β-amino acid pharmacophore via a β-lactam intermediate

(Chemical Equation Presented) A stereoselective synthesis of (R)-β-amino acid 1 via a β-lactam intermediate is discussed.

PIPERIDINO PYRIMIDINE DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OF DIABETES

The present invention is directed to compounds which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DP-IV inhibitors") 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.

3-AMINO-4-PHENYLBUTANOIC ACID DERIVATIVES AS DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES

The present invention is directed to 3-amino-4-phenylbutanoic acid derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DP-IV inhibitors") 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.

Discovery of potent and selective β-homophenylalanine based dipeptidyl peptidase IV inhibitors

Modification of in-house screening lead β-aminoacyl proline 8 gave an equipotent thiazolidide 9. Extensive SAR studies on the phenyl ring of 9 led to the discovery of a novel series of potent and selective DP-IV inhibitors. Introduction of a fluorine at the 2-position proved to be crucial for the potency of this series. The 2,5-difluoro (22q) and 2,4,5-trifluoro (22t) analogues were potent inhibitors of DP-IV (IC50 = 270, 119 nM, respectively).

BETA-AMINO HETEROCYCLIC DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES

The present invention is directed to compounds which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DP-IV inhibitors") 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.