486460-08-6

Upstream product

• 1213132-66-1 methyl (R)-2-amino-3-(2,4,5-trifluorophenyl)propanoate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 486460-07-5 (2S,5R)-2,5-dihydro-3,6-dimethoxy-2-isopropyl-5-(2',4',5'-trifluorobenzyl)-pyrazine 
• 1500076-05-0 (Z)-methyl 2-((tert-butoxycarbonyl)amino)-3-(2,4,5-trifluorophenyl)acrylate 
• 165047-24-5 2,4,5-trifluorobenzaldehyde 
• 121056-95-9 trimethyl 2-(tert-butoxycarbonylamino)phosphonoacetate 
• 157911-56-3 2,4,5-trifluorobenzyl bromide 

Downstream Products

• 1246220-99-4 (R)-tert-butyl (1-hydroxy-3-(2,4,5-trifluorophenyl)propan-2-yl)carbamate 
• 1500076-26-5 (R)-1-(5-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-3-(2,4,5-trifluorophenyl)propan-2-amine hydrochloride 
• 1500076-25-4 (R)-(1-(2-amino-3-(2,4,5-trifluorophenyl)propyl)-1H-1,2,3-triazol-5-yl)methanol hydrochloride 
• 1500076-24-3 (R)-1-(5-phenyl-1H-1,2,3-triazol-1-yl)-3-(2,4,5-trifluorophenyl)propan-2-amine hydrochloride 
• 1500076-23-2 (R)-1-(4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-3-(2,4,5-trifluorophenyl)propan-2-amine hydrochloride 
• 1500076-22-1 (R)-(1-(2-amino-3-(2,4,5-trifluorophenyl)propyl)-1H-1,2,3-triazol-4-yl)methanol hydrochloride 
• 1500076-21-0 (R)-1-(4-phenyl-1H-1,2,3-triazol-1-yl)-3-(2,4,5-trifluorophenyl)propan-2-amine hydrochloride 
• 1500076-12-9 (R)-tert-butyl (1-(5-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-3-(2,4,5-trifluorophenyl)propan-2-yl)carbamate 
• 1500076-11-8 (R)-tert-butyl (1-(5-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)-3-(2,4,5-trifluorophenyl)propan-2-yl)carbamate 
• 1500076-10-7 (R)-tert-butyl (1-(5-phenyl-1H-1,2,3-triazol-1-yl)-3-(2,4,5-trifluorophenyl)propan-2-yl)carbamate 
• 1500076-09-4 (R)-tert-butyl (1-(4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-3-(2,4,5-trifluorophenyl)propan-2-yl)carbamate 
• 1500076-08-3 (R)-tert-butyl (1-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)-3-(2,4,5-trifluorophenyl)propan-2-yl)carbamate 
• 1500076-07-2 (R)-tert-butyl (1-(4-phenyl-1H-1,2,3-triazol-1-yl)-3-(2,4,5-trifluorophenyl)propan-2-yl)carbamate 
• 1246221-01-1 C₁₅H₂₀F₃NO₅S 

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.

Design and synthesis of 4-(2,4,5-Trifluorophenyl)butane-1,3-diamines as dipeptidyl peptidase IV inhibitors

The worldwide prevalence of diabetes has spurred numerous studies on the development of new antidiabetic medicines. As a result, dipeptidyl peptidaseIV (DPP4) has been recognized as a validated target. In our efforts to discover new DPP4 inhibitors, we analyzed the complexed structures of DPP4 available in Protein Data Bank and designed a series of triazole compounds. After enzyme activity assays and crystallographic verification of the binding interaction patterns, we found that the triazole compounds can inhibit DPP4 with micromolar IC50 values. Liver microsome stability and cytochrome P450 metabolic tests were performed on this series, revealing undesirable pharmacokinetic profiles for the triazole compounds. To overcome this liability, we substituted the triazole ring with an amide or urea group to produce a new series of DPP4 inhibitors. Based on its enzyme activity, metabolic stability, and selectivity over DPP8 and DPP9, we selected compound 21r for further study of its invivo effects in mice using an oral glucose tolerance test (OGTT). The results show that 21r has efficacy similar to that of sitagliptin at a dose of 3mgkg-1. The crystal structure of 21r bound to DPP4 also reveals that the trifluoromethyl group is directed toward a subpocket different from the subsite bound by sitagliptin, providing clues for the design of new DPP4 inhibitors.

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.

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.

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.