1361050-75-0

Upstream product

• 67-56-1 methanol 
• 1246960-25-7 (R)-3-(((benzyloxy)carbonyl)amino)-4-(2,4,5-trifluorophenyl)butanoic acid 
• 769195-26-8 4-(2,4,5-trifluoro-phenyl)-3-oxo-butyric acid methyl ester 
• 501-53-1 benzyl chloroformate 
• 1361050-65-8 (E)-1-benzyl-4-methyl-2-(2,4,5-trifluorobenzylidene)succinate 
• 1361050-70-5 (R)-4-methoxy-4-oxo-2-(2,4,5-trifluorobenzyl)butanoic acid 
• 100-51-6 benzyl alcohol 

Downstream Products

• 1246960-25-7 (R)-3-(((benzyloxy)carbonyl)amino)-4-(2,4,5-trifluorophenyl)butanoic acid 

Relevant academic research and scientific papers

Synthesis, in vitro evaluation, and computational simulations studies of 1,2,3-triazole analogues as DPP-4 inhibitors

Novel 1,2,3-triazole analogues (S7 ~ S10) were synthesized and evaluated for their inhibitory activity against hDPP-4. All the 1,2,3-triazole analogues exhibited moderate in vitro hDPP-4 inhibitory activities (265 ~ 780 nM). These results are somewhat less potent compared to those of known 1,2,3-triazole analogues (S1 ~ S6, 14 ~ 254 nM). S2 and S3 manifested excellent potency against hDPP-4 with IC50s of 28 and 14 nM, respectively. The role of the 1,2,3-triazole moiety in binding the molecule to the target was investigated using combined 10 1,2,3-triazole analogues (S1 ~ S10). Molecular dynamics (MD) simulations following the aforementioned docking phase were performed to elucidate potential binding modes of sitagliptin's 1,2,3-triazole analogues in hDPP-4, with the use of a cocrystal structure of hDPP-4 with sitagliptin (PDB ID: 1X70). Docking and MD simulations of the complexes of hDPP-4 with sitagliptin, S2 and S3 suggest that Glu205, Glu206, Tyr662, and Tyr666 would be the key amino acid residues for the binding of the molecules with the receptor. Especially, S2 and S3 showed additional strong π-π interaction between Phe357 and 1,2,3-triazole. Same strong π-π interaction is also observed between Phe357 and the 1,2,4-triazole ring of sitagliptin. Furthermore, additional interactions with Tyr547, Cys551, and especially Arg358 would enhance the binding affinity of the compounds for the pocket of the enzyme. In overall, in vitro hDPP-4 inhibitory activities of synthetic 1,2,3-triazole analogues were well matched with results of computational simulations studies.

Glucovance west Geleg sandbank intermediate process for the preparation of amino acid derivatives

The invention discloses a preparation method of a new diabetes drug sitagliptin intermediate aminobenzene butyric acid derivative. The preparation method comprises the following steps of: (1) mixing a compound shown in a formula I with R(+)-alpha-phenethyl and acetic acid to obtain a compound shown in a formula II; (2) mixing the compound shown in the formula II with sodium borohydride and protonic acid or lewis acid to obtain a compound shown in a formula III; (3) mixing the compound shown in the formula III with X to obtain a compound shown in a formula IV; (4) mixing the compound as shown in the formula IV with an inorganic base 1 to obtain a compound shown in a formula V; (5) obtaining a compound shown in a formula VI by the compound shown in the formula V; and (6) mixing the compound shown in the formula VI with an inorganic base 2 to obtain a compound shown in a formula VII.

Process for the production of sitagliptin

The present invention is directed to a process for the preparation of Sitagliptin, having formula (I)