130403-93-9

Upstream product

• 64-19-7 acetic acid 
• 100858-33-1 (3R)-3-hydroxy-pyrrolidine-1-carboxylic acid benzyl ester 
• 1972-28-7 diethylazodicarboxylate 
• 108-24-7 acetic anhydride 
• 100858-32-0 (S)-3-hydroxy-1-pyrrolidinecarboxylic acid phenylmethyl ester 
• 95656-88-5 benzyl 3-hydroxypyrrolidine-1-carboxylate 
• 501-53-1 benzyl chloroformate 
• 174621-88-6 (S)-3-(acetyloxy)-1-pyrrolidinecarboxylic acid, phenylmethyl ester 

Downstream Products

• 100858-32-0 (S)-3-hydroxy-1-pyrrolidinecarboxylic acid phenylmethyl ester 
• 130403-94-0 (S)-(pyrrolidin-3-yl) acetate 
• 163457-21-4 (R)-benzyl 3-fluoropyrrolidine-1-carboxylate 

Relevant academic research and scientific papers

PROTEIN KINASE INHIBITOR PRODRUGS

The present invention relates to ester and phosphate prodrugs of the protein kinase inhibitor N-(2-chloro-6-methylphenyl)-2-[[2-methyl-6-((S)-3-hydroxypyrrolidin-1- yl)pyrimidin4-yl]amino]thiazole-5-carboxarnide (compound X), stereoisomers, isomeric mixtures including racemic mixtures, and/or 4-deutero substituted derivatives thereof.

1,2,4-OXADIAZOLE DERIVATIVES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES

The present invention is directed to novel 1,2,4-oxadiazole 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.

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

The present invention is directed to novel cyclohexylalanine 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.

PHENYLALANINE DERIVATIVES AS DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES

The present invention is directed to phenylalanine 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.

Fluoropyrrolidine amides as dipeptidyl peptidase IV inhibitors

Amides derived from fluorinated pyrrolidines and 4-substituted cyclohexylglycine analogues have been prepared and evaluated as inhibitors of dipeptidyl dipeptidase IV (DP-IV). Analogues which incorporated (S)-3-fluoropyrrolidine showed good selectivity for DP-IV over quiescent cell proline dipeptidase (QPP). Compound 48 had good pharmacokinetic properties and was orally active in an oral glucose tolerance test in lean mice.

Lipase-catalyzed practical synthesis of (R)-1-benzyl-3-hydroxy-2,5-pyrrolidinedione and its related compounds

A practical method for preparing (R)-1-benzyl-3-hydroxy-2,5-pyrrolidinedione (1) was investigated by the use of the enzymatic hydrolysis of its acetate (2a). Among several hydrolases examined here, lipase PS from Pseudomonas cepacia gave the best result: In a mixed solvent (1:1 v/v) of dioxane and a phosphate buffer (pH 7), the hydrolysis took place smoothly with a high enantioselectivity (E > 3000). Several 3-alkanoyl derivatives of 1 were subjected to the lipase PS-catalyzed hydrolysis. The chain length of the alkanoyl does not noticeably influence the reaction rate or the enantioselectivity. In contrast, the hydrolysis of the 1-benzoyl derivative proceeded slowly with a low enantioselectivity (E = 19). The syntheses of optically active 3-hydroxypyrrolidines and 3-hydroxypiperidines were also achieved under the reaction conditions similar to the lipase PS-catalyzed hydrolysis of 2a.