484664-62-2Relevant academic research and scientific papers
Enantioselective biotransformations of racemic and meso pyrrolidine-2,5-dicarboxamides and their application in organic synthesis
Chen, Peng,Gao, Ming,Wang, De-Xian,Zhao, Liang,Wang, Mei-Xiang
body text, p. 4063 - 4072 (2012/06/18)
In this paper, we report the amidase-catalyzed hydrolysis of pyrrolidine-2,5-dicarboxamides and their application in organic synthesis. Catalyzed by Rhodococcus erythropolis AJ270, an amidase containing microbial whole cell catalyst, racemic trans-pyrrolidine-2,5-carboxamide was kinetically resolved into (2S,5S)-pyrrolidine-2,5-dicarboxamide and (2R,5R)-5- carbamoylpyrrolidine-2-carboxylic acid in high yields and excellent enantioselectivity. Biocatalytic desymmetrization of meso cis- pyrrolidinedicarboxamide afforded enantiomerically pure (2R,5S)-5- carbamoylpyrrolidine-2-carboxylic acid in an almost quantitative yield. In both kinetic resolution and desymmetrization, the amidase always exhibited excellent 2R-enantioselectivity, although its catalytic efficiency was influenced dramatically by the steric effect of the substituent on the nitrogen atom of pyrrolidine ring. The synthetic potential of biotransformation was demonstrated by the scalable preparation of (2R,5R)- and (2R,5S)-5-carbamoylpyrrolidine-2- carboxylic acids and their conversions to aza-nucleoside analogues and druglike pyrroline-fused diazepin-11(5H)-one compounds.
cis-2,5-dicyanopyrrolidine inhibitors of dipeptidyl peptidase IV: Synthesis and in vitro, in vivo, and x-ray crystallographic characterization
Wright, Stephen W.,Ammirati, Mark J.,Andrews, Kim M.,Brodeur, Anne M.,Danley, Dennis E.,Doran, Shawn D.,Lillquist, Jay S.,McClure, Lester D.,McPherson, R. Kirk,Orena, Stephen J.,Parker, Janice C.,Polivkova, Jana,Qiu, Xiayang,Soeller, Walter C.,Soglia, Carolyn B.,Treadway, Judith L.,VanVolkenburg, Maria A.,Wang, Hong,Wilder, Donald C.,Olson, Thanh V.
, p. 3068 - 3076 (2007/10/03)
Inhibitors of the glucagon-like peptide-1 (GLP-1) degrading enzyme dipeptidyl peptidase IV (DPP-IV) have been shown to be effective treatments for type 2 diabetes in animal models and in human subjects. A novel series of cis-2,5-dicyanopyrrolidine α-amino amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. 1-({[1-(Hydroxymethyl)cyclopentyl]amino}-acetyl)pyrrolidine-2,5-cis- dicarbonitrile (1c) is an achiral, slow-binding (time-dependent) inhibitor of DPP-IV that is selective for DPP-IV over other DPP isozymes and proline specific serine proteases, and which has oral bioavailability in preclinical species and in vivo efficacy in animal models. The mode of binding of the cis-2,5-dicyanopyrrolidine moiety was determined by X-ray crystallography. The hydrochloride salt of 1c was further profiled for development as a potential new treatment for type 2 diabetes.
DICYANOPYRROLIDINES AS DIPEPTIDYL PEPTIDASE IV INHIBITORS
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Page/Page column 28, (2008/06/13)
The invention provides compounds of formula (I), the prodrugs and stereoisomers thereof, and the pharmaceutically acceptable salts of the compounds, prodrugs, and stereoisomers, wherein wherein R is as defined herein; pharmaceutical compositions thereof;
