97975-57-0Relevant academic research and scientific papers
Constrained peptidomimetics reveal detailed geometric requirements of covalent prolyl oligopeptidase inhibitors
Lawandi, Janice,Toumieux, Sylvestre,Seyer, Valentine,Campbell, Philip,Thielges, Sabine,Juillerat-Jeanneret, Lucienne,Moitessier, Nicolas
experimental part, p. 6672 - 6684 (2010/04/28)
Prolyl oligopeptidases cleave peptides on the carboxy side of internal proline residues and their inhibition has potential in the treatment of human brain disorders. Using our docking program FITTED, we have designed a series of constrained covalent inhibitors, built from a series of bicyclic scaffolds, to study the optimal shape required for these small molecules. These structures bear nitrile functional groups that we predicted to covalently bind to the catalytic serine of the enzyme. Synthesis and biological assays using human brain-derived astrocytic cells and endothelial cells and human fibroblasts revealed that these compounds act as selective inhibitors of prolyl oligopeptidase activity compared to prolyl-dipeptidyl-aminopeptidase activity, are able to penetrate the cells and inhibit intracellular activities in intact living cells. This integrated computational and experimental study shed light on the binding mode of inhibitors in the enzyme active site and will guide the design of future drug-like molecules.
(2S,5R/2R,5S)-Aminoethylpipecolyl aepip-aegPNA chimera: Synthesis and duplex/triplex stability
Shirude, Pravin S.,Kumar, Vaijayanti A.,Ganesh, Krishna N.
, p. 9485 - 9491 (2007/10/03)
This article reports the design and facile synthesis of novel chiral six-membered PNA analogues (2S,5R/2R,5S)-1-(N-Boc-aminoethyl)-5-(thymin-1-yl) pipecolic acid, aepipPNA IV that upon incorporation into standard aegPNA sequences effected stabilization of
Stereoselective synthesis of the cis-275B decahydroquinoline ring system
Banner, Edith J.,Stevens, Edwin D.,Trudell, Mark L.
, p. 4411 - 4414 (2007/10/03)
The Diels-Alder precursor was constructed from readily available D-glutamic acid utilizing a series of functional group transformations. The stereocenter of the amino acid provided the desired stereochemistry at C2 and diastereoselectively directed the in
THIAZOLIDINE DERIVATIVES
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, (2008/06/13)
An object of the present invention is to provide novel thiazolidine derivatives which are useful as drugs. The thiazolidine derivatives according to the present invention are compounds represented by the following general formula [I] and salts thereof, wherein R 1is alkyl, hydroxy, alkoxy, alkoxyalkyl, phenyl, phenylalkyl, phenylalkoxy, phenoxy, phenoxyalkyl, amino, alkylamino or a nonaromatic heterocycle; R 2is H or alkyl; R 3is H, alkyl or phenyl; R 4is H or alkyl; R 5is alkyl, halogenoalkyl, hydroxy, alkoxy, phenyl, phenylalkoxy, phenoxy, carboxyl, alkoxycarbonyl, phenylalkoxycarbonyl or an aromatic heterocycle; A 1is alkylene; and A 2is alkylene.
