179007-59-1Relevant articles and documents
Synthesis of 2-piperidinecarboxylic acid derivatives as potential anticonvulsants
Ho, Bin,Venkatarangan, Prabha M.,Cruse, Sharon F.,Hinko, Christine N.,Andersen, Peter H.,Crider, Albert M.,Adloo, Ahmad A.,Roane, David S.,Stables, James P.
, p. 23 - 31 (2007/10/03)
A variety of 2-piperidinecarboxamides were synthesized and evaluated for anticonvulsant activity using the MES and sc PTZ tests in mice and rats. Neurotoxicity was determined by the rotorod test. Several N-(benzyl)-2- piperidinecarboxamides exhibited potent MES activity in mice [2-CF3 14, ED50 = 29 mg/kg; 3-F 16, ED50 = 31 mg/kg; and 3-CF3 17, ED50 = 24 mg/kg]. The most active compounds in the MES test in mice were the 2,6- dimethylanilides [(R,S)-34, ED50 = 5.8 mg/kg; (R)-35, ED50 = 5.7 mg/kg; and (S)-36, ED50 = 14.8 mg/kg]. The enantiomer (S)-36 was about two-fold less potent in the MES test than (R)-35 and also was less neurotoxic. Acylation of the piperidine ring nitrogen of 12 anal 34 led to a decrease in the MES activity. In the N-(α-methylbenzyl)-2-piperidine-carboxamides, the stereochemistry at either the 2-position of the piperidine ring or at the α- position of the N-(α-methylbenzyl) group does not significantly affect MES activity.
Structure-based design and synthesis of substituted 2-butanols as nonpeptidic inhibitors of HIV protease: Secondary amide series
Reich, Siegfried H.,Melnick, Michael,Pino, Mark J.,Fuhry, Mary Ann M.,Trippe, Anthony J.,Appelt, Krzysztof,Davies II, Jay F.,Wu, Bor-Wen,Musick, Linda
, p. 2781 - 2794 (2007/10/03)
The design, synthesis, and crystallographic analysis of protein- inhibitor complexes is described for a novel series of nonpeptidic HIV protease (HIV Pr) inhibitors. Beginning with a cocrystal structure of a Phe- Pro peptidomimetic bound to the HIV Pr, design was initiated that resulted in the substituted 2-butanol compound 8 as the lead compound (K(i) = 24.5 μM, racemic mixture). Modifications on the initial compound were then made on the basis of its cocrystal structure with HIV Pr and inhibition data, resulting in compounds with enhanced potency against the enzyme (compound 18, K(i) = 0.48 μM). These inhibitors were found to bind to the enzyme essentially as predicted on the basis of the original design hypothesis. Stereospecific synthesis of individual enantiomers confirmed the prediction of a binding preference for the S alcohol stereochemistry. Modest antiviral activity was demonstrated for several of the more potent HIV Pr inhibitors in a HIV-1 infected CEM-SS cell line.
ENANTIOMERIC QUANTIFICATIONS OF AMINO ACIDS THROUGH THEIR Nα-ACYL AMIDES BY GAS CHROMATOGRAPHY.
Hosten, N.,Anteunis, M. J. O.
, p. 45 - 47 (2007/10/02)
Apparent separation of 1.1 or higher on Chiralsil Val III can be obtained for Nα-acyl N-alkyl aminoacid amides allowing the use of short capillary gas chromatographic columns.A clean derivatization protocol without racemization is described, proceding through the NCA derivatives that are prepared from "in situ" silylated amino acids with trimethylsilyl cyanide.
