824394-11-8Relevant articles and documents
Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular modeling investigation of novel dihydroisoxazole amino acids
Conti, Paola,De Amici, Marco,Grazioso, Giovanni,Roda, Gabriella,Pinto, Andrea,Hansen, Kasper B.?.,Nielsen, Birgitte,Madsen, Ulf,Br?uner-Osborne, Hans,Egebjerg, Jan,Vestri, Valentina,Pellegrini-Giampietro, Domenico E.,Sibille, Pauline,Acher, Francine C.,De Micheli, Carlo
, p. 6315 - 6325 (2005)
The four stereoisomers of 5-(2-amino-2-carboxyethyl)-4,5-dihydroisoxazole- 3-carboxylic acid-(+)-4, (-)-4, (+)-5, and (-)-5 were prepared by stereoselective synthesis of two pairs of enantiomers, which were subsequently resolved by enzymatic procedures. These four stereoisomers and the four stereoisomers of the bicyclic analogue 5-amino-4,5,6,6a-tetrahydro-3aH- cyclopenta[d]isoxazole-3,5-dicarboxylic acid (+)-2, (-)-2, (+)-3, and (-)-3 were tested at ionotropic and metabotropic glutamate receptor subtypes. The most potent NMDA receptor antagonists [(+)-2, (-)-4, and (+)-5] showed a significant neuroprotective effect when tested in an oxygen glucose deprivation (OGD) cell culture test. The same compounds were preliminarily assayed using Xenopus oocytes expressing cloned rat NMDA receptors containing the NR1 subunit in combination with either NR2A, NR2B, NR2C, or NR2D subunit. In this assay, all three derivatives showed high antagonist potency with preference for the NR2A and NR2B subtypes, with derivative (-)-4 behaving as the most potent antagonist. The biological data are discussed on the basis of homology models reported in the literature for NMDA receptors and mGluRs.
Diaminopimelic acid (DAP) analogs bearing isoxazoline moiety as selective inhibitors against meso-diaminopimelate dehydrogenase (m-Ddh) from Porphyromonas gingivalis
Ma, Hongguang,Stone, Victoria N.,Wang, Huiqun,Kellogg, Glen E.,Xu, Ping,Zhang, Yan
, p. 3840 - 3844 (2017/07/27)
Two diastereomeric analogs (1 and 2) of diaminopimelic acid (DAP) bearing an isoxazoline moiety were synthesized and evaluated for their inhibitory activities against meso-diaminopimelate dehydrogenase (m-Ddh) from the periodontal pathogen, Porphyromonas
Design, synthesis, and pharmacological characterization of novel, potent NMDA receptor antagonists
Conti, Paola,De Amici, Marco,Grazioso, Giovanni,Roda, Gabriella,Negra, Federico F. Barberis,Nielsen, Birgitte,Stensb?l, Tine B.,Madsen, Ulf,Br?uner-Osborne, Hans,Frydenvang, Karla,De Sarro, Giovambattista,Toma, Lucio,De Micheli, Carlo
, p. 6740 - 6748 (2007/10/03)
The two diastereomeric pairs of acidic amino acids 5-(2-amino-2- carboxyethyl)-4,5-dihydroisoxazole-3-carboxylic acid (8A/8B) and 4-(2-amino-2-carboxyethyl)-5,5-dimethyl-4,5-dihydroisoxazole-3-carboxylic acid (10A/10B) were prepared via a strategy based on a 1,3-dipolar cycloaddition. The four amino acids were tested at ionotropic and metabotropic glutamate receptors. None of the compounds was active, neither as agonists nor as antagonists, at 1 mM on metabotropic receptors (mGluR1, -2, -4, and -5 expressed in CHO cell lines). Conversely, the pair of stereoisomers 8A/SB showed a remarkable affinity, antagonist potency, and selectivity for NMDA receptors, when tested on ionotropic glutamate receptors. The affinity of 8A proved to be 5 times higher than that of diastereomer 8B (Ki values 0.21 and 0.96 ìè, respectively). Furthermore, compounds 8A and 8B exhibited a noteworthy anticonvulsant activity in in vivo tests on DBA/2 mice. Derivative 10A was inactive at all ionotropic glutamate receptors, whereas its stereoisomer 10B displayed a seizable binding to both NMDA and AMPA receptors.
Synthesis and testing of heterocyclic analogues of diaminopimelic acid (DAP) as inhibitors of DAP dehydrogenase and DAP epimerase
Abbott, Shaun D.,Lane-Bell, Patricia,Sidhu, Kanwar P. S.,Vederas, John C.
, p. 6513 - 6520 (2007/10/02)
Substrate analogues were synthesized and examined as inhibitors of diaminopimelic acid (DAP) dehydrogenase from Bacillus sphaericus and of DAP epimerase from Escherichia coli. These enzymes produce meso-DAP (3) (a precursor for L-lysine and for peptidogly
