Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of indole-2-carboxylates were prepared and evaluated for their ability to inhibit the binding at the strychnine-insensitive glycine receptor that is associated with the NMDA-PCP-glycine receptor complex. All of the compounds were selective for the glycine site relative to other sites on the receptor macrocomplex and several of the compounds in this series were found to have submicromolar affinity for this receptor. The lead compound, 2-carboxy-6-chloro-3-indoleacetic acid (Ki = 1.6 microM vs [3H]glycine), was also found to noncompetitively inhibit the binding of MK-801, a ligand for the phencyclidine site on the receptor macrocomplex. These latter data suggest that the compound functions as an antagonist at the strychnine-insensitive glycine receptor. The structural activity relationships within this series of indole-2-carboxylates is discussed and several key pharmacophores are identified for this series of glycine ligands. In general, the most potent compounds were the C-3 acetamides, with N-propyl-2-carboxy-6-chloro-3-indoleacetamide having the highest receptor affinity.
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PMID:Novel indole-2-carboxylates as ligands for the strychnine-insensitive N-methyl-D-aspartate-linked glycine receptor. 184 94

1. Microsomal metabolism of 1-benzylpiperidine (1-BP), its cis-2,6-dimethyl (cis-2,6-DMBP), 4,4-dimethyl (4,4-DMBP), and alpha, alpha-dimethyl (alpha, alpha-DMBP) analogues, and phencyclidine (PCP) has been studied to assess the involvement of P450 oxidation of the enamine tautomers of the initial endocyclic iminium metabolites. 2. The selective prevention by cyanide of the metabolite production of 1-benzyl-3-piperidone but not 1-benzyl-3-piperidinol from 1-BP is consistent with the enamine as the source of the 3-one metabolite. 3. The parent amines and particularly the independently prepared iminium species induced a pattern of metabolism-dependent irreversible inactivation of P450 benz-phetamine demethylase activity, consistent with involvement of enamine C-3 oxidation in the inactivation process. 4. Substrate activity of the endocyclic enamines and alpha-aminoketones (presumably the enol-enamine tautomers) for horseradish peroxidase under conditions where simple aliphatic amines display no activity is consistent with metabolic one-electron oxidations of the enamines.
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PMID:Haemoprotein-mediated metabolism of enamines and the possible involvement of one-electron oxidations. 748 73

The asymmetric synthesis and biological activity of (2S,1'S,2'R,3'R)-2-(2'-carboxy-3'-hydroxymethylcyclopropyl) glycine ((+)-3) is described. This novel C-3' substituted carboxy cyclopropyl glycine is a highly potent group 2 and group 3 mGluR agonist that has proven to be orally active in both fear potentiated startle (animal model for anxiety) and PCP-induced motor activation (animal model for psychosis) assays in rats.
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PMID:(2S,1'S,2'R,3'R)-2-(2'-Carboxy-3'-hydroxymethylcyclopropyl) glycine is a highly potent group 2 and 3 metabotropic glutamate receptor agonist with oral activity. 1471 15