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Biotech / Medical : Gliatech (GLIA) -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (720)	4/20/1999 12:39:00 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 2001

just parking this in hopes that it may be of interest or meaning, some day, to some of our pharmachemists or neurologists. Please don't surmise that it has meaning to me, as it's Greek. BTW.... JC Schwartz seems to be an author to follow re. Morriset et al.... J Med Chem 1999 Feb 25;42(4):593-600 Development of chiral N-alkylcarbamates as new leads for potent and selective H3-receptor antagonists: synthesis, capillary electrophoresis, and in vitro and oral in vivo activity. Sasse A, Kiec-Kononowicz K, Stark H, Motyl M, Reidemeister S, Ganellin CR, Ligneau X, Schwartz JC, Schunack W Institut fur Pharmazie I, Freie Universitat Berlin, Konigin-Luise-Strasse 2+4, D-14195 Berlin, Germany. Novel carbamates as derivatives of 3-(1H-imidazol-4-yl)propanol with an N-alkyl chain were prepared as histamine H3-receptor antagonists. Branching of the N-alkyl side chain with methyl groups led to chiral compounds which were synthesized stereospecifically by a Mitsunobu protocol adapted Gabriel synthesis. The optical purity of some of the chiral compounds was determined (ee > 95%) by capillary electrophoresis (CE). The investigated compounds showed pronounced to high antagonist activity (Ki values of 4.1-316 nM) in a functional test for histamine H3 receptors on rat cerebral cortex synaptosomes. Similar H3-receptor antagonist activities were observed in a peripheral model on guinea pig ileum. No stereoselective discrimination for the H3 receptor for the chiral antagonists was found with the in vitro assays. All compounds were also screened for central H3-receptor antagonist activity in vivo in mice after po administration. Most compounds were potent agents of the H3-receptor-mediated enhancement of brain Ntau-methylhistamine levels. The enantiomers of the N-2-heptylcarbamate showed a stereoselective differentiation in their pharmacological effect in vivo (ED50 of 0.39 mg/kg for the (S)-derivative vs 1.5 mg/kg for the (R)-derivative) most probably caused by differences in pharmacokinetic parameters. H1- and H2-receptor activities were determined for some of the novel carbamates, demonstrating that they have a highly selective action at the histamine H3 receptor.