Synthesis of aza and carbocyclic β-carbolines for the treatment of alcohol abuse. Regiospecific solution to the problem of 3,6-disubstituted β- and aza-β-carboline specificity

Organic & Biomolecular Chemistry
V V N Phani Babu TiruveedhulaJames M Cook

Abstract

A novel two step protocol was developed to gain regiospecific access to 3-substituted β- and aza-β-carbolines, 3-PBC (1), 3-ISOPBC (2), βCCt (3), 6-aza-3-PBC (4) and 6-aza-3-ISOPBC (5). These β-carbolines (1-3) are potential clinical agents to reduce alcohol self-administration, especially 3-ISOPBC·HCl (2·HCl) which appears to be a potent anti-alcohol agent active against binge drinking in a rat model of maternally deprived (MD) rats. The method consists of two consecutive palladium-catalyzed reactions: a Buchwald-Hartwig amination followed by an intramolecular Heck-type cyclization in high yield.

References

Mar 26, 1998·Alcoholism, Clinical and Experimental Research·G F KoobF Weiss
May 29, 1999·Critical Reviews in Neurobiology·W J McBride, T K Li
Jun 27, 2000·Psychopharmacology·B A Johnson, N Ait-Daoud
Nov 30, 2000·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·H R Kranzler
Sep 12, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Harry L JunePhil Skolnick
Sep 18, 2004·The Journal of Organic Chemistry·Caroline MeyersRoger A Dommisse
Sep 29, 2004·Biochemical Pharmacology·George F Koob
Nov 24, 2004·Angewandte Chemie·C Oliver Kappe
Oct 28, 2005·Nature Neuroscience·George F Koob, Michel Le Moal
Sep 12, 2006·Biochemical Pharmacology·M C MoffettM J Kuhar
Feb 20, 2007·Current Medicinal Chemistry·Rihui CaoAnlong Xu
Mar 6, 2007·TheScientificWorldJournal·Patrice Venault, Georges Chapouthier
Nov 18, 2008·Trends in Genetics : TIG·Gursharan KalsiBrien P Riley
Apr 8, 2009·Journal of the American Chemical Society·Brett P ForsStephen L Buchwald
May 8, 2009·Chemical Society Reviews·Mandy-Nicole BirkholzPiet W N M van Leeuwen
Mar 4, 2011·Proceedings of the National Academy of Sciences of the United States of America·Juan LiuLaure Aurelian
Oct 25, 2011·Frontiers in Neuroscience·Andrew R S T YangHarry L June
Nov 15, 2012·Brain Research Bulletin·Jovana DivljakovićMiroslav M Savić
Dec 18, 2013·Alcoholism, Clinical and Experimental Research·Eileen K SawyerDonna M Platt
Oct 24, 2014·The Journal of Organic Chemistry·Ylva SunessonPer-Ola Norrby

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