Literature DB >> 26349488

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.

V V N Phani Babu Tiruveedhula1, Kashi Reddy Methuku1, Jeffrey R Deschamps2, James M Cook1.   

Abstract

A novel two step protocol was developed to gain regiospecific access to 3-substituted β- and aza-β-n class="Chemical">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.

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Year:  2015        PMID: 26349488      PMCID: PMC4704088          DOI: 10.1039/c5ob01572c

Source DB:  PubMed          Journal:  Org Biomol Chem        ISSN: 1477-0520            Impact factor:   3.876


  40 in total

Review 1.  Pharmacotherapy of alcoholism: gaps in knowledge and opportunities for research.

Authors:  H R Kranzler
Journal:  Alcohol Alcohol       Date:  2000 Nov-Dec       Impact factor: 2.826

2.  Little evidence of a role for the α1GABAA subunit-containing receptor in a rhesus monkey model of alcohol drinking.

Authors:  Eileen K Sawyer; Casey Moran; Madelynn H Sirbu; Melissa Szafir; Michael Van Linn; Ojas Namjoshi; V V N Phani Babu Tiruveedhula; James M Cook; Donna M Platt
Journal:  Alcohol Clin Exp Res       Date:  2013-12-13       Impact factor: 3.455

3.  Discriminative stimulus effects of zolpidem in squirrel monkeys: role of GABA(A)/alpha1 receptors.

Authors:  James K Rowlett; Roger D Spealman; Snjezana Lelas; James M Cook; Wenyuan Yin
Journal:  Psychopharmacology (Berl)       Date:  2002-11-06       Impact factor: 4.530

Review 4.  Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents.

Authors:  W J McBride; T K Li
Journal:  Crit Rev Neurobiol       Date:  1998

5.  Synthesis of novel 3-substituted beta-carbolines as benzodiazepine receptor ligands: probing the benzodiazepine receptor pharmacophore.

Authors:  M S Allen; T J Hagen; M L Trudell; P W Codding; P Skolnick; J M Cook
Journal:  J Med Chem       Date:  1988-09       Impact factor: 7.446

6.  Bite angle effects of diphosphines in C-C and C-X bond forming cross coupling reactions.

Authors:  Mandy-Nicole Birkholz; Zoraida Freixa; Piet W N M van Leeuwen
Journal:  Chem Soc Rev       Date:  2009-02-10       Impact factor: 54.564

7.  An efficient process for pd-catalyzed C-N cross-coupling reactions of aryl iodides: insight into controlling factors.

Authors:  Brett P Fors; Nicole R Davis; Stephen L Buchwald
Journal:  J Am Chem Soc       Date:  2009-04-29       Impact factor: 15.419

Review 8.  The role of GABAA receptors in mediating the effects of alcohol in the central nervous system.

Authors:  Martin Davies
Journal:  J Psychiatry Neurosci       Date:  2003-07       Impact factor: 6.186

Review 9.  Unraveling the molecular mechanisms of alcohol dependence.

Authors:  Gursharan Kalsi; Carol A Prescott; Kenneth S Kendler; Brien P Riley
Journal:  Trends Genet       Date:  2008-11-17       Impact factor: 11.639

Review 10.  From the behavioral pharmacology of beta-carbolines to seizures, anxiety, and memory.

Authors:  Patrice Venault; Georges Chapouthier
Journal:  ScientificWorldJournal       Date:  2007-02-19
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  1 in total

1.  Effects of the benzodiazepine GABAA α1-preferring antagonist 3-isopropoxy-β-carboline hydrochloride (3-ISOPBC) on alcohol seeking and self-administration in baboons.

Authors:  August F Holtyn; V V N Phani Babu Tiruveedhula; Michael Rajesh Stephen; James M Cook; Elise M Weerts
Journal:  Drug Alcohol Depend       Date:  2016-11-04       Impact factor: 4.492

  1 in total

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