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The Gramine Route to Pyrido[4,3-b]indol-3-ones – Identification of a New Cytotoxic Lead

By Uwe Wollein and Franz Bracher


A novel approach to 3-oxo-γ-carbolines was worked out starting from methyl indol-2-ylacetate via a gramine derivative. After quaternization, ammonia and 4-methoxybenzylamine could be inserted giving appropriate 3-oxo-γ-carbolines. Condensation with 2-chlorobenzaldehyde under microwave irradiation gave a 4-(2-chlorobenzyl)-3-oxo-γ-carboline. N-methylation lead to a product with very promising antifungal and cytotoxic activities

Topics: Research Article
Publisher: Österreichische Apotheker-Verlagsgesellschaft
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Provided by: PubMed Central

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  2. (2010). A versatile synthesis of 3-substituted 4-cyano-1,2,3,4-tetrahydro-1-oxo-β-carbolines. Synthesis.
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  4. (2010). Feigin A; Huntington Disease Study Group DIMOND Investigators. A randomized, placebo-controlled trial of latrepirdine in Huntington disease. Arch Neurol.
  5. (1992). Homolytic substitution reactions of electron-rich pentatomic heteroaromatics by electrophilic carboncentered radicals. Synthesis of alpha-heteroarylacetic acids.
  6. (1992). I: Synthese von 1-Aryl- und 1-Alkenyl-ß-carbolinen durch Palladium-katalysierte Kupplungsreaktionen. Liebigs Ann Chem.
  7. (1981). Metabolic activation of 1-methyl-3-amino-5H-pyrido[4,3-b]indole and several structurally related mutagens.
  8. (2007). Natural products as sources of new drugs over the last 25 years.
  9. (2008). New synthesis of pyrido[4,3-b]indoles (γ-carbolines) on the basis of indolin-2-one lactim ether. Russ Chem Bull.
  10. Novel 3-arylidene-indolin-2-ones as inhibitors of NAD +-dependent histone deacetylases (sirtuins).
  11. (1998). Novel and simple syntheses of 5H-pyrido[4,3-b]indole (γ-carboline) derivatives having a methoxycarbonyl group at the 4-position based on 1-hydroxyindole chemistry. Chem Pharm Bull.
  12. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods.
  13. (2007). ß-Carboline alkaloids: Biochemical and pharmacological functions. Curr Med Chem.
  14. (2005). Sunitinib malate. Drugs Fut.
  15. (2009). Synthesis and biological evaluation of novel γ-carboline analogues of Dimebon as potent 5-HT6 receptor antagonists. Bioorg Med Chem Lett.
  16. (1998). Synthesis and biological evaluations of 3-substituted indolin-2-ones: A novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases. J Med Chem.
  17. (1988). Synthesis of esters of 3-(2-aminoethyl)-1H-indole-2-acetic acid and 3-(2-aminoethyl)-1H-indole-2-malonic acid (= 2-[3-(2-aminoethyl)-1H-indol-2-yl]propanedioic acid). Helv Chim Acta.
  18. (2005). Synthesis of spirooxindoles via asymmetric 1,3-dipolar cycloaddition. Tetrahedron Lett.
  19. (2008). Synthesis, modeling, and RET protein kinase inhibitory activity of 3- and 4-substituted β-carbolin-1-ones. J Med Chem.
  20. (2007). The discovery of carboline analogs as potent MAPKAP-K2 inhibitors. Bioorg Med Chem Lett.
  21. (1995). Three explorative studies on the efficacy of the antihistaminic mebhydroline (Omeril). Int J Clin Pharmacol Ther.
  22. (2007). Total syntheses of the chlorinated β-carboline alkaloids bauerine
  23. (1980). Use of N,N-dimethyl(methylene)ammonium chloride in the functionalization of indoles. Heterocycles.
  24. (1994). β-Carbolines from the blue-green alga Dichothrix baueriana. J Nat Prod.