Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents
| Autor: | J.-M. Lhoste, François Lavelle, Emile Bisagni, Chi Hung Nguyen, Marie-Christine Bissery |
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| Rok vydání: | 1990 |
| Předmět: |
chemistry.chemical_classification
Leukemia Experimental Chemical Phenomena Pyridines Stereochemistry Aromatization Antineoplastic Agents Biological activity Chemical synthesis Mice Inbred C57BL Chemistry Mice Structure-Activity Relationship chemistry.chemical_compound Polycyclic compound chemistry Mice Inbred DBA Drug Discovery Tumor Cells Cultured Animals Molecular Medicine Structure–activity relationship Hydrobromic acid Alkyl Demethylation |
| Zdroj: | Journal of Medicinal Chemistry. 33:1519-1528 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00167a037 |
| Popis: | The thermal Fischer indolization of hydrazones resulting from 4-hydrazino-5-methyl-1H-pyridin-2-one and various beta- and alpha-tetralones led to 4-methyl-6,7-dihydro-2H,5H-pyrido[4,3- b]benzo[e]indol-1-ones and 4-methyl-11-dihydro-2H,5H-pyrido[4,3- b]benzo[g]indol-1-ones, respectively. After aromatization, these compounds were transformed by phosphorus oxychloride, giving 1-chloro-4-methyl-5H-pyrido[4,3- b]benzo[e]- and -benzo[g]indoles which were substituted by [(dialkylamino)alkyl]amines. The resulting 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido- [4,3-b]benzo[e]- and -benzo[g]indoles, as well as hydroxy derivatives obtained by demethylation of methoxylated compounds with hydrobromic acid, were tested for antitumor activity in vitro (leukemic and solid tumor cells) and in vivo on various experimental tumor models using the standard NCI protocols. 1-[[3-(Dialkylamino)propyl]-amino]-4-methyl-9-hydroxy-5H-pyrido[4,3- b]benzo[e]indoles appeared as a promising new class of antineoplastic agents. |
| Databáze: | OpenAIRE |
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