SYNTHESIS AND ANTITUMOR-ACTIVITY OF 1-[[(DIALKYLAMINO)ALKYL]AMINO]-4-METHYL-5H-PYRIDO[4,3-B]BENZO[E])INDOLE AND 1-[[DIALKYLAMINO)ALKYL]AMINO]-4-METHYL-5H-PYRIDO[4,3-B]-BENZO[G])INDOLE - A NEW CLASS OF ANTINEOPLASTIC AGENTS

The thermal Fischer indolization of hydrazones resulting from 4-hydrazino-5-methyl-1H-pyridin-2-one and various β- and α-tetralones led to 4-methyl-6,7-dihydro-2H,5H-pyrido[4,3-b]benzo[e]indol-l-ones and 4-methyl-10,11-dihydro- 2H,5H-pyrido[4,3-b]benzo[g]indol-l-ones, respectively. After aromatization, these compounds were transformed by phosphorus oxychloride, giving l-chloro-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g]indoles which were substituted by [(dialkylamino)alkyl]amines. The resulting l-[[(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. © 1990, American Chemical Society. All rights reserved.