Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Starting from 2-(2-aminoethyl)-6-methoxy-1-methylcarbazole, ethyl 9-methoxy-5-methyl-6H-pyrido[4,3-b]carbazole-1-carboxylate was obtained through a three-step sequence. This compound and its 6-methyl derivative react with (dialkylamino)alkylamines to provide various 9-methoxy-5-methyl-6H-pyrido[4,3-b]carbazole-1-(N-substituted carboxamides) whose boron tribromide demethylation afforded corresponding 9-hydroxy-1-(N-substituted carbamoyl)-olivacines. The same pathway but starting from 2-(2-aminoethyl)-6-methoxy-1,4-dimethylcarbazole led to ethyl 9-methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole-1-carboxylate which did not normally react with amines. It provided either the recovered starting material at 120 degrees C or 9-methoxyellipticine resulting from an unexpected decarboethylation in a steel vessel at 180 degrees C. Biological testing of the newly obtained 1-carbamoylolivacine derivatives showed that 9-hydroxylated compounds displayed high cytotoxicity for cultured L1210 and colon 38 cells (IC50 range 5-10 nM) and good antitumor activity in vivo in the P388 leukemia and colon 38 models when administered by the iv route. The most active compound in these series is 9-hydroxy-5,6-dimethyl-1-[N-[2-(dimethylamino)ethyl]carbamoyl]-6H- pyrido[4,3-b]carbazole which was selected for further evaluation on murine solid tumors and for toxicological studies.
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PMID:Synthesis and evaluation of 9-hydroxy-5-methyl-(and 5,6-dimethyl)-6H-pyrido[4,3-b]carbazole-1-N- [(dialkylamino)alkyl]carboxamides, a new promising series of antitumor olivacine derivatives. 805 91

A keystone of this work was a modification of synthesis of the title compounds, which were used as substrates for the preparation of amides 5, 9-methoxyolivacine (4a) and ethyl 9-methoxy-5-methyl-6H-pyrido[4,3-b]carbazole-1-carboxylate (4b) were obtained in good overall yields (4a--72%, and 4b--31%) on alternative ways of the synthesis. The pilot results of the cytostatic activity of iminium salts 12a (IC50 = 8 microM) and 12b (IC50 = 2 microM) were determined on L1210 mouse leukaemia cells.
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PMID:An alternative way of the synthesis of 1-substituted 9-methoxy-5-methyl-6H-pyrido[4,3-b]carbazole derivatives. 1619 13