Synthesis and antitumor properties of new 4-methyl-substituted- pyrido[4,3-b]indoles (gamma-carbolines).
A new class of antineoplastic agents, 4-methyl-pyrido[4,3-b]indoles (5) and the related 4-hydroxymethyl derivatives (7), has been synthesized by a new pathway. Key transformations include regiospecific chlorination at the C(4)-position of 3-nitro-4-hydroxy-5-methyl-pyridin-2-(1H)-one (11) and photochemical cyclization of the intermediate triazolopyridones (15). This new synthesis was developed since an attempt to prepare 4-hydrazino-5-ethoxymethyl-pyridin-2-(1H)-one (10b) by the method previously used to obtain 4-hydrazino-5-methyl-pyridin-2-(1H)-one (10a) failed. The biological results obtained in different in vitro and in vivo models indicate that the substitution of the 4-CH3 by a 4-CH2OH group leads to a decrease of the antitumor properties.
Nguyen
C H
CH
URA 1387 CNRS, Synthèse Organique, Institut Curie, Orsay, France.
Bisagni
E
E
Lavelle
F
F
Bissery
M C
MC
Huel
C
C
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002243:Carbolines / Q000138:chemical synthesis* / Q000494:pharmacology; D007941:Leukemia P388 / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002243:Carbolines