A series of novel 3-(indol-1-yl)prop-1-yn-1-yl-substituted phthalazines and related azines was prepared via a concise pathway by palladium-catalyzed cross-coupling of appropriate halo-azines and N-propargylindoles. Some of the compounds exhibited significant antitumor activity in an in-vitro assay.

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Thermally induced [4+2] cycloaddition reactions of 5-ethanesulfonyl-2-methylpyridazin-3(2H)-one (2) with pyrano[3,4-b]indol-3(9H)-ones (1, 4) affords isomeric pyridazino[4,5-b]carbazolones (3a,b, 5a,b), the product ratio depending on the substitution pattern of the diene. Two carbazolocarbazoles (6, 7) were obtained as side products. The antineoplastic activity of ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole) has stimulated considerable interest in the field of b-fused carbazoles and has led to the synthesis of a large number of derivatives of the natural lead compound, some of them with superior antitumor properties. 1,2 Among those congeners, also some aza-analogous ellipticines like 6,11-dimethyl-5H-pyrido[3',4':4,5]pyrrolo-[2,3-g]isoquinoline 3 (9-azaellipticine), the drug candidate pazelliptine, 4 or a series of 1,4-dialkoxypyridazino[4,5-b]carbazoles 5 have been described. Whereas the latter 3-azaellipticines had been found to be almost inactive, 5 several new representatives of this ring system were prepared in our laboratory recently 6 and some of them turned out to be remarkably active in an in-vitro assay. In this context, the examination of alternative pathways to this tetracyclic ring system became an object of interest. In particular, a cycloaddition reaction between a synthon with a preformed pyridazine ring and another component representing the remaining part of the tetracyclic system was considered a promising strategy. As an indole-derived diene, an appropriately substituted pyrano[3,4-b]indol-3(9H)-one should be a useful building block, as such compounds had already been employed for the construction of condensed or substituted carbazoles previously, e.g. by Plieninger, 7 Moody, 8 and Pindur. 9 As the dienophile, we chose the electron-deficient 5-ethanesulfonyl-2-methylpyridazin-3(2H)-one, 10 which-as well as one example of a nitro-substituted pyridazinone 11-had been shown to react with simple butadiene derivatives in a Diels-Alder fashion to afford (tetrahydro-)phthalazinones, due to its low LUMO energy. 12,13

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A series of tetra-and pentacyclic imides with a carbazole skeleton and a basic side chain at the imide nitrogen was synthesized by cyclization of carbazole-2,3-dicarboxylic acid esters with an appropriate amine or via an N-aminoimide as a reactive intermediate. The target compounds 6 and 9 were tested in vitro for tumor cell-growth inhibition