A versatile new synthesis of 4-aryl- and heteroaryl-[3,4-c]pyrrolocarbazoles by [4+2] cycloaddition followed by palladium catalysed cross coupling

4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione Inhibitors of the Checkpoint Kinase Wee1. Structure−Activity Relationships for Chromophore Modification and Phenyl Ring Substitution

“…The best DNA-damaging agent(s) for use in conjunction with a Wee1 inhibitor may well turn out to be different from those for use with a Chk1 inhibitor, and the optimum relative timing of administration of the checkpoint abrogator and DNA-damaging agent may not be the same for Wee1 and Chk1 inhibitors. The synthesis of a series of related compounds lacking the 9-hydroxyl group as potential protein kinase C inhibitors has been reported, 16 but no biological data were provided.…”

Rapid analogue syntheses of heteroaromatic compounds

“…The initial 3-hydroxy-2-pyridones were readily transformed to the triflates, amongst the first examples of these compounds to be reported, which were used Analogues of the protein kinase C inhibitor staurosporin were made at Synthélabo starting with the Diels-Alder cycloaddition of N-methylmaleimide and 2-vinylindoles, leading to the triflate or bromide 45 after aromatisation. 153 Suzuki and Stille cross-couplings to the substrates 45 were successful (5 examples, 67-95%). Substituted 3-bromopyrazoles were assembled starting with the 1,3-dipolar cycloaddition of a bromonitrilimine with alkynes or alkenes.…”

Synthesis of pyrrolocarbazoles with N-substituted alkynyl-, alkylcyano- and alkylhydroxyl-groups

“…It should be noted that the pyrrolocarbazole core, apart from its ubiquitous role in natural products, 11 has seen frequent prior application in medicinal chemistry, 12 with particular emphasis as kinase inhibitors. Examples include earlier work focused on protein kinase C, [13][14] the checkpoint kinase Wee1 15 and Chk1 [16][17][18][19][20] , mixed lineage kinase (MLK) 21 inhibitors, as well as other series with more generic anti-cancer applications. [22][23] Similar scaffolds have also been identified as PARP-1 inhibitors.…”

“…Alternatively, approach B would generate the desired compounds with the desired N-functionalizations already in place on the 2-vinylindole precursor 9b. It should be noted that the Diels-Alder/aromatization strategy has been effectively utilized before to efficiently deliver substituted pyrrolocarbazoles (see the examples listed in the following references [13][14][15][17][18][21][22]24 and the following examples which include related modifications [29][30][31][32] with respect to the 2-vinylindole motif 33 ).…”