Synthesis and in vitro antitumor evaluation of some indeno[1,2-c]-pyrazol(in)es substituted with sulfonamide, sulfonylurea(-thiourea) pharmacophores, and some derived thiazole ring systems

The synthesis of a series of 3-(4-chlorophenyl)-[1,2-c]pyrazol(in)es substituted with benzenesulfonamide, N-1,N-3-disubstituted sulfonylurea, sulfonylthiourea pharmacophores, and some derived thiazolidinone and thiazoline ring systems is described. All the newly synthesized target compounds were subjected to the NCI-in vitro disease-oriented antitumor screening to be evaluated for their antitumor activity. Eight compounds namely; 2-4, 7, 8, 10, 13, and 16; showed promising broad spectrum antitumor activity against most of the tested subpanel tumor cell lines (GI(50) < 100 mu M). Compound 3, 4-(3-(4-chlorophenyl)-4H-indeno[1,2-c]pyrazol2-yl)-benzenesulfonamide; although it did not show the highest growth inhibitory value (GI(50) (MG-MID) 13.2 mu M), it proved to be the most active analog in this study with the highest cytostatic and cytotoxic potentials (TGI and LC50 (MG-MTD) concentrations of 33.1 and 66.1 mu M, respectively). In general, the oxidized pyrazoles displayed better antitumor activity than their parent pyrazoline analogs, whereas the benzenesulfonamides and the N-1, N-3-disubstituted sulfonylureas showed significant better antitumor spectrum than the sulfonylthioureido and the derived thiazole analogs. (c) 2006 Elsevier Ltd. All rights reserved.