Rostom Sherif A F
Department of Medicinal Chemistry, Faculty of Medicine, King Abdulaziz University, PO Box 80205, Jeddah 21589, Saudi Arabia.
Bioorg Med Chem. 2006 Oct 1;14(19):6475-85. doi: 10.1016/j.bmc.2006.06.020. Epub 2006 Jun 27.
The synthesis of a series of 3-(4-chlorophenyl)-[1,2-c]pyrazol(in)es substituted with benzenesulfonamide, N1,N3-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 (GI50 < 100 microM). Compound 3, 4-(3-(4-chlorophenyl)-4H-indeno[1,2-c]pyrazol- 2-yl)-benzenesulfonamide; although it did not show the highest growth inhibitory value (GI50 (MG-MID) 13.2 microM), it proved to be the most active analog in this study with the highest cytostatic and cytotoxic potentials (TGI and LC50 (MG-MID) concentrations of 33.1 and 66.1 microM, respectively). In general, the oxidized pyrazoles displayed better antitumor activity than their parent pyrazoline analogs, whereas the benzenesulfonamides and the N1, N3-disubstituted sulfonylureas showed significant better antitumor spectrum than the sulfonylthioureido and the derived thiazole analogs.
本文描述了一系列3-(4-氯苯基)-[1,2-c]吡唑(啉)类化合物的合成，这些化合物被苯磺酰胺、N1,N3-二取代磺酰脲、磺酰硫脲药效基团以及一些衍生的噻唑烷酮和噻唑啉环系统所取代。所有新合成的目标化合物都接受了美国国立癌症研究所（NCI）面向疾病的体外抗肿瘤筛选，以评估它们的抗肿瘤活性。有8种化合物，即2-4、7、8、10、13和16，对大多数测试的亚组肿瘤细胞系显示出有前景的广谱抗肿瘤活性（GI50 < 100 microM）。化合物3，4-(3-(4-氯苯基)-4H-茚并[1,2-c]吡唑-2-基)-苯磺酰胺；虽然它没有显示出最高的生长抑制值（GI50（MG-MID）为13.2 microM），但在本研究中它被证明是活性最高的类似物，具有最高的细胞生长抑制和细胞毒性潜力（TGI和LC50（MG-MID）浓度分别为33.1和66.1 microM）。一般来说，氧化的吡唑比其母体吡唑啉类似物显示出更好的抗肿瘤活性，而苯磺酰胺和N1,N3-二取代磺酰脲显示出比磺酰硫脲和衍生的噻唑类似物明显更好的抗肿瘤谱。
