الفهرس 
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Abstract
In parts I–III of this investigation, 5 different series of 2,5-disubstituted quinoline derivatives (I-10a–g, I-11a–k, II-3a–o, III-4a–g, and III-5a–g) have been rationally designed, synthesized and evaluated for their antiproliferative activity over a panel of 60 cancer cell lines at NCI. Furthermore, the most potent compound in each series was profiled for its kinase inhibitory activity against a panel of oncogenic protein kinases. Compounds I-11b and I-11d, II-3j and III-5a, III-5d, and III-5g were found to be the most potent derivatives with superior potencies and efficacies than sorafenib and/or gefitinib. Kinase screening of compounds I-11d and III-5d disclosed its highly selective inhibitory effects against BRAFV600E /C-RAF and TrKA kinases, respectively. On the other hand, in the next sections (parts IV–VI of this study, diverse series of pyridylamide based benzothiazoles (IV-4a,b, IV-5, IV-6a–n, V-3a–i, V-4a–m, VI-4 and VI-5) have been rationally designed and synthesized as potent kinase inhibitors. The first series (IV-4a,b, IV-5 and IV-6a–n) was tailored to target both the wild ABL kinase and its gatekeeper mutant ABLT315I. The second series (V-3a–i and V-4a–m) has been designed and synthesized as dual B-RafV600E and C-Raf kinase inhibitors, where the aliphatic ureido motif of the previous series was replaced with aromatic amides V-3a–i and ureas V-3a–i. Finally, marginal change in the hydrophobic tail of V-4a led to discovery of a new nanomolar multikinase inhibitor VI-5 (KST016366).