N-substituted 2′-(aminoaryl)benzothiazoles as kinase inhibitors: Hit identification and scaffold hopping

Substituted 2-arylbenzothiazoles as kinase inhibitors: Hit-to-lead optimization

“…1 Serine/Threonine and tyrosine kinases of the Aurora and ErbB family, respectively, are described to be potential targets for treating different kind of cancer diseases like colorectal or non-small-cell lung cancer, glioblastoma, breast and colon cancer. [2][3][4][5][6] Aurora A and B expression is low or undetectable in resting cells, they play crucial roles in the G2 and mitotic phases of the cell cycle, and were found to be overexpressed in certain cancer types.…”

“…6 Based on our initial investigations into inhibition profiles for different adenine mimics being N-attached to 4-(benzothiazol-2 0 -yl)-and 3-(benzothiazol-2 0 -yl)-anilines, quinazoline scaffolds proved to be promising for further optimization attempts. 1 As an excellent starting point the 6 0 ,7 0 -dimethoxyquinazoline unit was identified (Table 1), giving rise to in vitro IC 50 values down to 135 nM on Aurora B (entry 1) and even 63 nM on EGFR (entry 4)-even though with virtually no inhibition of ErbB2. The 4 0 -(arylamino)-quinazoline structure is already known to possess a potential for good to excellent inhibitory activities on EGFR, 10,11 which was confirmed in our series as well.…”

Synthesis and antitumor activity evaluation of new 2-(4-aminophenyl)benzothiazole derivatives bearing different heterocyclic rings

“…2-(4-Aminophenyl)benzothiazole structure is known with high antitumor activity since 1996 [1][2][3][4][5] . Unexpectedly, it was found that, 2-(4-aminophenyl)benzothiazole derivatives inhibit cancer cell growth with nanomolar scale against a large panel of human cancer cell lines particularly against breast, colon and ovarian cell lines in in vitro anticancer screening program of the National Cancer Institute (NCI) with a characteristic biphasic doseresponse relationship 6,7 .…”

Synthesis and Antitumor Activity Evaluation of New 2-(4-aminophenyl) benzothiazole/oxazole/imidazole Derivatives

“…The structural simplicity and synthetic accessibility of benzothiazole (1)(2)(3)(4) ,benzoxazole and benzimidazole series show remarkable antitumor properties. A series of potent and selective agents derived from 2-(4-Aminophenyl)benzothiazole structure was extensively examined and developed during recent years to have antitumor activity since 1996 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) , Unexpectedly, it was found that , 2-(4-aminophenyl) benzothiazole and related structure derivatives inhibit cancer cell growth with nanomolar scale against a large panel of human cancer cell lines particularly against breast , colon and ovarian cell lines in in-vitro anticancer screening program of the National Cancer Institute (NCI) with a characteristic biphasic dose-response relationship. The original (unsubstituted) member of this series, 2-(4-aminophenyl) benzothiazole was considered to be ''Lead ''approach to drug discovery of new anticancer agents.…”