Synthesis of thiophene-2-carboxamidines containing 2-amino-thiazoles and their biological evaluation as urokinase inhibitors

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Abstract

The serine protease urokinase (uPa) has been implicated in the progression of both breast and prostate cancer. Utilizing structure based design, the synthesis of a series of substituted 4-[2-amino-1,3-thiazolyl]-thiophene-2-carboxamidines is described. Further optimization of this series by substitution of the terminal amine yielded urokinase inhibitors with excellent activities.

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    Citation Excerpt :

    Some of the approved drugs having thiazole backbone are dasatinib (anticancer) [13], ritonavir (anti-HIV-1) [14] (1, Fig. 1), nizatidine (anti-ulcer) [15] and fentiazac (anti-inflammatory) [16]. In addition, numerous 1,3-thiazole analogues exhibit remarkable anti-HIV activity [17–19] (e.g: 2, IC50 HIV RT = 0.016 nM, Fig. 1) [20], besides many other pharmacological activities such as anti-cancer [21,22], urokinase inhibitors [23], anti-allergic [24], anti-oxidant [25], anti-inflammatory [26], analgesic [27], and anti-convulsant [28]. Thiazole-containing drug molecules are currently being used in the treatment of various central nervous system disorders [29].

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