Synthesis and evaluation of 2,4,5-trisubstitutedthiazoles as carbonic anhydrase-III inhibitors

• Main Authors: Bilal A. Al-Jaidi, Pran Kishore Deb, Soha Taher Telfah, Abdel Naser Dakkah, Yazan A. Bataineh, Qutaiba Ahmed Al Khames Aga, Mohammad A. Al-dhoun, Ala’ Ali Ahmad Al-Subeihi, Haifa’a Marouf Odetallah, Sanaa K. Bardaweel, Raghuprasad Mailavaram, Katharigatta N. Venugopala, Anroop B. Nair
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2020-01-01
• Series: Journal of Enzyme Inhibition and Medicinal Chemistry
• Subjects: carbonic anhydrase iii inhibitors; 2-amino-5-aryl-thiazole; hummel–dreyer method of chromatography
• Online Access: http://dx.doi.org/10.1080/14756366.2020.1786820

A series of 17 compounds (12–16 b) with 2,4,5-trisubstitutedthiazole scaffold having 5-aryl group, 4-carboxylic acid/ester moiety, and 2-amino/amido/ureido functional groups were synthesised, characterised, and evaluated for their carbonic anhydrase (CA)-III inhibitory activities using the size exclusion Hummel–Dreyer method (HDM) of chromatography. Compound 12a with a free amino group at the 2-position, carboxylic acid moiety at the 4-position, and a phenyl ring at the 5-position of the scaffold was found to be the most potent CA-III inhibitor (Ki = 0.5 μM). The presence of a carboxylic acid group at the 4-position of the scaffold was found to be crucial for the CA-III inhibitory activity. Furthermore, replacement of the free amino group with an amide and urea group resulted in a significant reduction of activity (compounds 13c and 14c, Ki = 174.1 and 186.2 μM, respectively). Thus, compound 12a (2-amino-5-phenylthiazole-4-carboxylic acid) can be considered as the lead molecule for further modification and development of more potent CA-III inhibitors.