2-aminothiazoles in drug discovery: Privileged structures or toxicophores?. (1st October 2020)

• Record Type: Journal Article
• Authors: Jakopin, Žiga
• Is Part Of: Chemico-biological interactions. Volume 330(2020)
• Publication Date: 2020-10-01
• Subjects: ADR adverse drug reaction -- ANFT 2-amino-4-(5-nitro-2-furyl)thiazole -- COX cyclooxygenase -- GSH glutathione -- PD pharmacodynamic -- PK pharmacokinetic; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2020.109244
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: The 2-aminothiazole functionality has long been established as a privileged structural feature and therefore frequently exploited in the process of drug discovery and development. It has been introduced into numerous compounds due to its capacity for targeting a wide range of therapeutic target proteins. On the other hand, the aminothiazole group has also been classified as a toxicophore susceptible to metabolic activation and the ensuing reactive metabolite formation, hence caution is warranted when used in drug design. This review is divided into three parts entailing: ( i ) the general characteristics of the aminothiazole group, ( ii ) the advantages of the aminothiazole group in medicinal chemistry, and ( iii ) the impact of the integrated aminothiazole group on compound safety profile. Highlights: The advantages of the 2-aminothiazole group in medicinal chemistry were detailed. 2-aminothiazoles were studied as toxicophores that form reactive metabolites. Chemical strategies that reduce the intrinsic hepatotoxicity were highlighted.