Synthesis and Biological Importance of 2-(thio)ureabenzothiazoles

Abstract

The (thio)urea and benzothiazole (BT) derivatives have been shown to have a broad spectrum of biological activities. These groups, when bonded, result in the 2-(thio)ureabenzothizoles (TBT and UBT), which could favor the physicochemical and biological properties. UBTs and TBTs are compounds of great importance in medicinal chemistry. For instance, Frentizole is a UBT derivative used for the treatment of rheumatoid arthritis and systemic lupus erythematosus. The UBTs Bentaluron and Bethabenthiazuron are commercial fungicides used as wood preservatives and herbicides in winter corn crops. On these bases, we prepared this bibliography review, which covers chemical aspects of UBTs and TBTs as potential therapeutic agents as well as their studies on the mechanisms of a variety of pharmacological activities. This work covers synthetic methodologies from 1935 to nowadays, highlighting the most recent approaches to afford UBTs and TBTs with a variety of substituents as illustrated in 42 schemes and 13 figures and concluded with 187 references. In addition, this interesting review is designed on chemical reactions of 2-aminobenzothiazoles (2ABTs) with (thio)phosgenes, iso(thio)cyanates, 1,1′-(thio)carbonyldiimidazoles [(T)CDI]s, (thio)carbamoyl chlorides, and carbon disulfide. This topic will provide information of utility for medicinal chemists dedicated to the design and synthesis of this class of compounds to be tested with respect to their biological activities and be proposed as new pharmacophores.

Keywords

• 2-aminobenzothiazoles
• (thio)ureabenzothiazoles
• (thio)phosgene
• iso(thio)cyanates
• (thio)carbonyldiimidazoles
• carbamoyl chlorides