2-Aryl-N-(Phenylcarbamothioyl)quinoline carboxamides, N- (Thiazolyl IBenzothiazolyl carbamothioyl)cyclohexane carboxamides for Bio-appraisal: Design, Synthesis and Characterization

Abstract

Heterocycles bearing nitrogen and sulfur are the core structure of many biologically active compounds. The derivatives of quinoline, a well-known heterocycle, are recognized to have a wide range of uses in medicine, agriculture, and industries. The properties of these scaffolds piqued interest in using them to create possible bioactive chemicals. Quinoline scaffold was chosen to synthesize thiourea and amide derivatives due to its remarkable properties. Thiourea and amide derivatives are well known for their therapeutic and non-therapeutic potentials. Thioureas are also used as starting materials for synthesis of various heterocyclic compounds. Amides are mostly used as prodrugs for carboxylic acids or amines. 2-Phenylquinoline-4-carboxylic acid 132 was synthesized by a modification of Doebner method. Quinoline based thioureas 134a-i were synthesized by one pot reaction in which synthesized 2-phenylquinoline 4-carbonyl chloride 132a was reacted to KSCN and anilines. In same way quinoline based amides 136a-e were synthesized by reacting 2-phenylquinoline-4-carboxyl chloride 132a with anilines. Thiazoles scaffold is present in many natural compounds such as Y. ,amin B I and many FDA approved marketed drugs. The biological importance of thiazoles has ! attracted interest in selecting them to synthesize potential bio;:....,tive thiourea derivatives. In the-first series, 2-Aminobenzothiazoles 138a-b were synthesized by reacting ani line s 137a-h with KSCN and Bf2. Then in the second step cyclohexanecarboxylic acid 139 was converted to cyclohexyl isothiocyanate 139b in one pot reaction. Reaction with 2-aminobenzothiazoles generated corresponding thioureas 140a-h. In the second series, 4-aryl-2-aminothiazoles 142a-b were synthesized by reaction of thiourea with various phenacyl bromides 141a-b via Hantzsch thiazole reaction. Reaction of these thiazoles with cyclohexyl isothiocyanate in one-pot reaction generated series ofthiazole based thioureas 143a-b. The structures of synthesized compounds were characterized by physical parameters and spectroscopic techniques including FT-IR, IH-NMR and 13C-NMR. Biological activities of all synthesized thiourea and amide derivatives would be explored to establish structure activity relationship.