Synthesis, antimicrobial activity and acid dissociation constants of methyl 5, 5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylate derivatives. Issue 5 (1st March 2018)

• Record Type: Journal Article
• Authors: Nural, Yahya; Gemili, Muge; Ulger, Mahmut; Sari, Hayati; De Coen, Laurens M.; Sahin, Ertan
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 5(2018)
• Page Start: 942
• Page End: 946
• Publication Date: 2018-03-01
• Subjects: M. tuberculosis H37Rv -- Antimicrobial -- Acid dissociation constant -- Pyrrolidine -- Thiazole; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.01.045
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Novel methyl 5, 5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylates were reported. Novel antimycobacterial agents against M. tuberculosis H37Rv strains were reported. Antibacterial and antifungal activity was assessed. Acid dissociation constants of the compounds were determined. X-ray study was performed to confirm the stereochemistry. Abstract: In this study, a series of polysubstituted methyl 5, 5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylate derivatives were designed and synthesized by the cyclization reaction of methyl 1-(benzoylcarbamothioyl)-5, 5-diphenylpyrrolidine-2-carboxylates and 2-bromo-1-(4-substituted phenyl)ethanones in 70–96% yield. The starting pyrrolidine derivatives were synthesized via a 1, 3-dipolar cycloaddition reaction in 83–88% yield. The stereochemistry of one of these methyl 5, 5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylate derivatives was characterized by a single crystal X-ray diffraction study and the acid dissociation constants of these compounds were determined. An antimicrobial screening was performed against different bacterial and fungal strains and against the M. tuberculosis H37Rv strain. Interesting antibacterial activity was observed for two compounds against the A. baumannii strain with MIC values of 31.25 µg/mL (Ampicillin: 125 µg/mL) and against the M. tuberculosis H37Rv strain with MIC values of 0.98–1.96 µg/mL (Isoniazid: 0.98 µg/mL, Ethambutol: 1.96 µg/mL). Therefore, these structures can be considered as good starting points for the development of new powerful antimycobacterial agents.