An efficient synthesis of aryloxyphenyl cyclopropyl methanones: a new class of anti-mycobacterial agents

• Published in: Bioorganic & medicinal chemistry letters 2005-10, Vol.15 (20), p.4526-4530
• Main Authors: Dwivedi, Namrata, Tewari, Neetu, Tiwari, V.K., Chaturvedi, Vinita, Manju, Y.K., Srivastava, A., Giakwad, A., Sinha, S., Tripathi, R.P.
• Format: Article
• Language: English
• Subjects: Animals; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antitubercular Agents - chemical synthesis; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; Biological and medical sciences; Medical sciences; Methane - chemistry; Mice; Microbial Sensitivity Tests; Mycobacterium; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Pharmacology. Drug treatments; Phenyl cyclopropyl methanones; Tetrabutylammonium bromide; Tuberculosis; Wolf–Kishner reduction
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.07.007

Aryloxy phenyl cyclopropyl methanones were synthesized and evaluated as new potent anti-tubercular agents. An efficient, high yield and one-pot synthesis of phenyl cyclopropyl methanones by reaction of different aryl alcohols with 4′-fluoro-4-chloro-butyrophenone in THF/DMF in the presence of NaH/TBAB is reported. Most of the methanones were further reduced to respective alcohols or methylenes. All the compounds were evaluated for their anti-tubercular activities against M. tuberculosis H37Rv in vitro displaying MICs ranging from 25 to 3.125 μg/mL. The most active compounds showed activity against MDR strains and two of them ( 14 and 16) showed marginal enhancement of MST in mice.