Synthesis and antimycobacterial evaluation of new (2-oxo-2H-chromen-3-yl) substituted fluoroquinolones

• Published in: Journal of fluorine chemistry 2018-04, Vol.208, p.15-23
• Main Authors: Charushin, Valery N., Mochulskaya, Nataliya N., Antipin, Fedor V., Kotovskaya, Svetlana K., Nosova, Emiliya V., Ezhikova, Marina A., Kodess, Mikhail I., Kravchenko, Marionella A.
• Format: Article
• Language: English
• Subjects: (2-oxo-2H-chromen-3-yl)-substituted fluoroquinolones; 1,4-dihydro-benzoxepino[2,3-g]quinolones; Benzene; Bioactive compounds; Biological activity; Chemical synthesis; Condensates; Condensation products; Fluorides; Fluorine; Fluoroquinolones; Hydrocarbons; In vitro activity; Intermediates; Multidrug resistant organisms; Multidrug-resistant tuberculosis; Quinolones; Reaction intermediates; Substitution reactions; Temperature; Tuberculosis
• ISSN: 0022-1139; 1873-3328
• DOI: 10.1016/j.jfluchem.2018.01.007

[Display omitted] •The cyanomethyl fragment was incorporated into the benzene ring of fluoroquinolones.•Cyanomethyl fluoroquinolones was converted to (2-oxo-2H-chromen-3-yl) fluoroquinolones.•Substitution of another fluorine atom provides 1,4-dihydro[1]-benzoxepino[2,3-g]quinolones.•Some of new fluoroquinolones exhibit antimicobacterial activity. An efficient method for incorporation of the cyanomethyl fragment into the benzene ring of bi- and tricyclic fluoroquinolones through the nucleophilic substitution of a fluorine atom with carbanions derived from CH-active cyanoacetates, followed by an acidic hydrolysis of the reaction intermediates was developed. The reaction of cyanomethyl derivatives of bi- and tricyclic fluoroquinolones with ortho-hydroxy substituted benzaldehydes proved to give the corresponding condensation products, which can be regarded as the key intermediates in the synthesis of previously unknown (2-oxo-2H-chromen-3-yl) substituted bi- and tricyclic fluoroquinolones. It has been shown that an increase in the reaction temperature and exposition time promotes the competitive process, leading to substitution of one more fluorine atom to give 1,4-dihydro[1]-benzoxepino[2,3-g]quinolones. New fluoroquinolones proved to exhibit anti-mycobacterial activity, thus indicating that a search of biologically active compounds in this family of heterocycles appears to be a reasonable approach.