Synthesis, and structure-activity relationship for C(4) and/or C(5) thienyl substituted pyrimidines, as a new family of antimycobacterial compounds

Egor V Verbitskiy; Ekaterina M Cheprakova; Pavel A Slepukhin; Marionella A Kravchenko; Sergey N Skornyakov; Gennady L Rusinov; Oleg N Chupakhin; Valery N Charushin

doi:10.1016/j.ejmech.2015.05.007

Synthesis, and structure-activity relationship for C(4) and/or C(5) thienyl substituted pyrimidines, as a new family of antimycobacterial compounds

Eur J Med Chem. 2015 Jun 5:97:225-34. doi: 10.1016/j.ejmech.2015.05.007. Epub 2015 May 7.

Authors

Egor V Verbitskiy¹, Ekaterina M Cheprakova², Pavel A Slepukhin², Marionella A Kravchenko³, Sergey N Skornyakov³, Gennady L Rusinov², Oleg N Chupakhin², Valery N Charushin²

Affiliations

¹ I. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, S. Kovalevskoy Str., 22, Ekaterinburg, 620137, Russia; Ural Federal University, Mira St. 19, Ekaterinburg, 620002, Russia. Electronic address: Verbitsky@ios.uran.ru.
² I. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, S. Kovalevskoy Str., 22, Ekaterinburg, 620137, Russia; Ural Federal University, Mira St. 19, Ekaterinburg, 620002, Russia.
³ Ural Research Institute for Phthisiopulmonology, 22 Parts'ezda St., 50, Ekaterinburg, 620039, Russia.

PMID: 25982331
DOI: 10.1016/j.ejmech.2015.05.007

Abstract

Combination of the Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (SN(H)) reactions proved to be a convenient method for the synthesis of C(4) and/or C(5) mono(thienyl) and di(thienyl) substituted pyrimidines from commercially available 5-bromopyrimidine. All new pyrimidines were found to be active in micromolar concentrations in vitro against H37Rv, avium, terrae, rifampicin and isoniazid-resistance strains of Mycobacterium tuberculosis. The data for acute in vivo toxicity in mice have been obtained for these compounds which appear to be promising antitubercular agents.

Keywords: Antimicobacterial; Cross-coupling; Nucleophilic aromatic substitution of hydrogen; Pyrimidine; Tuberculosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antitubercular Agents / chemical synthesis*
Antitubercular Agents / chemistry
Antitubercular Agents / pharmacology
Drug Resistance / drug effects
Inhibitory Concentration 50
Mice
Molecular Structure
Mycobacterium tuberculosis / drug effects
Pyrimidines / chemical synthesis*
Pyrimidines / chemistry
Pyrimidines / pharmacology
Structure-Activity Relationship
Ticrynafen / chemistry*

Substances

Antitubercular Agents
Pyrimidines
Ticrynafen