title: Synthesis and antituberculosis activity of novel 5-styryl-4-(hetero)aryl-pyrimidines via combination of the Pd-catalyzed Suzuki cross-coupling and S(N)(H) reactions.
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 5-styryl-4-(hetero)aryl substituted pyrimidines from commercially available 5-bromopyrimidine. All intermediate 5-bromo-4-(hetero)aryl substituted pyrimidines and also the targeted 5-styryl-4-(hetero)arylpyrimidines were found to be active in micromolar concentrations in vitro against Mycobacterium tuberculosis H37Rv, avium, terrae, and multi-drug-resistant strain isolated from tuberculosis patients in Ural region (Russia). It has been found that some of these compounds possess a low toxicity and have a bacteriostatic effect, comparable and even higher with that of first-line antituberculosis drugs.
authors.affiliation: Ural Research Institute for Phthisiopulmonology, 22 Parts'ezda, 50, Ekaterinburg 620039, Russia.
authors.forename: Marionella A
authors.initials: MA
authors.lastname: Kravchenko
authors.affiliation: I. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, S. Kovalevskoy Str., 22, Ekaterinburg 620990, Russia; Ural Federal University, Mira St. 19, Ekaterinburg 620002, Russia. Electronic address: Verbitsky@ios.uran.ru.
authors.forename: Egor V
authors.initials: EV
authors.lastname: Verbitskiy
authors.affiliation: Ural Research Institute for Phthisiopulmonology, 22 Parts'ezda, 50, Ekaterinburg 620039, Russia.
authors.forename: Igor D
authors.initials: ID
authors.lastname: Medvinskiy
authors.affiliation: I. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, S. Kovalevskoy Str., 22, Ekaterinburg 620990, Russia; Ural Federal University, Mira St. 19, Ekaterinburg 620002, Russia.
authors.forename: Gennady L
authors.initials: GL
authors.lastname: Rusinov
authors.affiliation: I. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, S. Kovalevskoy Str., 22, Ekaterinburg 620990, Russia; Ural Federal University, Mira St. 19, Ekaterinburg 620002, Russia.
authors.forename: Valery N
authors.initials: VN
authors.lastname: Charushin
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002384:Catalysis; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D010165:Palladium / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D011743:Pyrimidines; D010165:Palladium
keywords: Antimicobacterial; Cross-coupling; Nucleophilic aromatic substitution of hydrogen; Pyrimidine; Tuberculosis