100063-22-7Relevant articles and documents
2-Bromo-2-chloro-3-arylpropanenitriles as C-3 Synthons for the Synthesis of Functionalized 3-Aminothiophenes
Batsyts, Sviatoslav,Shehedyn, Maksym,Goreshnik, Evgeny A.,Obushak, Mykola D.,Schmidt, Andreas,Ostapiuk, Yurii V.
, p. 7842 - 7856 (2019/12/24)
2-Bromo-2-chloro-3-arylpropanenitriles can be prepared by Meerwein reaction from 2-chloroacrylonitrile and various aryldiazonium salts under copper(II) bromide catalysis. They proved to be stable compounds which form 2-chlorocinnnamonitriles upon treatment with bases. Reaction of the title compounds with substituted thioglycolates gave substituted 3-aminothiophenes which have not yet been accessible by other routes. Three-component reactions with the title compound, sodium sulfide and bromonitromethane, chloroacetonitrile, or ethyl 4-chloroacetoacetate gave 2-nitro- and 2-cyano-substituted 3-aminothiophenes, and thienopyridinediones in high yields and in one single step, respectively.
Design, Synthesis, and Biological Evaluation of 6-Substituted Thieno[3,2- d]pyrimidine Analogues as Dual Epidermal Growth Factor Receptor Kinase and Microtubule Inhibitors
Romagnoli, Romeo,Prencipe, Filippo,Oliva, Paola,Baraldi, Stefania,Baraldi, Pier Giovanni,Schiaffino Ortega, Santiago,Chayah, Mariem,Kimatrai Salvador, Maria,Lopez-Cara, Luisa Carlota,Brancale, Andrea,Ferla, Salvatore,Hamel, Ernest,Ronca, Roberto,Bortolozzi, Roberta,Mariotto, Elena,Mattiuzzo, Elena,Viola, Giampietro
supporting information, p. 1274 - 1290 (2019/01/30)
The clinical evidence for the success of tyrosine kinase inhibitors in combination with microtubule-targeting agents prompted us to design and develop single agents that possess both epidermal growth factor receptor (EGFR) kinase and tubulin polymerization inhibitory properties. A series of 6-aryl/heteroaryl-4-(3′,4′,5′-trimethoxyanilino)thieno[3,2-d]pyrimidine derivatives were discovered as novel dual tubulin polymerization and EGFR kinase inhibitors. The 4-(3′,4′,5′-trimethoxyanilino)-6-(p-tolyl)thieno[3,2-d]pyrimidine derivative 6g was the most potent compound of the series as an antiproliferative agent, with half-maximal inhibitory concentration (IC50) values in the single- or double-digit nanomolar range. Compound 6g bound to tubulin in the colchicine site and inhibited tubulin assembly with an IC50 value of 0.71 μM, and 6g inhibited EGFR activity with an IC50 value of 30 nM. Our data suggested that the excellent in vitro and in vivo profile of 6g may be derived from its dual inhibition of tubulin polymerization and EGFR kinase.
Benzamidobenzoic acids as potent PqsD inhibitors for the treatment of Pseudomonas aeruginosa infections
Hinsberger, Stefan,De Jong, Johannes C.,Groh, Matthias,Haupenthal, J?rg,Hartmann, Rolf W.
, p. 343 - 351 (2014/03/21)
Targeting PqsD is a promising novel approach to disrupt bacterial cell-to-cell-communication in Pseudomonas aeruginosa. In search of selective PqsD inhibitors, two series of benzamidobenzoic acids - one published as RNAP inhibitors and the other as PqsD inhibitors - were investigated for inhibitory activity toward the respective other enzyme. Additionally, novel derivatives were synthesized and biologically evaluated. By this means, the structural features needed for benzamidobenzoic acids to be potent and, most notably, selective PqsD inhibitors were identified. The most interesting compound of this study was the 3-Cl substituted compound 5 which strongly inhibits PqsD (IC 50 6.2 μM) while exhibiting no inhibition of RNAP.
