35970-78-6Relevant articles and documents
The Discovery and Development of Thienopyrimidines as Inhibitors of Helicobacter pylori That Act through Inhibition of the Respiratory Complex i
Mugengana, Alex K.,Vita, Nicole A.,Brown Gandt, Autumn,Moran, Kevin,Agyapong, George,Sharma, Lalit K.,Griffith, Elizabeth C.,Liu, Jiuyu,Yang, Lei,Gavrish, Ekaterina,Hevener, Kirk E.,Lafleur, Michael D.,Lee, Richard E.
, p. 1044 - 1058 (2021/02/09)
The successful treatment of Helicobacter pylori infections is becoming increasingly difficult due to the rise of resistance against current broad spectrum triple therapy regimens. In the search for narrow-spectrum agents against H. pylori, a high-throughp
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.
Route selection in the synthesis of C-4 and C-6 substituted thienopyrimidines
Bugge, Steffen,Kaspersen, Svein Jacob,Sundby, Eirik,Hoff, B?rd Helge
, p. 9226 - 9233 (2012/11/07)
Three different routes have been investigated for the preparation of 6-aryl-N-(1-arylethyl)thienopyrimidin-4-amines. First the possibilities of selective Suzuki reactions on 6-bromo-4-chlorothienopyrimidine were investigated. The preference for mono arylation at C-6 could be increased, in the case of Pd(PPh3)4 catalysis, by reducing the water content of the reaction, or by using less electron rich Pd-ligands. The highest selectivity was obtained with Pd(OAc)2 or Pd2(dba) 3, while reactions with the more electron rich Pd(PPh 3)4 and especially XPhos gave a lower mono- to dicoupled product ratio. Secondly, two alternative strategies avoiding this selectivity issue were tested. Suzuki reaction on C-6 of 6-bromothienopyrimidin-4(3H)-one (three examples) proceeded in 70-89% yield using Pd(PPh3)4 in dioxane/water. Similar conditions on 4-amino-6-bromo-thienopyrimidine (eight examples) gave 67-95% yield. The reaction could be performed with boronic acids containing nonprotected phenolic groups in the ortho, meta and para positions. By prolonging the reaction time, coupling with sterically crowded arylboronic acids was also efficient. Diarylation of 6-bromo-4-chlorothienopyrimidine gave the corresponding 4,6-diarylated derivatives in 71-80% yield depending on the nature of the arylboronic acid.
