71870-93-4Relevant articles and documents
Mechanochemical Magnesium-Mediated Minisci C-H Alkylation of Pyrimidines with Alkyl Bromides and Chlorides
Wu, Chongyang,Ying, Tao,Yang, Xinjie,Su, Weike,Dushkin, Alexandr V.,Yu, Jingbo
supporting information, p. 6423 - 6428 (2021/08/30)
A novel method to synthesize 4-alkylpyrimidines by the mechanochemical magnesium-mediated Minisci reaction of pyrimidine derivatives and alkyl halides has been reported. The reaction process operates with a broad substrate scope and excellent regioselectivity under mild conditions with no requirement of transition-metal catalysts, solvents, and inert gas protection. The practicality of this protocol has been demonstrated by the up-scale synthesis, mechanochemical product derivatization, and antimalarial drug pyrimethamine preparation.
Molecular Oxygen-Mediated Minisci-Type Radical Alkylation of Heteroarenes with Boronic Acids
Zhang, Lizhi,Liu, Zhong-Quan
supporting information, p. 6594 - 6597 (2017/12/26)
The carbon-carbon bond formation via autoxidation of organoboronic acid using 1 atm of O2 is achieved in a simple, clean, and green fashion. The approach allows a technically facile and environmentally benign access to structurally diverse heteroaromatics with medicinally privileged scaffolds. The strategy also displays its practicality and sustainability in the resynthesis of marketed drugs Crestor and pyrimethamine.
Synthesis and biological evaluation of N3-alkyl-thienopyrimidin-4-ones as mGluR1 antagonists
Kim, Minjoo,Kim, Youngjae,Seo, Seon Hee,Baek, Du-Jong,Min, Sun-Joon,Keum, Gyochang,Choo, Hyunah
, p. 1439 - 1451 (2015/07/15)
Metabotropic glutamate receptor subtype 1 (mGluR1) is a potential target for the treatment of neuropathic pain, and there has been much effort to discover mGluR1 antagonists. In this study, a series of N3-alkyl-thienopyrimidin-4-ones were prepared by introducing various alkyl and aryl groups to the N3- and 7-positions of the thienopyrimidin-4-one core structure, respectively, and their inhibitory activities against mGluR1 were biologically evaluated. Structure-activity relationship study revealed that the trans-4-methylcyclohexyl, cycloheptyl, and cyclooctyl groups at N3-position, and 2-fluorophenyl group at 7-position were most effective in potentiating the inhibitory activity of the thienopyrimidin-4-one derivatives against mGluR1. Among the synthesized compounds, 3-cyclooctyl-7-phenylthienopyrimidin-4-one and 3-cycloheptyl-7-(2-fluorophenyl)thienopyrimidin-4-one exhibited the most potent inhibitory activities with IC50 values of 115 and 107 nM, respectively.
Novel thienopyrimidinones as mGluR1 antagonists
Kim, Youngjae,Kim, Jeeyeon,Kim, Sora,Ki, Yooran,Seo, Seon Hee,Tae, Jinsung,Ko, Min Kyung,Jang, Hyun-Seo,Lim, Eun Jeong,Song, Chiman,Cho, Yoonjeong,Koh, Hae-Young,Chong, Youhoon,Choo, Il Han,Keum, Gyochang,Min, Sun-Joon,Choo, Hyunah
, p. 629 - 637 (2014/09/17)
There has been much attention to discover mGluR1 antagonists for treating various central nervous system diseases such as seizures and neuropathic pain. Thienopyrimidinone derivatives were designed, synthesized, and biologically evaluated against mGluR1. Among the synthesized compounds, 3-(4-methoxyphenyl)- 7-(o-tolyl)thienopyrimidin-4-one 30 exhibited the most potent inhibitory activity with an IC50 value of 45 nM and good selectivity over mGluR5. Also, the selective mGluR1 antagonist 30 showed marginal hERG channel activity (IC50 = 9.87 μM), good profiles to CYP isozymes, and a good pharmacokinetic profile. Overall, the compound 30 was identified as a selective mGluR1 antagonist with a good pharmacokinetic profile, which is probably devoid of cardiac side effect and drug-drug interactions. Therefore, the compound 30 can be expected to be broadly used as mGluR1 antagonistic chemical probe in in vitro and in vivo study for investigating CNS diseases.
