15969-46-7Relevant articles and documents
2,4,6-Trisubstituted pyrimidines as a new class of selective adenosine A1 receptor antagonists
Chang, Lisa C. W.,Spanjersberg, Ronald F.,Von Frijtag Drabbe Künzel, Jacobien K.,Mulder-Krieger, Thea,Van Den Hout, Gijs,Beukers, Margot W.,Brussee, Johannes,IJzerman, Adriaan P.
, p. 6529 - 6540 (2004)
Adenosine receptor antagonists usually possess a bi- or tricyclic heteroaromatic structure at their core with varying substitution patterns to achieve selectivity and/or greater affinity. Taking into account molecular modeling results from a series of pot
Synthesis and biological evaluation of novel sigma-1 receptor antagonists based on pyrimidine scaffold as agents for treating neuropathic pain
Lan, Yu,Chen, Yin,Cao, Xudong,Zhang, Juecheng,Wang, Jie,Xu, Xiangqing,Qiu, Yinli,Zhang, Tan,Liu, Xin,Liu, Bi-Feng,Zhang, Guisen
, p. 10404 - 10423 (2015/02/19)
The discovery and synthesis of a new series of pyrimidines as potent sigma-1 receptor (σ1R) antagonists, associated with pharmacological antineuropathic pain activity, are the focus of this article. The new compounds were evaluated in vitro in σ-1 and σ-2 receptor binding assays. The nature of the pyrimidine scaffold was crucial for activity, and a basic amine was shown to be necessary according to the known pharmacophoric model. The most promising derivative was 5-chloro-2-(4-chlorophenyl)-4-methyl-6-(3-(piperidin-1-yl)propoxy)pyrimidine (137), which exhibited a high binding affinity to σ1R receptor (Ki σ1 = 1.06 nM) and good σ-1/2 selectivity (1344-fold). In in vivo tests, compound 137 exerted dose-dependent antinociceptive effects in mice formalin model and rats CCI models of neuropathic pain. In addition, no motor impairments were found in rotarod tests; acceptable pharmacokinetic properties were also noted. These data suggest compound 137 may constitute a novel class of drugs for the treatment of neuropathic pain.
A metal-free tandem approach to prepare structurally diverse N-heterocycles: Synthesis of 1,2,4-oxadiazoles and pyrimidinones
Gupta, Puneet K.,Hussain, Mohd. Kamil,Asad, Mohd.,Kant, Ruchir,Mahar, Rohit,Shukla, Sanjeev K.,Hajela, Kanchan
, p. 3062 - 3070 (2014/07/07)
A metal-free one-pot approach to the diversity oriented synthesis of N-heterocycles, 1,2,4-oxadiazoles and 2,6 disubstituted pyrimidin-4-ones is described via carboxamidation of amidines with aryl carboxylic acids and aryl propargylic acids. The reactions occur at room temperature forming N-acylamidines which undergo tandem nucleophilic addition-deamination- intramolecular cyclisation to give the corresponding heterocyclic compounds in good to excellent yields. This one pot approach has led to the successful synthesis of the drug lead molecule, ataluren, 3-(5-(2-fluorophenyl)-1,2,4- oxadiazol-3-yl) benzoic acid in two steps. the Partner Organisations 2014.
