- 2,4,6-Trisubstituted pyrimidines as a new class of selective adenosine A1 receptor antagonists
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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
- 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.
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Read Online
- ELECTROACTIVE MATERIALS
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There is disclosed a compound which is an N-heterocycle having at least one substituent of Formula (I), In Formula I: Q1, Q2, Q3, Q4, and Q5 are the same or different and can be N or CR1; R1 is the same or different at each occurrenc
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Page/Page column 66; 67
(2018/01/17)
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- Synthesis and biological evaluation of novel sigma-1 receptor antagonists based on pyrimidine scaffold as agents for treating neuropathic pain
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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.
- Lan, Yu,Chen, Yin,Cao, Xudong,Zhang, Juecheng,Wang, Jie,Xu, Xiangqing,Qiu, Yinli,Zhang, Tan,Liu, Xin,Liu, Bi-Feng,Zhang, Guisen
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p. 10404 - 10423
(2015/02/19)
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- A phosphine-catalyzed preparation of 4-Arylidene-5-imidazolones
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A simple and efficient method for constructing 4-arylidene-5-imidazolones was developed using a phosphinecatalyzed tandem umpolung addition and intramolecular cyclization of amidine pronucleophiles on arylpropiolates. The reaction offers a robust route to heterocycle analogues of the fluorescent protein chromophores. (Chemical Equation Presented).
- Gabillet, Sandra,Loreau, Olivier,Specklin, Simon,Rasalofonjatovo, Evelia,Taran, Frdric
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p. 9894 - 9898
(2015/01/09)
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- A metal-free tandem approach to prepare structurally diverse N-heterocycles: Synthesis of 1,2,4-oxadiazoles and pyrimidinones
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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.
- Gupta, Puneet K.,Hussain, Mohd. Kamil,Asad, Mohd.,Kant, Ruchir,Mahar, Rohit,Shukla, Sanjeev K.,Hajela, Kanchan
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p. 3062 - 3070
(2014/07/07)
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- Aminopyrimidinone Cdc7 Kinase Inhibitors
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We have investigated the SAR of a series of pyrimidinone-containing Cdc7 kinase inhibitors. A wide range of amine substitutions give potent compounds with activities (Ki) less than 1 nM. Kinase selectivity is reasonable and cytotoxicity corresponds to inhibition of MCM2 phosphorylation.
- Woods, Keith W.,Lai, Chunqiu,Miyashiro, Julie M.,Tong, Yunsong,Florjancic, Alan S.,Han, Edward K.,Soni, Niru,Shi, Yan,Lasko, Loren,Leverson, Joel D.,Johnson, Eric F.,Shoemaker, Alexander R.,Penning, Thomas D.
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p. 1940 - 1943
(2012/04/17)
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- A facile synthesis of pyrimidin-4-ones
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A facile synthesis of 2,6-disubstituted pyrimidin-4-ones and 2,5,6-trisubstituted pyrimidin-4-ones from commercially available materials with application of microwave technology in key steps is described.
- Guo, Cheng
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scheme or table
p. 548 - 549
(2010/10/02)
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- PYRIMIDINE SUBSTITUTED MACROCYCLIC HCV INHIBITORS
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Compounds of the Formula (I) including a stereoisomer thereof, or an N-oxide, a pharmaceutically acceptable addition salt, or a pharmaceutically acceptable addition solvate thereof; useful as HCV inhibitors; processes for preparing these compounds as well as pharmaceutical compositions comprising these compounds as active ingredient.
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Page/Page column 91-92
(2008/12/08)
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- A convenient synthesis of 5- and 6-substituted 2-phenyl-3H-pyrimidin-4-ones
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A simple and convenient one-pot procedure for the synthesis of 5- and 6-substituted 2-phenyl-3H-pyrimidin-4-ones by the condensation of 4-alkoxy-1,1,1-trichloroalk-3-en-2-ones with benzamidine hydrochloride is described. Georg Thieme Verlag Stuttgart.
- Zanatta, Nilo,Fantinel, Leonardo,Lourega, Rogerio V.,Bonacorso, Helio G.,Martins, Marcos A. P.
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p. 358 - 362
(2008/09/20)
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- NOVEL PYRIMIDINE COMPOUNDS, PROCESS FOR THEIR PREPARATION AND COMPOSITIONS CONTAINING THEM
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The present invention provides new heterocyclic compounds, particularly substituted pyrimidines, methods and compositions for making and using these heterocyclic compounds, and methods for treating a variety of diseases and disease states, including atherosclerosis, arthritis, restenosis, diabetic nephropathy, or dyslipidemia, or disease states mediated by the low expression of Perlecan.
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Page/Page column 257
(2008/06/13)
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- SUBSTITUTED PYRIMIDINES AS LIGANDS OF ADENOSINE RECEPTORS
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The invention provides a compound of formula (I) wherein R and R' are selected from hydrogen, alkyl, alkenyl, alkynyl, or aryl; R'' and R''' are selected from hydrogen, acyl, thio-acyl, seleno-acyl, alkyl, alkenyl, alkynyl, or aryl; or a pharmaceutically
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Page/Page column 24-25
(2008/06/13)
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- SYNTHESIS AND PROPERTIES OF PHENYL(METHYL)-SUBSTITUTED 2- AND 4-NITROSOPYRIMIDINES
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Phenyl(methyl)-substituted 2- and 4-nitroso- and azoxypyrimidines were synthesized for the first time by the oxidation of phenyl(methyl)-substituted 2- and 4-hydroxyaminopyrimidines by activated MnO2, Ag2CO3 on zeolite, or BaMnO4.Certain chemical properti
- Moskalenko, G. G.,Sedova, V. F.,Mamaev, V. P.
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p. 805 - 811
(2007/10/02)
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- OXIDATION OF HYDROXYAMINO- AND NITROSOPYRIMIDINES. SYNTHESIS OF 2- AND 4-NITROPYRIMIDINES
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Oxidation of phenyl- and methyl-substituted 2- and 4-hydroxyamino- and -nitrosopyrimidines has given the azoxy- and nitropyrimidines, respectively.The behavior of the nitropyrimidines obtained towards reduction and nucleophilic substitution is considered.
- Moskalenko, G. G.,Sedova, V. F.,Mamaev, V. P.
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p. 919 - 924
(2007/10/02)
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- SYNTHESIS OF SUBSTITUTED 2- AND 4-HYDROXYAMINOPYRIMIDINES
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The reaction of 2- and 4-chlorine-containing alkyl(aryl)pyrimidines with hydroxylamine was studied.It was shown that, depending on the amount of hydroxylamine , N,O-dipyrimidinylhydroxyamides or the corresponding 2- and 4-hydroxyaminopyrimidines are formed together with 2- and 4-oxodihydropyrimidines.
- Moskalenko, G. G.,Sedova, V. F..,Mamaev, V. P.
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p. 1232 - 1236
(2007/10/02)
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