- Synthesis and biological evaluation of N3-alkyl-thienopyrimidin-4-ones as mGluR1 antagonists
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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.
- Kim, Minjoo,Kim, Youngjae,Seo, Seon Hee,Baek, Du-Jong,Min, Sun-Joon,Keum, Gyochang,Choo, Hyunah
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p. 1439 - 1451
(2015/07/15)
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- Novel thienopyrimidinones as mGluR1 antagonists
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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.
- 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
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p. 629 - 637
(2014/09/17)
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- THIENOPYRIMIDINONE DERIVATIVES AS mGluR1 ANTAGONISTS
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Disclosed are thienopyrimidinone derivatives as antagonists that act on metabotropic glutamate receptor subtype 1. The thienopyrimidinone derivatives show pharmacological activity against metabotropic glutamate receptor-related diseases, including pain, such as neuropathic pain and migraine, psychiatric diseases, such as anxiety disorder and schizophrenia, urinary incontinence, and neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Also disclosed are methods for preparing the thienopyrimidinone derivatives, and pharmaceutical compositions containing the thienopyrimidinone derivatives as active ingredients.
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- Phase transfer catalysis assisted thorpe reaction for the synthesis of 3-aminothiophene-2-carboxylates
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Thorpe cyclization constructing synthetically important methyl or ethyl 3-amino-4-arylthiophene-2-carboxylates has been studied using eco friendly phase transfer catalysis technique. 3-Amino-4-arylthiophene-2-carboxylates have been synthesized from 3-hydr
- Shah
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experimental part
p. 368 - 372
(2012/02/04)
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- Design, synthesis and antiproliferative activity of tripentones: A new series of antitubulin agents
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Structure-activity relationship studies of a new series of tripentones (thieno[2,3-b]pyrrolizin-8-ones), led us to prepare several derivatives with antiproliferative activities. The most promising 3-(3-hydroxy-4-methoxyphenyl)thieno[2,3-b]pyrrolizin-8-one 20 (leukemia L1210, IC50 = 15 nM) was shown to be a potent inhibitor of tubulin polymerization.
- Lisowski, Vincent,Enguehard, Cecile,Lancelot, Jean-Charles,Caignard, Daniel-Henri,Lambel, Stephanie,Leonce, Stephane,Pierre, Alain,Atassi, Ghanem,Renard, Pierre,Rault, Sylvain
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p. 2205 - 2208
(2007/10/03)
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- Synthesis of thieno[3,2-d]pyrimidine-2,4-diones cyclic and acyclic nucleosides as potential anti HIV agents
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Synthesis of cyclic and acyclic nucleosides was achieved by alkylation of 7-methyl or arylthieno[3,2-d]pyrimidine-2,4-diones following the Vorbruggen and Niedballa's method [1]. After a possible deprotection, potential anti HIV agents were obtained.
- Jourdan,Laduree,Robba
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p. 305 - 312
(2007/10/02)
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- Antihypertensive thienopyridines
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Novel thienopyridones with antihypertensive activity have the formula I, STR1 wherein the ring A represents an optionally substituted thiophene ring; m is 0 or 1; n is 0, 1 or 2; R is lower alkyl and R1 is lower alkyl. The fused thieno-ring may
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- Synthese d'amino-3 thiophenes a partir d'aryl- et d'hetaryl-acetonitrile (1)
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Applying Fiesselman's condensation to α-hydroxymethylene nitriles the authors describe a synthesis of substituted aminothiophenes.
- Kirsch, G.,Cagniat, D.,Cagniat, P.
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p. 443 - 445
(2007/10/02)
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