- Binding pocket-based design, synthesis and biological evaluation of novel selective BRD4-BD1 inhibitors
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Bromodomain-containing protein 4 (BRD4), consisting of two tandem bromodomains (BD1 and BD2), is key epigenetic regulator in fibrosis and cancer, which has been reported that BD1 and BD2 have distinct roles in post-translational modification. But there ar
- Ma, Junlong,Chen, Heng,Yang, Jie,Yu, Zutao,Huang, Pan,Yang, Haofeng,Zheng, Bifeng,Liu, Rangru,Li, Qianbin,Hu, Gaoyun,Chen, Zhuo
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p. 1871 - 1881
(2019/03/27)
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- Novel heterocyclic compounds and organic light-emitting diode including the same
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The present invention relates to a heterocyclic compound represented by the following formula (A) or (B), and to an organic light-emitting diode including the same, wherein substituents Randprime;, RandPrime;, A1 to A4, L, W, Z and n are each as defined i
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Paragraph 0567-0570
(2018/04/14)
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- Substituted Nitrogen Heterocycles and Synthesis and Uses Thereof
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The invention relates to a nitrogen heterocycle compound of formula 1: Also disclosed are a method of synthesizing the compound and use of the compound for treating various diseases and conditions.
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Page/Page column 35-36
(2009/10/06)
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- THIENO-PYRIDINE DERIVATIVES AS GABA-B ALLOSTERIC ENHANCERS
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The present invention relates to compounds of formula (I), Wherein R1 to R5 are as defined in the specification which compounds are active on the GABABreceptor and can be used for the manufacture of medicaments useful for treating CNS disorders.
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Page/Page column 27
(2008/06/13)
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- 2-Amino-3-aroyl-4,5-alkylthiophenes: Agonist allosteric enhancers at human a1 adenosine receptors
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2-Amino-3-benzoylthiophenes are allosteric enhancers (AE) of agonist activity at the A1 adenosine receptor. The present report describes syntheses and assays of the AE activity at the human A1AR (hA1AR) of a panel of compounds consisting of nine 2-amino-3-aroylthiophenes (3a-i), eight 2-amino-3-benzoyl-4,5-dimethylthiophenes (12a-h), three 3-aroyl-2-carboxy-4,5-dimethylthiophenes (15a-c), 10 2-amino-3-benzoyl-5,6-dihydro-4H-cyclopenta[b]thiophenes (17a-j), 14 2-amino-3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophenes (18a-n), and 15 2-amino-3-benzoyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophenes (19a-o). An in vitro assay employing the A1AR agonist [125I]ABA and membranes from CHO-K1 cells stably expressing the hA1AR measured, as an index of AE activity, the ability of a candidate AE to stabilize the agonist-A1AR-G protein ternary complex. Compounds 3a-i had little or no AE activity, and compounds 12a-h had only modest activity, evidence that AE activity depended absolutely on the presence of at least a methyl group at C-4 and C-5. Compounds 17a-c lacked AE activity, suggesting the 2-amino group is essential. Polymethylene bridges linked thiophene C-4 and C-5 of compounds 17a-j, 18a-n, and 19a-o. AE activity increased with the size of the -(CH2)n- bridge, n = 3 1AR contains an allosteric binding site able to accommodate 3-aroyl substituents that are bulky and/or hydrophobic but not necessarily planar. A second region in the allosteric binding site interacts constructively with alkyl substituents at thiophene C-4 and/or C-5.
- Tranberg, C. Elisabet,Zickgraf, Andrea,Giunta, Brian N.,Luetjens, Henning,Figler, Heidi,Murphree, Lauren J.,Falke, Ruediger,Fleischer, Holger,Linden, Joel,Scammells, Peter J.,Olsson, Ray A.
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p. 382 - 389
(2007/10/03)
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- THIOPHENES USEFUL FOR MODULATING THE ADENOSINE RECEPTOR
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The present invention relates to compounds of formulas (IA), (IB), and (IC): STR1 the preparation thereof, pharmaceutical formulations thereof, and their use in medicine as allosteric adenosine receptor modulators for uses including protection against hypoxia and ischemia induced injury and treatment of adenosine-sensitive cardiac arrhythmias.
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- Allosteric modulation of the adenosine A1 receptor. Synthesis and biological evaluation of novel 2-amino-3-benzoylthiophenes as allosteric enhancers of agonist binding
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Novel allosteric enhancers of agonist binding to the rat adenosine A1 receptor are described. The lead compound for the new series was PD 81,723 ((2-amino-4,5-dimethyl-3-thienyl)[3-(trifluoromethyl)phenyl]methanone), a compound previously reported by Bruns and co-workers (Mol. Pharmacol. 1990, 38, 950-958). The 4,5-dimethyl group and the benzoyl moiety were targets for further modifications, leading to series of 4,5-dialkyl (12a-g), of tetrahydrobenzo (12h-u), and of tetrahydropyridine (13a-g) derivatives. A number of compounds, in particular 12b, 12e, 12j, 12n, and 12u, proved superior to PD 81,723. Their EC50 values for enhancing the binding of the adenosine A1 receptor agonist N6-cyclopentyladenosine to the receptor were lower, and/or their antagonistic activity on the adenosine A1 receptor was shown to be diminished.
- Van Der Klein, Pieter A. M.,Kourounakis, Angeliki P.,IJzerman, Ad P.
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p. 3629 - 3635
(2007/10/03)
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