- Discovery of selective HDAC/BRD4 dual inhibitors as epigenetic probes
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According to the binding mode of ABBV-744 with bromodomains and the cape space of HDAC, the novel selective HDAC/BRD4 dual inhibitors were designed and synthesized by the pharmacophore fusion strategy. Evaluating the biomolecular activities through SARs exploration identified three kinds of selective dual inhibitors 41c (HDAC1/BRD4), 43a (pan-HDAC/BRD4) and 43d (HDAC6/BRD4(BD2)), whose target-related cellular activities in MV-4-11 cells were also confirmed. Significantly, the selective dual inhibitor 41c (HDAC1/BRD4) exhibited synergistic effects against MV-4-11 cells, which strongly induced G0/G1 cell cycle arrest and apoptosis, and the first HDAC6/BRD4(BD2) dual inhibitor was found. This study provides support for selective HDAC/BRD4 dual inhibitors as epigenetic probes based on pyrrolopyridone core for the future biological evaluation in different cancer cell lines.
- Chen, Jingjing,Li, Yalei,Zhang, Jie,Zhang, Minmin,Wei, Aihuan,Liu, Hongchun,Xie, Zhicheng,Ren, Wenming,Duan, Wenwen,Zhang, Zhuo,Shen, Aijun,Hu, Youhong
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supporting information
(2020/10/20)
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- S1P1 AGONIST AND APPLICATION THEREOF
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The present invention relates to a class of tricyclic compounds and an application thereof as a sphingosine 1-phosphate type 1 (S1P1) receptor agonist. The invention specifically relates to a compound represented by formula (II), and a tautomer and pharmaceutically acceptable salt of same.
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Paragraph 0355-0358
(2021/10/02)
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- SPIRO COMPOUND AND USE THEREOF
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The present disclosure relates to a series of tricyclic compounds and the use thereof as receptor agonists of sphingosine-1-phosphate subtype 1 (S1P1), and in particular relates to compounds as shown in formula (I) or pharmaceutically acceptable salts the
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Paragraph 0273-0276
(2020/02/27)
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- OXADIAZOLE SUBSTITUTED INDAZOLE DERIVATIVES FOR USE AS SPHINGOSINE 1-PHOSPHATE 1 (S1P1) RECEPTOR AGONISTS
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Oxadiazole substituted indazole derivatives of formula (I) or pharmaceutical salts thereof having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their uses in the treatment of various disorders mediated by S1P1 receptors are disclosed.
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- OXADIAZOLE SUBSTITUTED INDAZOLE DERIVATIVES FOR USE AS SPHINGOSINE 1-PHOSPHATE 1 (S1P1) RECEPTOR AGONISTS
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Oxadiazole substituted indazole derivatives of formula (I) or pharmaceutical salts thereof having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their uses in the treatment of various disorders mediated by S1P1 receptor are disclosed.
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- AMINOPHENYLPROPANOIC ACID DERIVATIVE
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A compound represented by the formula (1): wherein each symbol is as defined in the specification, and a salt thereof and a prodrug thereof unexpectedly have superior GPR40 receptor agonist activity, superior in the properties as a pharmaceutical product such as stability and the like, and can be a safe and useful pharmaceutical agent as a drug for the prophylaxis or treatment of GPR40 receptor related pathology or diseases such as diabetes and the like.
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- (3,4-DISUBSTITUTED)PROPANOIC CARBOXYLATES AS S1P (EDG) RECEPTOR AGONISTS
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The present invention encompasses compounds of Formula A: A as well as the pharmaceutically acceptable salts thereof. The compounds are S1P1/Edg1 receptor agonists and thus have immunosuppressive, anti-inflammatory and hemostatic activities by modulating leukocyte trafficking, sequestering lymphocytes in secondary lymphoid tissues, and enhancing vascular integrity. The invention is also directed to pharmaceutical compositions containing such compounds and methods of treatment or prevention.
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Page/Page column 46
(2008/06/13)
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- 3-(4-BENZYLOXYPHENYL)PROPANOIC ACID DERIVATIVES
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The present invention provides a novel compound represented by the formula (I) wherein each symbol is as defined in the specification, a salt thereof and a prodrug thereof having a superior GPR40 receptor function modulating action, which can be used as an insulin secretagogue, an agent for the prophylaxis or treatment of diabetes and the like. They unexpectedly show superior GPR40 receptor agonist activity, and also show superior properties as a pharmaceutical product, such as stability and the like. Thus, they can be safe and useful pharmaceutical agents for the prophylaxis or treatment of GPR40 receptor related diseases in mammals.
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Page/Page column 91-92
(2010/02/12)
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- Tetrahydronaphthyridinyl-carboxamides having anti-convulsant activity
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Compounds of formula (I) and pharmaceutically acceptable salts and solvates: where R1is hydrogen, C1-6alkyl (optionally substituted by hydroxy or C1-4alkoxy), phenyl-C1-4alkyl-, C1-6alkenyl, C1-6
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- Substituted isoquinoline derivatives and their use as anticonvulsivants
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This invention relates to novel substituted isoquinoline derivatives and their use as anticonvulsants.
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