- Design, synthesis and biological evaluation of novel 1-methyl-3-oxo-2,3,5,6,7,8-hexahydroisoquinolins as potential EZH2 inhibitors
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The histone lysine methyltransferase EZH2 has been implicated as a key component in cancer aggressiveness, metastasis and poor prognosis. This study discovered a new class of hexahydroisoquinolin derivatives as EZH2 inhibitors. A structure-activity relationship study showed that the steric hindrance was important to the activity for EZH2. A preliminary optimization study led to the discovery of several potent compounds with low nanomolar to sub-nanomolar potency for EZH2. Biological evaluation indicated that SKLB1049 was a highly potent with improved solubility compared to EPZ6438, SAM-competitive, and cell-active EZH2 inhibitor that decreased global H3K27me3 in SU-DHL-6 and Pfeiffer lymphoma cells in a concentration- and time-dependent manner. Further study indicated that SKLB1049 caused cell arrest in G0/G1 phase. These compounds would be useful as chemical tools to further explore the biology of EZH2 and provided us with a start point to develop new EZH2 inhibitors.
- Zhang, Lidan,Song, Xuejiao,Wang, Ningyu,Zhao, Lifeng,Feng, Qiang,You, Xinyu,Peng, Cuiting,Gao, Tiantao,Xiong, Menghua,He, Bing,Gao, Chao,Luo, Yong,Xu, Ying,Zhang, Qiyi,Yu, Luoting
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p. 25967 - 25978
(2015/10/20)
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- NEW BICYCLIC DIOXANES, THEIR PREPARATION AND THEIR USE AS FRAGRANT COMPOUNDS
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The invention is directed to the use of compounds of formula (I), as fragrant agents. In this formula: - R3 and R4 are independently a hydrogen atom, a C1-C6 alkyl group or a C2-C6 alkenyl group, R5 is a C1-C6 alkyl group, a C2-C6 alkenyl group or a (CH2)0-2-aryl group, R6 is a C1 -C6 alkyl group, a C2-C6 alkenyl group, a (CH2)0-2-aryl group or a C5- C6 cycloalkyl or cycloalkenyl group, and R7 is a hydrogen atom, a C1-C6 alkyl group or a C2-C6 alkenyl group; or R3, R4 and R5 are as above defined, and R6 and R7 together with the carbon atom to which they are attached form a C5-C6 cycloalkyl or cycloalkenyl group.
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Page/Page column 11
(2011/02/24)
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- New bicyclic dioxanes, their preparation and their use as organoleptic compounds
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The present invention relates to novel 1,3-dioxane derivatives of formula (I) wherein each of R1 and R2 is a hydrogen atom, R3 and R4 are independently a hydrogen atom, a linear or branched C1-C6 alkyl group, or a linear or branched C2-C6 alkenyl group, and R5 is a linear or branched C1-C6 alkyl group, a linear or branched C2-C6 alkenyl group or a (CH2)0-2 - aryl group, and R6 and R7 are independently a hydrogen atom, a linear or branched C1-C6 alkyl group, a linear or branched C2-C6 alkenyl group or a (CH2)0-2 - aryl group, or R6 and R7 together with the carbon atom to which they are attached form a C5-C6 cycloalkyl group or a C5-C6 cycloalkenyl group, substituted or not; their preparation and their use as organoleptic compounds.
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Page/Page column 9
(2011/04/14)
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- Evaluation of TCS/ZnCl2 with acetic anhydride as an acetylating reagent for methylene ketones
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A new route for the preparation of β-diketones which have applications in organic synthesis by the reaction of methylene ketones, acetic anhydride, TCS and ZnCl2 in the solvent methylene chloride at room temperature produces the corresponding β-diketones in excellent yield. Copyright Taylor & Francis Inc.
- Elmorsy, Saad S.,Badawy, Doria S.,Khatab, Tamer K.
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p. 109 - 116
(2007/10/03)
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- Cardiotonic Agents. 1-Methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinones and Related Compounds. Synthesis and Activity
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A series of 1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinones and related compounds were synthesized and evaluated for positive inotropic activity.Most members of this series exerted a dose-dependent increase in myocardial contractility in the dog acute heart failure model, whereas they caused only slight changes in heart rate and blood pressure.Several derivatives, especially those with cyano, acetyl, and ethyl substituents at the 4-position, were more potent than milrinone, which was used as a reference. 4-Acetyl-1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinone (MS-857) is one of the most potent positive inotropic agents in this series.
- Kaiho, Tatsuo,San-nohe, Kunio,Kajiya, Seitaro,Suzuki, Tsuneji,Otsuka, Kengo,et al.
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p. 351 - 357
(2007/10/02)
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