14698-76-1Relevant academic research and scientific papers
Efficient entry into medium-ring keto-lactones. The ruthenium tetraoxide-promoted oxidative cleavage of β-hydroxyethers
Ferraz, Helena M. C.,Longo Jr., Luiz S.
, p. 1337 - 1339 (2003)
(Matrix presented) A new use of ruthenium tetraoxide is reported. The catalytic oxidative cleavage of hexahydro-benzofuran-3a-ols led to nine-membered ring keto-lactones in moderate to good yields and high purity. The reaction is clean and easily performed using catalytic amounts of ruthenium trichloride and an excess of sodium periodate as a cooxidant.
Design, synthesis and biological evaluation of novel 1-methyl-3-oxo-2,3,5,6,7,8-hexahydroisoquinolins as potential 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
, p. 25967 - 25978 (2015/10/20)
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.
Total synthesis of (±)-chondrillin, (±)-plakorin, and related peroxy ketals. development of a general route to 3,6-dihydro-1,2-dioxin-3-ols
Snider, Barry B.,Shi, Zhongping
, p. 1790 - 1800 (2007/10/02)
Seven-step syntheses of the antitumor cyclic peroxy ketals la, 2a, chondrillin (Ib), and plakorin (2b) from (methoxymethoxy)benzene (8) have been achieved in 26-28% overall yields. The key step is the photooxygenation of enone 4 with a sun lamp using rose bengal lactone or CuSO4 as a sensitizer which gives a mixture of peroxy hemiketals 15 and 16 in 75-85% yields. Acetal formation in acidic methanol completes the syntheses of 1 and 2. The mechanism of photooxygenation was ascertained using 3-nonen-2-one (22) as a model for 4. Irradiation converts 22 to the cis-enone 23 which undergoes photoenolization to give 24. Dienol 24 undergoes a sensitized reaction with oxygen to give 29 and 30. The detailed mechanism of this last step is not known, although singlet oxygen is probably not involved. This reaction is general for any enone or enal which can undergo photoenolization to give a dienol. Peroxy hemiketals 33a, 41, and 43-46 were prepared in 30-80% yields. Peroxy ketals can be used for the synthesis of furans, diones, and pyridazines.
Cardiotonic Agents. 1-Methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinones and Related Compounds. Synthesis and Activity
Kaiho, Tatsuo,San-nohe, Kunio,Kajiya, Seitaro,Suzuki, Tsuneji,Otsuka, Kengo,et al.
, p. 351 - 357 (2007/10/02)
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.
