675-09-2Relevant articles and documents
A novel synthesis of 4,6-dimethyl-2-pyrone from carbon dioxide and mesityl oxide in the presence of an ethylzinc carbamate
Zhou, Ming,Yoshida, Yasuhiko,Ishii, Shigeru,Noguchi, Hiromichi
, p. 2241 - 2247 (1999)
The title synthesis, the first example of the CO2 fixation by use of an α,β-unsaturated ketone, has been successfully carried out, most preferably in triethylamine or pyridine at 120-160°C in the presence of ethylzinc diphenylcarbamate.
Development of Novel N-hydroxypyridone Derivatives as Potential Anti-Ischemic Stroke Agents
Hu, Linghao,Feng, Hongxuan,Zhang, Hongguang,Yu, Songda,Zhao, Qinyuan,Wang, Wei,Bao, Fengxia,Ding, Xun,Hu, Jiajing,Wang, Manjiong,Xu, Yixiang,Wu, Zengrui,Li, Xiaokang,Tang, Yun,Mao, Fei,Chen, Xiaoyan,Zhang, Haiyan,Li, Jian
supporting information, p. 1051 - 1067 (2020/03/10)
Our previous study had identified ciclopirox (CPX) as a promising lead compound for treatment of ischemic stroke. To find better neuroprotective agents, a series of N-hydroxypyridone derivatives based on CPX were designed, synthesized, and evaluated in this study. Among these derivatives, compound 11 exhibits significant neuroprotection against oxygen glucose deprivation and oxidative stress-induced injuries in neuronal cells. Moreover, compound 11 possesses good blood-brain barrier permeability and superior antioxidant capability. In addition, a complex of compound 11 with olamine-11·Ola possesses good water solubility, negligible hERG inhibition, and superior metabolic stability. The in vivo experiment demonstrates that 11·Ola significantly reduces brain infarction and alleviates neurological deficits in middle cerebral artery occlusion rats. Hence, compound 11·Ola is identified in our research as a prospective prototype in the innovation of stroke treatment.
Inhibition of cancer-associated mutant isocitrate dehydrogenases: Synthesis, structure-activity relationship, and selective antitumor activity
Liu, Zhen,Yao, Yuan,Kogiso, Mari,Zheng, Baisong,Deng, Lisheng,Qiu, Jihui J.,Dong, Shuo,Lv, Hua,Gallo, James M.,Li, Xiao-Nan,Song, Yongcheng
, p. 8307 - 8318 (2014/12/11)
Mutations of isocitrate dehydrogenase 1 (IDH1) are frequently found in certain cancers such as glioma. Different from the wild-type (WT) IDH1, the mutant enzymes catalyze the reduction of α-ketoglutaric acid to d-2-hydroxyglutaric acid (D2HG), leading to cancer initiation. Several 1-hydroxypyridin-2-one compounds were identified to be inhibitors of IDH1(R132H). A total of 61 derivatives were synthesized, and their structure-activity relationships were investigated. Potent IDH1(R132H) inhibitors were identified with Ki values as low as 140 nM, while they possess weak or no activity against WT IDH1. Activities of selected compounds against IDH1(R132C) were found to be correlated with their inhibitory activities against IDH1(R132H), as well as cellular production of D2HG, with R2 of 0.83 and 0.73, respectively. Several inhibitors were found to be permeable through the blood-brain barrier in a cell-based model assay and exhibit potent and selective activity (EC50 = 0.26-1.8 μM) against glioma cells with the IDH1 R132H mutation.
Two-stage synthesis of 3-(perfluoroalkyl)-substituted vinyldiazocarbonyl compounds and their nonfluorinated counterparts: A comparative study
Supurgibekov, Murat B.,Prakash, G.K. Surya,Nikolaev, Valerij A.
, p. 1215 - 1226 (2013/06/04)
Two approaches for the synthesis of fluorinated (F) and nonfluorinated (H) 4-(alkoxycarbonyl)-substituted cis- and trans-vinyldiazocarbonyl compounds with substituents of variable stereoelectronic nature (H, Me, Ph, CF3, OTBS) at the C-3 atom of the vinyl double bond from the relevant 1,3-dicarbonyl compounds were compared: a pathway using the Wittig reaction followed by a diazo transfer reaction was most efficient for the synthesis of the H-vinyldiazocarbonyl compounds (total yields of up to 60%), while the yields of their F-analogues under similar conditions did not exceed 16-37%. An approach via diazo transfer followed by the Wittig reaction, in contrast, is more effective for the preparation of F-vinyldiazocarbonyl compounds (total yields 37-69%). The configuration of the resulting F- and H-vinyldiazocarbonyl compounds is evidently controlled by the steric bulk of the substituent at the C-3 atom of the vinyl double bond and, in addition, depends on the specific synthetic pathway. Georg Thieme Verlag Stuttgart . New York.
