Carbamic acid,[2-[trans-4-[(4-hydroxy-1-piperidinyl)carbonyl]cyclohexyl]ethyl]methyl-,4-chlorophenyl ester | 824430-09-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: Carbamic acid,[2-[trans-4-[(4-hydroxy-1-piperidinyl)carbonyl]cyclohexyl]ethyl]methyl-,4-chlorophenyl ester
• 英文别名: trans-{2-[4-(4-hydroxy-piperidine-1-carbonyl)cyclohexyl]ethyl}methylcarbamic acid 4-chloro phenyl ester
• CAS: 824430-09-3
• 化学式: C₂₂H₃₁ClN₂O₄
• 分子量: 422.952
• InChiKey: PAHWPIPXJDOVHD-QAQDUYKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.95
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  70.08
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  Cyclohexanecarboxylic acid,4-[2-[[(4-chlorophenoxy)carbonyl]methylamino]ethyl]-, trans- 、 4-羟基哌啶 、 Carbamic acid,[2-[trans-4-[(4-hydroxy-1-piperidinyl)carbonyl]cyclohexyl]ethyl]methyl-,4-chlorophenyl ester 生成
  参考文献：
  名称：

  Hydroxyalkylamide derivatives

  摘要：

  本发明涉及式(I)化合物，其中R1、R2、R3、R4、X、W、m和n如上所定义。所述化合物可用于治疗和/或预防与2,3-氧化齐墩果烷-鲨烯环化酶相关的疾病，例如高胆固醇血症、高脂血症、动脉硬化、血管疾病、真菌感染、寄生虫感染、胆结石、肿瘤和/或增生性疾病，以及治疗和/或预防糖耐量受损和糖尿病。

  公开号：

  US20050009906A1
• 作为产物：
  描述：

  2-((1r,4r)-4-(((tert-butyldimethylsilyl)oxy)methyl)cyclohexyl)acetonitrile 在 吡啶 、 盐酸 、 platinum(IV) oxide 、 sodium periodate 、 草酰氯 、 ruthenium(III) chloride monohydrate 、 氢气 、 sodium hydride 、 potassium carbonate 、 三乙胺 、 N,N-二甲基甲酰胺 、 六甲基二硅氮烷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 四氯化碳 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 50.17h， 生成 Carbamic acid,[2-[trans-4-[(4-hydroxy-1-piperidinyl)carbonyl]cyclohexyl]ethyl]methyl-,4-chlorophenyl ester
  参考文献：
  名称：

  Cytotoxic Effects of Combination of Oxidosqualene Cyclase Inhibitors with Atorvastatin in Human Cancer Cells

  摘要：

  Ten oxidosqualene c-yclase inhibitors with high efficacy as cholesterol-lowering agents and of different chemical structure classes were evaluated as potential anticancer agents against human cancer cells from various tissue origins and nontumoral human-brain-derived endothelial cells. Inhibition of cancer cell growth was demonstrated at micromolar concentrations, comparable to the concentrations of statins necessary for antitumor effect. Human glioblastoma cells were among the most sensitive cells. These compounds were also able to decrease the proliferation of angiogenic brain-derived endothelial cells, as a model of tumor-induced neovasculation. Additive effects in human glioblastoma cells were also demonstrated for oxidosqualene cyclase inhibitors in combination with atorvastatin while maintaining selectivity against endothelial cells. Thus, not only statins targeting the 3-hydroxy-3-methylglutaryl coenzyme A reductase but also inhibitors of oxidosqualene cyclase decrease tumor growth, suggesting new therapeutic opportunities of combined anti-cholesterol agents for dual treatment of glioblastoma.

  DOI：

  10.1021/jm300256z

文献信息

• US6965048B2
  申请人：——

  公开号：US6965048B2

  公开（公告）日：2005-11-15
• Hydroxyalkylamide derivatives
  申请人：Ackermann Jean

  公开号：US20050009906A1

  公开（公告）日：2005-01-13

  The present invention relates to compounds of formula (I) wherein R 1 , R 2 , R 3 , R 4 , X, W, m and n are as defined hereinabove. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with 2,3-oxidosqualane-lanosterol cyclase such as hypercholesterolemia, hyperlipemia, arteriosclerosis, vascular diseases, mycoses, parasite infections, gallstones, tumors and/or hyperproliferative disorders, and treatment and/or prophylaxis of impaired glucose tolerance and diabetes.

  本发明涉及以下式（I）的化合物 其中R 1 ，R 2 ，R 3 ，R 4 ，X，W，m和n如上所定义。这些化合物可用于治疗和/或预防与2,3-氧化齐墩果烷-鲁米叶酯环化酶相关的疾病，如高胆固醇血症、高脂血症、动脉硬化、血管疾病、真菌病、寄生虫感染、胆结石、肿瘤和/或过度增生性疾病，以及治疗和/或预防糖耐量受损和糖尿病。
• Cytotoxic Effects of Combination of Oxidosqualene Cyclase Inhibitors with Atorvastatin in Human Cancer Cells
  作者：Davide Staedler、Catherine Chapuis-Bernasconi、Henrietta Dehmlow、Holger Fischer、Lucienne Juillerat-Jeanneret、Johannes D. Aebi

  DOI：10.1021/jm300256z

  日期：2012.6.14

  Ten oxidosqualene c-yclase inhibitors with high efficacy as cholesterol-lowering agents and of different chemical structure classes were evaluated as potential anticancer agents against human cancer cells from various tissue origins and nontumoral human-brain-derived endothelial cells. Inhibition of cancer cell growth was demonstrated at micromolar concentrations, comparable to the concentrations of statins necessary for antitumor effect. Human glioblastoma cells were among the most sensitive cells. These compounds were also able to decrease the proliferation of angiogenic brain-derived endothelial cells, as a model of tumor-induced neovasculation. Additive effects in human glioblastoma cells were also demonstrated for oxidosqualene cyclase inhibitors in combination with atorvastatin while maintaining selectivity against endothelial cells. Thus, not only statins targeting the 3-hydroxy-3-methylglutaryl coenzyme A reductase but also inhibitors of oxidosqualene cyclase decrease tumor growth, suggesting new therapeutic opportunities of combined anti-cholesterol agents for dual treatment of glioblastoma.