trans-(4-formylcyclohexyl)methylcarbamic acid tert-butyl ester | 400898-94-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: trans-(4-formylcyclohexyl)methylcarbamic acid tert-butyl ester
• CAS: 400898-94-4
• 化学式: C₁₃H₂₃NO₃
• 分子量: 241.331
• InChiKey: UYNAFGOCUOKXDS-XYPYZODXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.61
• 重原子数：
  17.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  46.61
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  trans-(4-formylcyclohexyl)methylcarbamic acid tert-butyl ester 在 正丁基锂 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 18.83h， 生成 tert-butyl N-(trans-4-ethynylcyclohexyl)-N-methylcarbamate
  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
• 作为产物：
  描述：

  tert-butyl N-[4-[methoxy(methyl)carbamoyl]cyclohexyl]carbamate 在 lithium aluminium tetrahydride 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 trans-(4-formylcyclohexyl)methylcarbamic acid tert-butyl 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

• Oxidosqualene Cyclase (OSC) Inhibitors for the Treatment of Dyslipidemia
  作者：Henrietta Dehmlow、Ralf Thoma、Armin Ruf、Narendra Panday、Elisabeth Von Der Mark、Olivier Morand、Hans Peter Märki、Manfred Kansy、Peter Hartman、Philippe Coassolo、Alexander Chucholowski、Denise Blum-Kaelin、Johannes Aebi、Jean Ackermann、Tanja Schulz-Gasch

  DOI：10.2533/000942905777676858

  日期：——

  Novel inhibitors of oxidosqualene cyclase (OSC) for the treatment of dyslipidemia are reported. Starting point for the chemistry program was a set of compounds derived from a fungicide project which, in addition to high affinity for OSC from Candida albicans, also showed high affinity for the human enzyme (hOSC). Here the evaluation process of different scaffolds is outlined for two representative series, the phenyl substituted benzo[d]isothiazoles and the aminocyclohexanes. The most promising compounds derived from the latter series were further profiled in vivo and showed promising properties with respect to modulation of lipid parameters.

  报告了用于治疗血脂异常的新型氧化角鲨烯环氧化酶（OSC）抑制剂。化学项目的起点是一组来自杀菌剂项目的化合物，这些化合物除了对白念珠菌的OSC具有高亲和力外，对人类酶（hOSC）也显示出高亲和力。这里概述了两个代表性系列，即苯基取代的苯并[d]异噻唑和氨基环己烷的不同支架评估过程。从后者系列中得到的最有前途的化合物在体内进行了进一步研究，并显示出在调节脂质参数方面的前景性。

• 2,3-oxidosqualene-lanosterol cyclase inhibitors
  申请人：——

  公开号：US20020045777A1

  公开（公告）日：2002-04-18

  The present invention relates to aminocyclohexanol derivatives useful for the treatment and/or prophylaxis of diseases which are associated with 2,3-oxidosqualene-lanosterol cyclase such as hypercholesterolemia, hyperlipemia, arteriosclerosis, vascular diseases, mycoses, gallstones, tumors and/or hyperproliferative disorders, and treatment and/or prophylaxis of impaired glucose tolerance and diabetes.

  本发明涉及氨基环己醇衍生物，用于治疗和/或预防与2,3-氧化甾二烯-鲨烯合酶相关的疾病，如高胆固醇血症、高脂血症、动脉硬化、血管疾病、真菌病、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。
• Substituted cyclohexane derivatives
  申请人：——

  公开号：US20030186984A1

  公开（公告）日：2003-10-02

  The present invention relates to compounds of formula (I) 1 wherein A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , U, V, m, n and o are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with the 2,3-oxidosqualene-lanosterol cyclase biosynthetic pathway such as hypercholesterolemia and hyperlipemia.

  本发明涉及式(I)的化合物，其中A1、A2、A3、A4、A5、A6、U、V、m、n和o如规范中定义的那样，以及其药学上可接受的盐。这些化合物对于治疗和/或预防与2,3-氧化甾二烯-鲨烯合成途径相关的疾病，如高胆固醇血症和高脂血症，是有用的。
• 2,3-Oxidosqualene-lanosterol cyclase inhibitors
  申请人：Ackermann Jean

  公开号：US20050176766A1

  公开（公告）日：2005-08-11

  The present invention relates to aminocyclohexanol derivatives useful for the treatment and/or prophylaxis of diseases which are associated with 2,3-oxidosqualene-lanosterol cyclase such as hypercholesterolemia, hyperlipemia, arteriosclerosis, vascular diseases, mycoses, gallstones, tumors and/or hyperproliferative disorders, and treatment and/or prophylaxis of impaired glucose tolerance and diabetes.

  本发明涉及氨基环己醇衍生物，用于治疗和/或预防与2,3-氧化角鲨烯-鲨烯环化酶相关的疾病，如高胆固醇血症、高脂血症、动脉硬化、血管疾病、真菌感染、胆结石、肿瘤和/或过度增殖性疾病，以及治疗和/或预防糖耐量受损和糖尿病。
• 1,3-BENZODIOXOLE DERIVATIVE
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP3121175A1

  公开（公告）日：2017-01-25

  The present invention provides a compound having a particular chemical structure or a pharmacologically acceptable salt thereof which has an excellent inhibitory effect on EZH1 and/or EZH2 activity. The present invention provides a compound having a 1,3-benzodioxole structure represented by the general formula (I) or a pharmacologically acceptable salt thereof, or a pharmaceutical composition comprising the compound (wherein R1, R2, R3, R4, R5, R6, and V in the formula (I) are each as defined in the present specification).

  本发明提供了一种具有特定化学结构的化合物或其药理学上可接受的盐，该化合物对 EZH1 和/或 EZH2 的活性具有极佳的抑制作用。本发明提供了一种具有通式（I）所代表的 1，3-苯并二恶茂结构的化合物或其药理学上可接受的盐，或包含该化合物的药物组合物（其中式（I）中的 R1、R2、R3、R4、R5、R6 和 V 均如本说明书中所定义）。