3-(tert-butyl)-1-cyclohexyl-1-(6-((2R,3R,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl)hexyl)urea | 1447464-73-4

• 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: 3-(tert-butyl)-1-cyclohexyl-1-(6-((2R,3R,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl)hexyl)urea
• 英文别名: IHVR-19029；3-tert-butyl-1-cyclohexyl-1-[6-[(2R,3R,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]hexyl]urea
• CAS: 1447464-73-4
• 化学式: C₂₃H₄₅N₃O₅
• 分子量: 443.627
• InChiKey: GFBNIASMQRMEDU-PLACYPQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.45
• 重原子数：
  31.0
• 可旋转键数：
  9.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  116.5
• 氢给体数：
  5.0
• 氢受体数：
  6.0

制备方法与用途

IHVR-19029是一种新型抗病毒化合物，可作为ERα-葡萄糖苷酶抑制剂，能够协同抑制黄热病和埃博拉病毒在培养细胞中的复制，并显著提高感染动物（尤其是小鼠）的存活率。

反应信息

• 作为反应物：
  描述：

  3-(tert-butyl)-1-cyclohexyl-1-(6-((2R,3R,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl)hexyl)urea 、 乙酸酐 在 吡啶 作用下， 以84%的产率得到(2R,3R,4R,5S)-2-(acetoxymethyl)-1-(6-(N-cyclohexylpivalamido) hexyl)piperidine-3,4,5-triyl triacetate
  参考文献：
  名称：

  IHVR-19029的酯类前药具有增强的口服暴露能力和胃肠道葡萄糖苷酶相互作用的预防作用。

  摘要：

  IHVR-19029（6）是内质网中主要的α-葡萄糖苷酶I和II抑制剂，可通过注射途径有效保护小鼠免受致命的埃博拉病毒和马尔堡病毒感染，但口服时生物利用度低且与肠道葡萄糖苷酶脱靶相互作用。为了提高有效的暴露水平并避免副作用，我们设计并合成了酯类前药。前药不仅在模拟的胃液和肠液中稳定，并且对葡糖苷酶无活性，而且在基于细胞的测定中还表现出抗登革热病毒感染的抗病毒活性。进一步的体外评估表明，前药的生物转化是物种依赖性的：在小鼠中，前药在血浆和肝脏中转化为6；在小鼠中，前药在血浆和肝脏中转化为6。而在人类中，转化主要发生在肝脏中。

  DOI：

  10.1021/acsmedchemlett.6b00332
• 作为产物：
  描述：

  (6-溴己氧基)-叔丁基二甲基硅烷 在 palladium on activated charcoal 、 四丁基氟化铵 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 乙腈 为溶剂， 生成 3-(tert-butyl)-1-cyclohexyl-1-(6-((2R,3R,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl)hexyl)urea
  参考文献：
  名称：

  Design and synthesis of N-alkyldeoxynojirimycin derivatives with improved metabolic stability as inhibitors of BVDV and Tacaribe virus

  摘要：

  Novel N-alkyldeoxynojirimycins (NADNJs) based on our previous lead 3 were designed, synthesized and tested in metabolic assays and in virus cultures. NADNJs containing terminal tertiary benzamide, sulfonamide, urea, and oxazolidinone moieties were discovered to have improved metabolic stability compared to 3, while maintaining submicromolar EC50 against BVDV and Tacaribe virus; and low cytotoxicity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.04.052

文献信息

• [EN] NOVEL ALKYLATED IMINO SUGARS EXHIBITING GLUCOSIDASE INHIBITION AND THEIR METHOD OF USE<br/>[FR] NOUVEAU IMINO SUCRES ALKYLÉS PRÉSENTANT UNE INHIBITION DE LA GLUCOSIDASE ET LEUR PROCÉDÉ D'UTILISATION
  申请人：INST HEPATITIS & VIRUS RES

  公开号：WO2013148791A1

  公开（公告）日：2013-10-03

  Pharmaceutical compositions of the invention comprise alkylated imino sugars derivatives having a disease-modifying action in the treatment of diseases associated with glucosidase activity that include viral hemorrhagic fevers, and any other diseases involving glucosidase activity. The present invention also relates to a method for treating or preventing diseases that involve infection with viral hemorrhagic fever (VHFs) viruses, including, for example, infection with arenaviruses, filoviruses, bunyaviruses, and flaviviruses, said method comprising administering to a subject an effective amount of a compound or composition according to the present invention.

  本发明的药物组合物包括烷基化亚胺糖衍生物，具有治疗与葡萄糖苷酶活性相关疾病的疾病修饰作用，包括病毒性出血热等与葡萄糖苷酶活性有关的疾病。本发明还涉及一种用于治疗或预防涉及感染病毒性出血热（VHFs）病毒的疾病的方法，例如与病原体感染有关的疾病，包括病毒性出血热、丝状病毒、布尼亚病毒和黄病毒感染，所述方法包括向受试者投予根据本发明的化合物或组合物的有效量。
• Novel Alkylated Imino Sugars Exhibiting Glucosidase Inhibition and Their Method of Use
  申请人：Baruch S. Bulumberg Institute

  公开号：US20150119366A1

  公开（公告）日：2015-04-30

  Pharmaceutical compositions of the invention comprise alkylated imino sugars derivatives having a disease-modifying action in the treatment of diseases associated with glucosidase activity that include Viral hemorrhagic fevers, and any other diseases involving glucosidase activity.

  本发明的制药组合物包括烷基化的亚胺糖衍生物，具有改变疾病进程的作用，用于治疗与葡萄糖苷酶活性相关的疾病，包括病毒性出血热和其他涉及葡萄糖苷酶活性的疾病。
• Alkylated imino sugars exhibiting glucosidase inhibition and their method of use
  申请人：Baruch S. Blumberg Institute

  公开号：US10376502B2

  公开（公告）日：2019-08-13

  Pharmaceutical compositions of the invention comprise alkylated imino sugars derivatives having a disease-modifying action in the treatment of diseases associated with glucosidase activity that include Viral hemorrhagic fevers, and any other diseases involving glucosidase activity.

  本发明的药物组合物包括在治疗与葡萄糖苷酶活性相关的疾病（包括病毒性出血热和其他任何涉及葡萄糖苷酶活性的疾病）时具有疾病调节作用的烷基化亚氨基糖衍生物。
• US9126937B2
  申请人：——

  公开号：US9126937B2

  公开（公告）日：2015-09-08
• Design and synthesis of N-alkyldeoxynojirimycin derivatives with improved metabolic stability as inhibitors of BVDV and Tacaribe virus
  作者：Yanming Du、Hong Ye、Fang Guo、Lijuan Wang、Tina Gill、Noshena Khan、Andrea Cuconati、Ju-Tao Guo、Timothy M. Block、Jinhong Chang、Xiaodong Xu

  DOI：10.1016/j.bmcl.2013.04.052

  日期：2013.7

  Novel N-alkyldeoxynojirimycins (NADNJs) based on our previous lead 3 were designed, synthesized and tested in metabolic assays and in virus cultures. NADNJs containing terminal tertiary benzamide, sulfonamide, urea, and oxazolidinone moieties were discovered to have improved metabolic stability compared to 3, while maintaining submicromolar EC50 against BVDV and Tacaribe virus; and low cytotoxicity. (C) 2013 Elsevier Ltd. All rights reserved.