hepta-2,6-dienoic acid methoxy-methylamide | 853645-31-5

• 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: hepta-2,6-dienoic acid methoxy-methylamide
• 英文别名: (2E)-N-methoxy-N-methylhepta-2,6-dienamide
• CAS: 853645-31-5
• 化学式: C₉H₁₅NO₂
• 分子量: 169.224
• InChiKey: XTEAQAGTNZKOKJ-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  hepta-2,6-dienoic acid methoxy-methylamide 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 12.17h， 生成 (9E,13E)-(R)-2,4-Bis-(tert-butyl-dimethyl-silanyloxy)-1-chloro-7-methyl-7,8,11,12-tetrahydro-16H-6-oxa-benzocyclotetradecene-5,15-dione
  参考文献：
  名称：

  Concise Synthesis of Pochonin A, an HSP90 Inhibitor

  摘要：

  [GRAPHICS]An expedient synthesis of (-)-pochonin A is reported (seven steps). This natural product is closely related to radicicol and was shown to be a 90 nM inhibitor of HSP90.

  DOI：

  10.1021/ol052263+
• 作为产物：
  描述：

  4-戊烯-1-醇 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 hepta-2,6-dienoic acid methoxy-methylamide
  参考文献：
  名称：

  通过基于 Julia 烯烃化方案的合成方便地获得 α,β-不饱和 N-甲氧基-N-甲基-酰胺官能团的新试剂

  摘要：

  开发了一种用于合成α,β-不饱和N-甲氧基-N-甲基-酰胺结构单元的新试剂。2-(苯并[d]噻唑-2-基磺酰基)-N-甲氧基-N-甲基乙酰胺，一种具有无限保质期的结晶固体，可以通过两个方便的步骤从 2-氯-N-甲氧基-N-轻松制备甲基乙酰胺，在 Julia 条件下与多种醛反应以提供 α,β-不饱和 N-甲氧基-N-甲基-酰胺官能团。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

  DOI：

  10.1002/ejoc.200600126

文献信息

• [EN] SYNTHESIS OF RESORCYLIC ACID LACTONES USEFUL AS THERAPEUTIC AGENTS<br/>[FR] SYNTHÈSE DE LACTONES D'ACIDE RÉSORCYLIQUE UTILES EN TANT QU'AGENTS THÉRAPEUTIQUES
  申请人：UNIV STRASBOURG

  公开号：WO2009091921A1

  公开（公告）日：2009-07-23

  Disclosed are macrocyclic compounds of formulae I, I', II, II', III, III', IV, and V, which are analogs of the pochonin resorcylic acid lactones, pharmaceutical compositions comprising the compounds, and methods and uses comprising the compounds for the treatment of diseases mediated by kinases and Heat Shock Protein 90 HSP90.

  公开的是式I、I'、II、II'、III、III'、IV和V的大环化合物，它们是pochonin resorcylic acid lactones的类似物，包括这些化合物的药物组合物，以及包括这些化合物用于治疗由激酶和热休克蛋白90 HSP90介导的疾病的方法和用途。
• Diversity-Oriented Synthesis of Pochonins and Biological Evaluation against a Panel of Kinases
  作者：Emilie Moulin、Sofia Barluenga、Frank Totzke、Nicolas Winssinger

  DOI：10.1002/chem.200600553

  日期：2006.11.24

  14-membered resorcylic acid lactones. As there are a high number of ATPase and kinase inhibitors among natural resorcylic lactones, a library based on the pochonin scaffold, with five points of diversity, was prepared which includes diversity beyond that of the natural analogues. The library was synthesized by using solid-supported reagents amenable to automation. Testing the library for its inhibition

  Pochonins AF最近被表征为自然存在的14元间苯二酸内酯家族的6个新成员。由于天然间苯二酚内酯中存在大量的ATPase和激酶抑制剂，因此建立了基于软骨素支架的文库，该文库具有五个多样性点，其中包括超出天然类似物的多样性。该文库是通过使用适合自动化的固体支持试剂合成的。测试该文库在10 microM下对一组24种激酶的抑制作用后，命中率> 14％。这些结果证明了间苯二酚对抑制治疗相关激酶的潜力。
• Macrocyclic compounds useful as inhibitors of kinases and HSP90
  申请人：Winssinger Nicolas

  公开号：US20080146545A1

  公开（公告）日：2008-06-19

  Disclosed are macrocyclic compounds of formulae I-V, which are analogs of the pochonin resorcylic acid lactones, and processes for the preparation of the compounds. The compounds disclosed are useful as inhibitors of kinases and Heat Shock Protein 90 (HSP 90). Also disclosed are pharmaceutical compositions comprising an effective kinase-inhibiting amount or an effective HSP90-inhibiting amount of the compounds and methods for the treatment of disorders that are mediated by kinases and HSP90.

  本发明公开了式I-V的大环化合物，它们是pochonin邻苯二酚内酯的类似物，并公开了制备这些化合物的方法。所公开的化合物可用作激酶和热休克蛋白90（HSP 90）的抑制剂。还公开了包含有效的激酶抑制剂量或有效的HSP90抑制剂量的药物组合物以及治疗由激酶和HSP90介导的疾病的方法。
• MACROCYCLIC COMPOUNDS USEFUL AS INHIBITORS OF KINASES AND HSP90
  申请人：WINSSINGER Nicolas

  公开号：US20120077775A1

  公开（公告）日：2012-03-29

  Disclosed are macrocyclic compounds of formulae I-V, which are analogs of the pochonin resorcylic acid lactones, and processes for the preparation of the compounds. The compounds disclosed are useful as inhibitors of kinases and Heat Shock Protein 90 (HSP 90). Also disclosed are pharmaceutical compositions comprising an effective kinase-inhibiting amount or an effective HSP90-inhibiting amount of the compounds and methods for the treatment of disorders that are mediated by kinases and HSP90.

  本发明公开了式I-V的大环化合物，它们是pochonin酚羧酸内酯的类似物，并公开了制备这些化合物的方法。所公开的化合物可用作激酶和热休克蛋白90（HSP90）的抑制剂。还公开了含有有效的激酶抑制剂量或有效的HSP90抑制剂量的药物组合物以及治疗由激酶和HSP90介导的疾病的方法。
• Treatment Of Neurofibromatosis With Radicicol And Its Derivatives
  申请人：CHEN Ruihong

  公开号：US20100292218A1

  公开（公告）日：2010-11-18

  The present invention provides compounds of formulae Ia, Ia′, IIa, IIa′, IIIa, IIIa′, IVa, or Va and the therapeutic use thereof. The present invention also includes methods of treating NF2-deficient or NF1-deficient cells or neurodegenerative diseases with radicicol or its derivatives, such as one or more compounds of formula I, II, III, IV, V, Ia, Ia′, IIa, IIa′, IIIa, IIIa′, IVa, or Va. Furthermore, the present invention is directed to methods of inhibiting the growth of NF2-deficient or NF1-deficient tumors. The methods comprise contacting NF2-deficient or NF1-deficient tumor cells with radicicol or its derivatives, such as one or more compounds of formula I, II, III, IV, V, Ia, Ia′, IIa, IIa′, IIIa, IIIa′, IVa, or Va. The present invention is also directed to the combinational use of radicicol or its derivatives, such as one or more compounds of formula I, II, III, IV, V, Ia, Ia′, IIa, IIa′, IIIa, IIIa′, IVa, or Va with at least one additional active agent, such as one or more HSP90 inhibitors.

  本发明提供了Ia、Ia′、IIa、IIa′、IIIa、IIIa′、IVa或Va配方的化合物及其治疗用途。本发明还包括使用紫霉素或其衍生物，例如公式I、II、III、IV、V、Ia、Ia′、IIa、IIa′、IIIa、IIIa′、IVa或Va中的一个或多个化合物，治疗NF2缺陷或NF1缺陷细胞或神经退行性疾病的方法。此外，本发明还涉及抑制NF2缺陷或NF1缺陷肿瘤生长的方法。该方法包括使用紫霉素或其衍生物，例如公式I、II、III、IV、V、Ia、Ia′、IIa、IIa′、IIIa、IIIa′、IVa或Va中的一个或多个化合物接触NF2缺陷或NF1缺陷肿瘤细胞。本发明还涉及紫霉素或其衍生物，例如公式I、II、III、IV、V、Ia、Ia′、IIa、IIa′、IIIa、IIIa′、IVa或Va与至少一种其他活性剂，例如一种或多种HSP90抑制剂的联合使用。