trisylhydrazone | 654674-38-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: trisylhydrazone
• 英文别名: 2,4,6-triisopropyl-N'-(1,4-dioxaspiro[4.5]decan-8-ylidene)benzenesulfonohydrazide；N-(1,4-dioxaspiro[4.5]decan-8-ylideneamino)-2,4,6-tri(propan-2-yl)benzenesulfonamide
• CAS: 654674-38-1
• 化学式: C₂₃H₃₆N₂O₄S
• 分子量: 436.616
• InChiKey: JFKBKNZBGFOOHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  85.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  trisylhydrazone 在 正丁基锂 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 正己烷 为溶剂， -78.0~23.0 ℃ 、101.33 kPa 条件下， 反应 7.58h， 生成 1,4-二噁螺[4.5]癸烷-8-甲醛
  参考文献：
  名称：

  [EN] FLUORO-PERHEXILINE COMPOUNDS AND THEIR THERAPEUTIC USE
  [FR] COMPOSÉS DE FLUORO-PERHEXILINE ET LEUR UTILISATION THÉRAPEUTIQUE

  摘要：

  本发明一般涉及治疗化合物领域。更具体地，本发明涉及以下式（在本文中也称为FPER化合物）的某些氟代perhexiline化合物，例如用于治疗包括已知可用perhexiline治疗或已知可用perhexiline治疗的紊乱（例如疾病），包括通过抑制肉碱棕榈酰基转移酶（CPT）改善的紊乱，如：心绞痛；心力衰竭（HF）；缺血性心脏病（IHD）；心肌病；心脏心律失常；心脏瓣膜狭窄；肥厚型心肌病（HCM）；冠心病；以及其他疾病，例如糖尿病和癌症。本发明还涉及包括这些化合物的药物组合物，以及这些化合物和组合物的用途，例如在治疗中的用途。

  公开号：

  WO2014184561A1
• 作为产物：
  描述：

  1,4-环己二酮单乙二醇缩酮 、 2,4,6-三异丙基苯磺酰基肼 在 盐酸 作用下， 以 甲醇 为溶剂， 以90%的产率得到trisylhydrazone
  参考文献：
  名称：

  （+/-）-加兰他敏的全合成。

  摘要：

  [反应：见正文]通过一种新颖的方法，从市售材料中获得了一种实用，有效的全合成（+/-）-加兰他敏，该方法的核心结构和特殊的烯丙醇基团的构建是基于连续的半松果酚的重排/去甲硅烷基化/环化和Saegusa-Ito氧化。

  DOI：

  10.1021/ol060339b

文献信息

• A general approach to crinine-type Amaryllidaceae alkaloids: total syntheses of (±)-haemanthidine, (±)-pretazettine, (±)-tazettine, and (±)-crinamine
  作者：Fu-Min Zhang、Yong-Qiang Tu、Jian-Dong Liu、Xiao-Hui Fan、Lei Shi、Xiang-Dong Hu、Shao-Hua Wang、Yong-Qiang Zhang

  DOI：10.1016/j.tet.2006.07.027

  日期：2006.10

  A general strategy for synthesizing the crinine-type Amaryllidaceae alkaloids was developed. And total syntheses of four representative crinine-type Amaryllidaceae alkaloids: (±)-haemanthidine, (±)-pretazettine, (±)-tazettine, and (±)-crinamine, were accomplished via a common intermediate 17. This crucial precursor was achieved on the basis of the NBS-promoted semipinacol rearrangement recently developed

  提出了合成可丽宁型金莲花科生物碱的一般策略。和的四个代表性crinine型全合成石蒜科生物碱：（±）-haemanthidine，（±）-pretazettine，（±）-tazettine，和（±）-crinamine，分别经由公共中间完成17。这个关键的前体是在我们的研究小组最近开发的NBS促进的半松果醇重排和分子内迈克尔加成的基础上实现的，后者分别有效地构建了可瑞宁型生物碱的空间拥挤的季碳中心和氢吲哚骨架。
• [EN] FLUORO-PERHEXILINE COMPOUNDS AND THEIR THERAPEUTIC USE<br/>[FR] COMPOSÉS DE FLUORO-PERHEXILINE ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：UNIV ABERDEEN

  公开号：WO2014184561A1

  公开（公告）日：2014-11-20

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain fluoro-perhexiline compounds of the following formula (also referred to herein as FPER compounds) that are useful, for example, in the treatment of disorders (e.g., diseases) including, for example, those which are known to be treated with, or known to be treatable with, perhexiline, including, for example, disorders that are ameliorated by the inhibition of carnitine palmitoyltransferase (CPT); cardiovascular disorders such as: angina pectoris; heart failure (HF); ischaemic heart disease (IHD); cardiomyopathy; cardiac dysrhythmia; stenosis of a heart valve; hypertrophic cardiomyopathy (HCM); coronary heart disease; and other disorders, for example, diabetes and cancer. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, for example, in therapy.

  本发明一般涉及治疗化合物领域。更具体地，本发明涉及以下式（在本文中也称为FPER化合物）的某些氟代perhexiline化合物，例如用于治疗包括已知可用perhexiline治疗或已知可用perhexiline治疗的紊乱（例如疾病），包括通过抑制肉碱棕榈酰基转移酶（CPT）改善的紊乱，如：心绞痛；心力衰竭（HF）；缺血性心脏病（IHD）；心肌病；心脏心律失常；心脏瓣膜狭窄；肥厚型心肌病（HCM）；冠心病；以及其他疾病，例如糖尿病和癌症。本发明还涉及包括这些化合物的药物组合物，以及这些化合物和组合物的用途，例如在治疗中的用途。
• Total Synthesis of (±)-Galanthamine
  作者：Xiang-Dong Hu、Yong Qiang Tu、En Zhang、Shuanhu Gao、Shaohua Wang、Aixia Wang、Chun-An Fan、Min Wang

  DOI：10.1021/ol060339b

  日期：2006.4.1

  [reaction: see text] A practical and efficient total synthesis of (+/-)-galanthamine was achieved from commercially available materials through a novel approach, in which the construction of its core structure and the special allylic alcohol group were based on a successive semipinacol rearrangement/desilyation/cyclization and Saegusa-Ito oxidation, respectively.

  [反应：见正文]通过一种新颖的方法，从市售材料中获得了一种实用，有效的全合成（+/-）-加兰他敏，该方法的核心结构和特殊的烯丙醇基团的构建是基于连续的半松果酚的重排/去甲硅烷基化/环化和Saegusa-Ito氧化。
• FLUORO-PERHEXILINE COMPOUNDS AND THEIR THERAPEUTIC USE
  申请人：THE UNIVERSITY COURT OF THE UNIVERSITY OF ABERDEEN

  公开号：US20160102058A1

  公开（公告）日：2016-04-14

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain fluoro-perhexiline compounds of the following formula (also referred to herein as FPER compounds) that are useful, for example, in the treatment of disorders (e.g., diseases) including, for example, those which are known to be treated with, or known to be treatable with, perhexiline, including, for example, disorders that are ameliorated by the inhibition of carnitine palmitoyltransferase (CPT); cardiovascular disorders such as: angina pectoris; heart failure (HF); ischaemic heart disease (IHD); cardiomyopathy; cardiac dysrhythmia; stenosis of a heart valve; hypertrophic cardiomyopathy (HCM); coronary heart disease; and other disorders, for example, diabetes and cancer. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, for example, in therapy.

  本发明一般涉及治疗化合物领域。更具体地，本发明涉及下列公式的某些氟代perhexiline化合物（在此称为FPER化合物），例如用于治疗障碍（例如疾病），包括那些已知可以用perhexiline治疗或可以用perhexiline治疗的障碍，包括例如通过抑制肉碱棕榈酰转移酶（CPT）改善的障碍：心绞痛，心力衰竭（HF），缺血性心脏病（IHD），心肌病，心脏心律失常，心脏瓣膜狭窄，肥厚型心肌病（HCM），冠心病以及其他障碍，例如糖尿病和癌症。本发明还涉及包含这些化合物的制药组合物，以及这些化合物和组合物的使用，例如在治疗中的使用。
• Development of Fluorinated Analogues of Perhexiline with Improved Pharmacokinetic Properties and Retained Efficacy
  作者：Chih-Chung Tseng、Hannah Noordali、Monica Sani、Melanie Madhani、Denis M. Grant、Michael P. Frenneaux、Matteo Zanda、Iain R. Greig

  DOI：10.1021/acs.jmedchem.6b01592

  日期：2017.4.13

  We designed and synthesized perhexiline analogues that have the same therapeutic profile as the parent cardiovascular drug but lacking its metabolic liability associated with CYP2D6 metabolism. Cycloalkyl perhexiline analogues 6a-j were found to be unsuitable for further development, as they retained a pharmacokinetic profile very similar to that shown by the parent compound. Multistep synthesis of perhexiline analogues incorporating fluorine atoms onto the cyclohexyl ring(s) provided a range of different fluoroperhexiline analogues. Of these, analogues 50 (4,4-gem-difluoro) and 62 (4,4,4',4'-tetrafluoro) were highly stable and showed greatly reduced susceptibility to CYP2D6-mediated metabolism. In vitro efficacy studies demonstrated that a number of derivatives retained acceptable potency against CPT-1. Having the best balance of properties, 50 was selected for further evaluation. Like perhexiline, it was shown to be selectively concentrated in the myocardium and, using the Langendorff model, to be effective in improving both cardiac contractility and relaxation when challenged with high fat buffer.