(4Z)-5,9-dimethyl-4,8-decadienoic acid | 41515-53-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (4Z)-5,9-dimethyl-4,8-decadienoic acid
• 英文别名: bishomonerolic acid；Geranylessigsaeure；cis-Geranylessigsaeure；Nerylacetic acid；(4Z)-5,9-dimethyldeca-4,8-dienoic acid
• CAS: 41515-53-1
• 化学式: C₁₂H₂₀O₂
• 分子量: 196.29
• InChiKey: HPOYZGTYWKRTPU-FLIBITNWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4Z)-5,9-dimethyl-4,8-decadienoic acid 在 lithium aluminium tetrahydride 、 sodium azide 、 copper(II) sulfate 、 sodium ascorbate 、 三乙胺 、 lithium bromide 作用下， 以 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 叔丁醇 为溶剂， 反应 50.5h， 生成 tetraethyl (4Z)-(2-(1-(5,9-dimethyldeca-4,8-dienyl)-1H-1,2,3-triazol-4-yl)ethane-1,1-diyl)bis(phosphonate)
  参考文献：
  名称：

  Bishomoisoprenoid triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase

  摘要：

  Protein geranylgeranylation reactions are dependent on the availability of geranylgeranyl diphosphate (GGDP), which serves as the isoprenoid donor. Inhibition of GGDP synthase (GGDPS) is of interest from a drug development perspective as GGDPS inhibition results in impaired protein geranylgeranylation, which in multiple myeloma, disrupts monoclonal protein trafficking and induces apoptosis. We have recently reported a series of isoprenoid triazole bisphosphonates and have demonstrated that a 3:1 mixture of homogeranyl and homoneryl isomers potently, and in a synergistic manner, inhibits GGDPS. We now present the synthesis and biological evaluation of a novel series of bishomoisoprenoid triazoles which furthers our understanding of the structure-function relationship of this class. These studies demonstrate the importance of chain length and olefin stereochemistry on inhibitory activity. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.02.066
• 作为产物：
  描述：

  (Z)-neryl bromide 在 吡啶 、 sodium hydride 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 mineral oil 为溶剂， 反应 2.5h， 生成 (4Z)-5,9-dimethyl-4,8-decadienoic acid
  参考文献：
  名称：

  Bishomoisoprenoid triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase

  摘要：

  Protein geranylgeranylation reactions are dependent on the availability of geranylgeranyl diphosphate (GGDP), which serves as the isoprenoid donor. Inhibition of GGDP synthase (GGDPS) is of interest from a drug development perspective as GGDPS inhibition results in impaired protein geranylgeranylation, which in multiple myeloma, disrupts monoclonal protein trafficking and induces apoptosis. We have recently reported a series of isoprenoid triazole bisphosphonates and have demonstrated that a 3:1 mixture of homogeranyl and homoneryl isomers potently, and in a synergistic manner, inhibits GGDPS. We now present the synthesis and biological evaluation of a novel series of bishomoisoprenoid triazoles which furthers our understanding of the structure-function relationship of this class. These studies demonstrate the importance of chain length and olefin stereochemistry on inhibitory activity. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.02.066

文献信息

• Amides as bioisosteres of triazole-based geranylgeranyl diphosphate synthase inhibitors
  作者：Daniel B. Goetz、Michelle L. Varney、David F. Wiemer、Sarah A. Holstein

  DOI：10.1016/j.bmc.2020.115604

  日期：2020.8

  synthase (GGDPS) inhibitors are of potential therapeutic interest as a consequence of their activity against the bone marrow cancer multiple myeloma. A series of bisphosphonates linked to an isoprenoid tail through an amide linkage has been prepared and tested for the ability to inhibit GGDPS in enzyme and cell-based assays. The amides were designed as analogues to triazole-based GGDPS inhibitors. Several

  香叶基香叶基二磷酸合酶 (GGDPS) 抑制剂因其对骨髓癌多发性骨髓瘤的活性而具有潜在的治疗意义。已经制备了一系列通过酰胺键连接到类异戊二烯尾部的双膦酸盐，并在基于酶和细胞的测定中测试了抑制 GGDPS 的能力。酰胺被设计为类似于基于三唑的 GGDPS 抑制剂。几种新化合物在酶和细胞测定中均显示出 GGDPS 抑制活性，其效力取决于链长和烯烃立体化学。
• Bisphosphonate squalene synthetase inhibitors
  申请人：E.R. SQUIBB & SONS, INC.

  公开号：EP0513761A2

  公开（公告）日：1992-11-19

  Compounds which are inhibitors of cholesterol biosynthesis (by inhibiting de novo squalene biosynthesis), and thus are useful as hypocholesterolemic agents and antiatherosclerotic agents are provided which have the structure and analogs thereof, wherein R¹, R², R³ and R⁴ are the same or different and are H, lower alkyl, a metal ion or a prodrug ester;    R⁵ is H, halogen or lower alkyl;    Zq is substituted alkenyl, substituted alkynyl, mixed alkenyl-alkynyl or substituted phenylalkyl, or substituted biphenylalkyl, alkylphenylalkyl or alkyl, including all stereoisomers thereof. New methods for using such compounds to inhibit cholesterol biosynthesis are also provided.

  所提供的化合物是胆固醇生物合成的抑制剂（通过抑制角鲨烯的新生物合成），因此可用作降胆固醇药和抗动脉粥样硬化药，其结构为 及其类似物，其中 R¹、R²、R³ 和 R⁴ 相同或不同，并且是 H、低级烷基、金属离子或原药酯； R⁵ 是 H、卤素或低级烷基； Zq 是取代的烯基、取代的炔基、混合烯基-炔基或取代的苯基烷基，或取代的联苯烷基、 烷基苯烷基或烷基，包括其所有立体异构体。 还提供了使用此类化合物抑制胆固醇生物合成的新方法。
• Use of phosphonomethylphosphinate squalene synthetase inhibitors for the manufacture of a medicament for the lowering cholesterol
  申请人：E.R. SQUIBB & SONS, INC.

  公开号：EP0514124A2

  公开（公告）日：1992-11-19

  A method is provided for inhibiting cholesterol biosynthesis by inhibiting de novo squalene production employing methylene phosphonoalkylphosphinate compounds.

  提供了一种利用亚甲基膦酰基膦化合物抑制角鲨烯从头生成，从而抑制胆固醇生物合成的方法。
• Perfume particles and a process for preparing the same
  申请人：KAO CORPORATION

  公开号：EP1600151A1

  公开（公告）日：2005-11-30

  Perfume particles suitable to be used in detergents and cleansing agents and a method for preparing the same are described in the present invention. The perfume particles comprise a perfume, a water-soluble or in water dispersible carrier material and water-insoluble silica as powdering agent. The perfume particles of the present invention are flowable, resistant to storage and show good fragrance characteristics.

  本发明描述了适用于洗涤剂和清洁剂的香水微粒及其制备方法。香水微粒由香水、水溶性或在水中可分散的载体材料和作为粉末剂的不溶于水的二氧化硅组成。本发明的香水微粒具有流动性、耐储存性和良好的香味特性。
• Verfahren zur Herstellung von 1-funktionellen Allyalkohol-Carbonsäureestern
  申请人：Dragoco Gerberding & Co Aktiengesellschaft

  公开号：EP0861822B1

  公开（公告）日：2001-07-04