3,3-Dimethyl-5-hexynoic acid | 92898-15-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 3,3-Dimethyl-5-hexynoic acid
• 英文别名: 3,3-Dimethylhex-5-ynoic acid
• CAS: 92898-15-2
• 化学式: C₈H₁₂O₂
• 分子量: 140.182
• InChiKey: QNIOGKVSLMRMAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.62
• 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：

  3,3-Dimethyl-5-hexynoic acid 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 二乙胺 、 乙酰氯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 Methyl 6-(2-aminophenyl)-3,3-dimethylhex-5-ynoate
  参考文献：
  名称：

  [EN] HSP-90 BINDING COMPOUNDS, COMPOSITIONS THEREOF, AND THEIR USE FN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISEASES
  [FR] COMPOSÉS SE FIXANT À LA HSP-90, COMPOSITIONS DE CEUX-CI ET LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES AUTO-IMMUNES ET INFLAMMATOIRES

  摘要：

  这项发明涉及与HSP90结合的治疗化合物。本文所披露的化合物与HSP90结合并改变HSP90蛋白的分子伴侣能力。该发明还涉及包含这些化合物的药物组合物，以及治疗癌症、自身免疫疾病和其他疾病的方法。

  公开号：

  WO2011035417A1
• 作为产物：
  描述：

  2,2-二甲基-4-戊炔-1-醇甲苯磺酸酯 在 氢氧化钾 作用下， 以 二甲基亚砜 为溶剂， 反应 6.0h， 生成 3,3-Dimethyl-5-hexynoic acid
  参考文献：
  名称：

  New approaches to the synthesis of alkyl-substituted enol lactone systems, inhibitors of the serine protease elastase

  摘要：

  We have synthesized a series of alkyl-substituted enol lactones designed to act as mechanism-based inhibitors of human neutrophil elastase (HLE). General methods were developed for the preparation of alpha- and beta-alkyl-substituted 5-hexynoic acids by the bromoform reaction on the corresponding alkynoic methyl ketone, prepared by an Eschenmoser-Tanabe fragmentation sequence from a suitably substituted cyclohexenone. By this method, beta-methyl- and beta,beta-dimethyl-5-hexynoic acids were synthesized from commercially available isophorone and 3,5-dimethyl-2-cyclohexen-1-one, respectively. Alpha-Substituted 5-hexynoic acids were prepared from 3-ethoxy-2-cyclohexen-1-one, using a novel ZnCl2-mediated alkylation that we developed; this method gives high yields of alpha'-alkylation products, even with secondary halides. The most efficient method for the preparation of alpha-substituted 5-hexynoic acids involved a four-reaction sequence-alkylation of the alpha-substituted ester with 1,4-dibromobutane, elimination, bromination and bisdehydrobromination-that proceeded in high overall yield. Protio enol lactonizations were performed with mercury(II) catalysis in CH2Cl2 or CH2Cl2-H2O. Stereo-selective Z-bromo enol lactonization was carried out by Br+-induced lactonization in the presence of Ag+. E-Bromo enol lactonization with N-bromosuccinimide in CH2Cl2 in the presence of a small amount of water gave better yields and shorter reaction times than the traditional anhydrous conditions. In studies of the inhibitory activity of these lactones toward several proteases (reported in full elsewhere), we found that the alpha-alkyl-substituted protio and bromo enol lactones 1-3 were very good inhibitors of HLE, with k(a)/K(i) values ranging from 14 500 to 37 500 M-1 s-1; the beta-alkyl-substituted enol lactones 5-8 showed only moderate inhibition of HLE.

  DOI：

  10.1021/jo00059a049

文献信息

• [EN] HSP-90 BINDING COMPOUNDS, COMPOSITIONS THEREOF, AND THEIR USE I? THE TREATMENT AND PREVENTION OF FUNGAL INFECTIONS<br/>[FR] COMPOSÉS DE LIAISON À HSP-90, COMPOSITIONS DE CES COMPOSÉS, ET UTILISATIONS DE CES COMPOSÉS POUR LE TRAITEMENT ET LA PRÉVENTION D'INFECTIONS FONGIQUES
  申请人：PHARMASCIENCE INC

  公开号：WO2012126084A1

  公开（公告）日：2012-09-27

  The invention relates to therapeutic compounds that bind to HSP90. The compounds disclosed herein bind HSP90 and alter the chaperoning capability of HSP90 proteins. The invention also relates to pharmaceutical compositions comprising these compounds, and methods of treating or preventing fungal infections.

  该发明涉及与HSP90结合的治疗化合物。本文披露的化合物与HSP90结合并改变HSP90蛋白的分子伴侣能力。该发明还涉及包含这些化合物的药物组合物，以及治疗或预防真菌感染的方法。
• Obtention de δ-methylene δ-lactones et de δ-lactones γ-ethyleniques
  作者：Abdelkébir Jellal、Jacques Grimaldi、Maurice Santelli

  DOI：10.1016/s0040-4039(01)91002-0

  日期：1984.1
• Stereoselective Z- and E-bromoenol lactonization of alkynoic acids
  作者：Wei Dai、John A. Katzenellenbogen

  DOI：10.1021/jo00024a035

  日期：1991.11

  We have found that treatment of the silver salt of a 4- or 5-terminal alkynoic acid with bromine results in clean formation of the corresponding Z-bromo enol lactone, the result of a formal cis addition of carboxylate and bromine across the triple bond. This Z-bromo enol lactonization is highly stereoselective and gives good yields in systems that bear substituents on the internal methylene groups; yields with unsubstituted or terminally substituted alkynoic acids are modest. The E-bromo enol lactonization reaction, reported by us previously (Krafft, G. A.; Katzenellenbogen, J. A. J. Am. Chem. Soc. 1981, 103, 5459), has a broader scope and, with modifications, can be performed with high reliability. Mercury(II) salts equilibrate the Z- and E-bromo enol lactones, presumedly by a mercuric ion addition-elimination mechanism. These three reactions provide access to an array of stereoisomeric bromo enol lactone systems.
• JELLAL, A.;GRIMALDI, J.;SANTELLI, M., TETRAHEDRON LETT., 1984, 25, N 30, 3179-3182
  作者：JELLAL, A.、GRIMALDI, J.、SANTELLI, M.

  DOI：——

  日期：——
• [EN] HSP-90 BINDING COMPOUNDS, COMPOSITIONS THEREOF, AND THEIR USE FN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISEASES<br/>[FR] COMPOSÉS SE FIXANT À LA HSP-90, COMPOSITIONS DE CEUX-CI ET LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES AUTO-IMMUNES ET INFLAMMATOIRES
  申请人：AEGERA THERAPEUTICS INC

  公开号：WO2011035417A1

  公开（公告）日：2011-03-31

  The invention relates to therapeutic compounds that bind to HSP90. The compounds disclosed herein bind HSP90 and alter the chaperoning capability of HSP90 proteins. The invention also relates to pharmaceutical compositions comprising these compounds, and methods of treating diseases and disorders such as cancer, autoimmune disease and other diseases.

  这项发明涉及与HSP90结合的治疗化合物。本文所披露的化合物与HSP90结合并改变HSP90蛋白的分子伴侣能力。该发明还涉及包含这些化合物的药物组合物，以及治疗癌症、自身免疫疾病和其他疾病的方法。