MEM-homovanillic acid | 179258-48-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: MEM-homovanillic acid
• 英文别名: 2-[3-Methoxy-4-(2-methoxyethoxymethoxy)phenyl]acetic acid
• CAS: 179258-48-1
• 化学式: C₁₃H₁₈O₆
• 分子量: 270.282
• InChiKey: JYDULNXLSBPAAC-UHFFFAOYSA-N

物化性质

• 沸点：
  414.9±45.0 °C(Predicted)
• 密度：
  1.190±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  MEM-homovanillic acid 在 4-二甲氨基吡啶 、 四氯化锡 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 佛波醇 12-苯乙酸酯 13-乙酸酯 20-高香草酸酯
  参考文献：
  名称：

  Synthesis and Evaluation of Phorboid 20-Homovanillates:  Discovery of a Class of Ligands Binding to the Vanilloid (Capsaicin) Receptor with Different Degrees of Cooperativity

  摘要：

  A number of phorboid 20-homovanillates were prepared by condensation of phorbol 12,13-diesters and 12-dehydrophorbol 13-esters with Mem-homovanillic acid followed by removal of the protecting group with SnCl4 in THF. These compounds were evaluated for their ability to inhibit [H-3]resiniferatoxin (RTX) binding to rat spinal cord membranes. Compounds bearing a lipophilic ester group on ring C were considerably active, but a surprising tolerance of the vanilloid receptor toward the location and the orientation of this ester group was disclosed. Unexpectedly, these ligands could also diminish, to a variable degree, the positive cooperativity which characterizes RTX binding to the vanilloid receptor. Phorbol 12-phenylacetate 13-acetate 20-homovanillate (PPAHV, 6a), a compound which abolished binding cooperativity, was further tested in a variety of in vivo assays used to characterize vanilloid-like activity. PPAHV showed only a marginal pungency and failed to induce a measurable hypothermia response at doses (up to 200 mg/kg) at which it effectively desensitized against neurogenic inflammation. These data suggest that the peculiar binding behavior of these ligands might be associated with a distinct spectrum of biological activity.

  DOI：

  10.1021/jm960063l
• 作为产物：
  描述：

  4-羟基-3-甲氧基苯乙腈 在 氢氧化钾 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 60.0h， 生成 MEM-homovanillic acid
  参考文献：
  名称：

  Synthesis and Evaluation of Phorboid 20-Homovanillates:  Discovery of a Class of Ligands Binding to the Vanilloid (Capsaicin) Receptor with Different Degrees of Cooperativity

  摘要：

  A number of phorboid 20-homovanillates were prepared by condensation of phorbol 12,13-diesters and 12-dehydrophorbol 13-esters with Mem-homovanillic acid followed by removal of the protecting group with SnCl4 in THF. These compounds were evaluated for their ability to inhibit [H-3]resiniferatoxin (RTX) binding to rat spinal cord membranes. Compounds bearing a lipophilic ester group on ring C were considerably active, but a surprising tolerance of the vanilloid receptor toward the location and the orientation of this ester group was disclosed. Unexpectedly, these ligands could also diminish, to a variable degree, the positive cooperativity which characterizes RTX binding to the vanilloid receptor. Phorbol 12-phenylacetate 13-acetate 20-homovanillate (PPAHV, 6a), a compound which abolished binding cooperativity, was further tested in a variety of in vivo assays used to characterize vanilloid-like activity. PPAHV showed only a marginal pungency and failed to induce a measurable hypothermia response at doses (up to 200 mg/kg) at which it effectively desensitized against neurogenic inflammation. These data suggest that the peculiar binding behavior of these ligands might be associated with a distinct spectrum of biological activity.

  DOI：

  10.1021/jm960063l

文献信息

• A novel agonist, phorbol 12-phenylacetate 13-acetate 20-homovanillate, abolishes positive cooperativity of binding by the vanilloid receptor
  作者：Arpad Szallasi、Geza Acs、Giancarlo Cravotto、Peter M. Blumberg、Jan M. Lundberg、Giovanni Appendino

  DOI：10.1016/0014-2999(95)00864-0

  日期：1996.3

  capsazepine. Upon binding to its receptor, capsaicin opens a cation channel leading to Ca2+ influx. The binding of capsaicin or resiniferatoxin by the vanilloid receptor follows a sigmoidal saturation curve, indicative of positive cooperativity. The biological significance of this positive cooperative behaviour is unknown, as is the mechanism responsible for it. We have developed a novel ligand, phorbol

  辣椒素与特定的识别位点结合，称为香草素受体，与天然的超强效激动剂resiniferatoxin和竞争性拮抗剂辣椒素共有。辣椒素与其受体结合后，打开一个阳离子通道，导致Ca2 +大量涌入。辣椒素受体与辣椒素或树脂毒素的结合遵循S形饱和曲线，表明正协同性。这种积极的合作行为的生物学意义以及导致这种行为的机制尚不清楚。我们已经开发出一种新型配体，佛波醇12-苯基乙酸13-乙酸20-异戊酸酯（PPAHV），它与培养的大鼠感觉神经元（Ki为3.1 +/- 0.4 microM）结合，并诱导它们吸收Ca2 +（ ED50为1.8 +/- 0。3 microM）具有相似的亲和力并且以非合作方式进行（结合和Ca2 +吸收的希尔系数分别为0.99和1.06）。PPAHV的行为因此与树脂毒素或辣椒素形成对比，不仅缺乏协同性，而且树脂脂毒素结合与Ca2 +吸收的相对效力也有所不同（树脂毒素毒素的效力较弱，而辣椒素对Ca2
• NOUVEAUX DÉRIVÉS D'ACIDE 3-PHENYL ACRYLIQUE ACTIVATEURS DES RÉCEPTEURS DE TYPE PPAR, LEUR MÉTHODE DE PRÉPARATION ET LEUR UTILISATION DANS DES COMPOSITIONS COSMÉTIQUES OU PHARMACEUTIQUES
  申请人：Galderma Research & Development

  公开号：EP2164827A2

  公开（公告）日：2010-03-24
• [EN] NOVEL DERIVATIVES OF 3-PHENYL ACRYLIC ACID ACTIVATING PPAR-TYPE RECEPTORS, METHOD FOR PREPARING SAME AND USE THEREOF IN COSMETIC OR PHARMACEUTICAL COMPOSITIONS<br/>[FR] NOUVEAUX DÉRIVÉS D'ACIDE 3-PHENYL ACRYLIQUE ACTIVATEURS DES RÉCEPTEURS DE TYPE PPAR, LEUR MÉTHODE DE PRÉPARATION ET LEUR UTILISATION DANS DES COMPOSITIONS COSMÉTIQUES OU PHARMACEUTIQUES
  申请人：GALDERMA RES & DEV

  公开号：WO2008152334A2

  公开（公告）日：2008-12-18

  [EN] The invention relates to novel derivatives of 3-phenyl acrylic acid of the following general formula (I), to a method for preparing the same, and to the use thereof in pharmaceutical compositions used in human or veterinary medicine (in dermatology as well as in the field of cardio-vascular diseases, immune diseases and/or diseases related to lipid metabolism), or in cosmetic compositions.
  [FR] L'invention concerne de nouveaux dérivés d'acide 3-phenyl acrylique qui répondent à la formule générale (I) suivante: ainsi que leur méthode de préparation, et leur utilisation dans des compositions pharmaceutiques destinées à un usage en médecine humaine ou vétérinaire (en dermatologie, ainsi que dans le domaine des maladies cardio-vasculaires, des maladies immunitaires et/ou des maladies liées au métabolisme des lipides), ou bien encore dans des compositions cosmétiques.
• Synthesis and Evaluation of Phorboid 20-Homovanillates:  Discovery of a Class of Ligands Binding to the Vanilloid (Capsaicin) Receptor with Different Degrees of Cooperativity
  作者：Giovanni Appendino、Giancarlo Cravotto、Giovanni Palmisano、Rita Annunziata、Arpad Szallasi

  DOI：10.1021/jm960063l

  日期：1996.1.1

  A number of phorboid 20-homovanillates were prepared by condensation of phorbol 12,13-diesters and 12-dehydrophorbol 13-esters with Mem-homovanillic acid followed by removal of the protecting group with SnCl4 in THF. These compounds were evaluated for their ability to inhibit [H-3]resiniferatoxin (RTX) binding to rat spinal cord membranes. Compounds bearing a lipophilic ester group on ring C were considerably active, but a surprising tolerance of the vanilloid receptor toward the location and the orientation of this ester group was disclosed. Unexpectedly, these ligands could also diminish, to a variable degree, the positive cooperativity which characterizes RTX binding to the vanilloid receptor. Phorbol 12-phenylacetate 13-acetate 20-homovanillate (PPAHV, 6a), a compound which abolished binding cooperativity, was further tested in a variety of in vivo assays used to characterize vanilloid-like activity. PPAHV showed only a marginal pungency and failed to induce a measurable hypothermia response at doses (up to 200 mg/kg) at which it effectively desensitized against neurogenic inflammation. These data suggest that the peculiar binding behavior of these ligands might be associated with a distinct spectrum of biological activity.