2-((4-hydroxy-2-iodo-5-methoxybenzyl)amino)-2-oxoethyl pentanoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-((4-hydroxy-2-iodo-5-methoxybenzyl)amino)-2-oxoethyl pentanoate
• 英文别名: [2-[(4-Hydroxy-2-iodo-5-methoxyphenyl)methylamino]-2-oxoethyl] pentanoate；[2-[(4-hydroxy-2-iodo-5-methoxyphenyl)methylamino]-2-oxoethyl] pentanoate
• 化学式: C₁₅H₂₀INO₅
• 分子量: 421.232
• InChiKey: QXSNCWIVCWUMKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  香兰素胺盐酸盐 在 咪唑 、 4-二甲氨基吡啶 、 四丁基氟化铵 、 碘 、 silver trifluoroacetate 、 sodium carbonate 、 溶剂黄146 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.5h， 生成 2-((4-hydroxy-2-iodo-5-methoxybenzyl)amino)-2-oxoethyl pentanoate
  参考文献：
  名称：

  轻柔地靶向瞬态受体潜在的香草酸1（TRPV1）通道：发现Passerini加合物可作为炎症性皮肤疾病的局部治疗方法

  摘要：

  尽管辣椒素是一种古老的分子，但它仍然是科学界的热门话题，开发新的辣椒素类药物是治疗与炎症和瘙痒有关的皮肤疾病的一种有前途的药理方法。在这里，我们报告了通过皮肤酯酶的水解活性而失活的辣椒素软药物的合成和评估。通过Passerini多组分反应将酯基植入辣椒素类化合物的亲脂部分中，可提供激动剂和拮抗剂，这些激动剂和拮抗剂保留了瞬时受体电位香草酸1通道（TRPV1）调节活性，并且同时易水解。鉴定出的最有希望的拮抗剂显示出对瘙痒和痛觉过敏的体内抗伤害感受活性，而不会产生体温过高，

  DOI：

  10.1021/acs.jmedchem.8b00109

文献信息

• TRPV1 MODULATOR COMPOUNDS
  申请人：Antalgenics, S.L.

  公开号：EP3401307A1

  公开（公告）日：2018-11-14

  The present invention relates to TRPV1 modulator compounds of formula (I) or their pharmaceutically or veterinary acceptable salts, or their stereoisomers or mixtures thereof, wherein m is an integer selected from 1 to 3; R1, R2, R6 and R6', are independently selected from H, (C1-C8)alkyl, unsaturated (C2-C8)hydrocarbon, and (C3-C6)cycloalkyl, being these groups optionally substituted; R3 is hydrogen or halogen; R4 is selected from H, (C1-C8)alkyl, unsaturated (C2-C8)hydrocarbon, (C3-C6)cycloalkyl, (C6-C12)aryl, and (C5-C12)heteroaryl, being these groups optionally substituted; and R5 is selected from (C3-C28)alkyl, unsaturated (C3-C28)hydrocarbon, (C6-C12)aryl, and (C5-C12)heteroaryl, being these groups optionally substituted. It also relates to a process for their preparation, to pharmaceutical, veterinary or cosmetic compositions containing them, and to their pharmaceutical, veterinary and cosmetic applications.

  本发明涉及公式（I）的TRPV1调节剂化合物或其药学或兽医可接受的盐，或其立体异构体或它们的混合物，其中m是从1到3选择的整数；R1、R2、R6和R6'分别从H、（C1-C8）烷基、不饱和（C2-C8）碳氢化合物和（C3-C6）环烷基中独立选择，这些基团可以选择性地被取代；R3是氢或卤素；R4从H、（C1-C8）烷基、不饱和（C2-C8）碳氢化合物、（C3-C6）环烷基、（C6-C12）芳基和（C5-C12）杂环芳基中选择，这些基团可以选择性地被取代；R5从（C3-C28）烷基、不饱和（C3-C28）碳氢化合物、（C6-C12）芳基和（C5-C12）杂环芳基中选择，这些基团可以选择性地被取代。它还涉及其制备方法，包含它们的药学、兽医或化妆品组合物，以及它们的药学、兽医和化妆品应用。
• TRPV1 Modulator Compounds
  申请人：ANTALGENICS, S.L.

  公开号：US20200199063A1

  公开（公告）日：2020-06-25

  The present invention relates to TRPV1 modulator compounds of formula (I) or their pharmaceutically, veterinary or cosmetically acceptable salts, or their stereoisomers or mixtures thereof, wherein m is an integer selected from 1 to 3; R 1 , R 2 , R 6 and R 6′ are independently selected from H, (C 1 -C 8 )alkyl, unsaturated (C 2 -C 8 )hydrocarbon, and (C 3 -C 6 )cycloalkyl, being these groups optionally substituted; R 3 is hydrogen or halogen; R 4 is selected from H, (C 1 -C 8 )alkyl, unsaturated (C 2 -C 8 )hydrocarbon, (C 3 -C 6 )cycloalkyl, (C 6 -C 12 )aryl, and (C 5 -C 12 )heteroaryl, being these groups optionally substituted; and R 5 is selected from (C 3 -C 28 )alkyl, unsaturated (C 3 -C 28 )hydrocarbon, (C 6 -C 12 )aryl, and (C 5 -C 12 )heteroaryl, being these groups optionally substituted. It also relates to a process for their preparation, to pharmaceutical, veterinary or cosmetic compositions containing them, and to their pharmaceutical, veterinary and cosmetic applications.
• [EN] TRPV1 MODULATOR COMPOUNDS<br/>[FR] COMPOSÉS MODULATEURS DE TRPV1
  申请人：ANTALGENICS S L

  公开号：WO2018206742A1

  公开（公告）日：2018-11-15

  The present invention relates to TRPV1 modulator compounds of formula (I) or their pharmaceutically, veterinary or cosmetically acceptable salts, or their stereoisomers or mixtures thereof, wherein m is an integer selected from 1 to 3; R1, R2, R6 and R6' are independently selected from H, (C1-C8)alkyl, unsaturated (C2-C8)hydrocarbon, and (C3-C6)cycloal kyI, being these groups optionally substituted; R3 is hydrogen or halogen; R4 is selected from H, (C1-C8)alkyl, unsaturated (C2-C8)hydrocarbon, (C3-C6)cycloalkyl, (C6-C12)aryl, and (C5-C12)heteroaryl, being these groups optionally substituted; and R5 is selected from (C3-C28)alkyl, unsaturated (C3-C28)hydrocarbon, (C6-C12)aryl, and (C5-C12) heteroaryI, being these groups optionally substituted. It also relates to a process for their preparation, to pharmaceutical, veterinary or cosmetic compositions containing them, and to their pharmaceutical, veterinary and cosmetic applications.
• Targeting Transient Receptor Potential Vanilloid 1 (TRPV1) Channel Softly: The Discovery of Passerini Adducts as a Topical Treatment for Inflammatory Skin Disorders
  作者：Marta Serafini、Alessia Griglio、Silvio Aprile、Fabio Seiti、Cristina Travelli、Franco Pattarino、Giorgio Grosa、Giovanni Sorba、Armando A. Genazzani、Sara Gonzalez-Rodriguez、Laura Butron、Isabel Devesa、Asia Fernandez-Carvajal、Tracey Pirali、Antonio Ferrer-Montiel

  DOI：10.1021/acs.jmedchem.8b00109

  日期：2018.5.24

  management of skin disorders related to inflammation and pruritus. Here we report the synthesis and the evaluation of capsaicin soft drugs that undergo deactivation by the hydrolyzing activity of skin esterases. The implanting of an ester group in the lipophilic moiety of capsaicinoids by the Passerini multicomponent reaction affords both agonists and antagonists that retain transient receptor potential vanilloid

  尽管辣椒素是一种古老的分子，但它仍然是科学界的热门话题，开发新的辣椒素类药物是治疗与炎症和瘙痒有关的皮肤疾病的一种有前途的药理方法。在这里，我们报告了通过皮肤酯酶的水解活性而失活的辣椒素软药物的合成和评估。通过Passerini多组分反应将酯基植入辣椒素类化合物的亲脂部分中，可提供激动剂和拮抗剂，这些激动剂和拮抗剂保留了瞬时受体电位香草酸1通道（TRPV1）调节活性，并且同时易水解。鉴定出的最有希望的拮抗剂显示出对瘙痒和痛觉过敏的体内抗伤害感受活性，而不会产生体温过高，