(R)-3-decyloxytetradecanoic acid | 1092962-70-3

• 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: (R)-3-decyloxytetradecanoic acid
• 英文别名: (3R)-3-decoxytetradecanoic acid
• CAS: 1092962-70-3
• 化学式: C₂₄H₄₈O₃
• 分子量: 384.643
• InChiKey: ROYVLWKXIKKQQP-HSZRJFAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.7
• 重原子数：
  27
• 可旋转键数：
  22
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-3-decyloxytetradecanoic acid 在 三氟化硼乙醚 、 1-[3-(dimethylamino)-propyl]-3-ethylcarbodiimide methiodide 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Characterization of TRIF selectivity in the AGP class of lipid A mimetics: Role of secondary lipid chains

  摘要：

  TLR4 agonists that favor TRIF-dependent signaling and the induction of type 1 interferons may have potential as vaccine adjuvants with reduced toxicity. CRX-547 (4), a member of the aminoalkyl glucosaminide 4-phosphate (AGP) class of lipid A mimetics possessing three (R)-3-decanoyloxytetradecanoyl groups and D-relative configuration in the aglycon, selectively reduces MyD88-dependent signaling resulting in TRIF-selective signaling, whereas the corresponding secondary ether lipid 6a containing (R)-3-decyloxytetradecanoyl groups does not. In order to determine which secondary acyl groups are important for the reduction in MyD88-dependent signaling activity of 4, the six possible ester/ether hybrid derivatives of 4 and 6a were synthesized and evaluated for their ability to induce NF-kappa B in a HEK293 cell reporter assay. An (R)-3-decanoyloxytetradecanoyl group on the 3-position of the D-glucosamine unit was found to be indispensable for maintaining low NF-kappa B activity irrespective of the substitutions (decyl or decanoyl) on the other two secondary positions. These results suggest that the carbonyl group of the 3-secondary lipid chain may impede homodimerization and/or conformational changes in the TLR4-MD2 complex necessary for MyD88 binding and pro-inflammatory cytokine induction. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.024
• 作为产物：
  描述：

  2-(4-bromophenyl)-2-oxoethyl (R)-3-(decyloxy)tetradecanoate 在 lithium hydroxide 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以90%的产率得到(R)-3-decyloxytetradecanoic acid
  参考文献：
  名称：

  The ‘Ethereal’ nature of TLR4 agonism and antagonism in the AGP class of lipid A mimetics

  摘要：

  To overcome the chemical and metabolic instability of the secondary fatty acyl residues in the AGP class of lipid A mimetics, the secondary ether lipid analogs of the potent TLR4 agonist CRX-527 (2) and TLR4 antagonist CRX-526 (3) were synthesized and evaluated along with their ester counterparts for agonist/antagonist activity in both in vitro and in vivo models. Like CRX-527, the secondary ether lipid 4 showed potent agonist activity in both murine and human models. Ether lipid 5, on the other hand, showed potent TLR4 antagonist activity similar to CRX-526 in human cell assays, but did not display any antagonist activity in murine models and, in fact, was weakly agonistic. Glycolipids 2, 4, and 5 were synthesized via a new highly convergent method utilizing a common advanced intermediate strategy. A new method for preparing (R)-3-alkyloxytetradecanoic acids, a key component of ether lipids 4 and 5, is also described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.09.060

文献信息

• [EN] TLR4 COMPOUNDS OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, CORRESPONDING PHARMACEUTICAL COMPOSITIONS OR FORMULATIONS, METHODS OF PREPARATION, TREATMENT OR USES<br/>[FR] COMPOSÉS TLR4 OU SELS PHARMACEUTIQUEMENT ACCEPTABLES DE CEUX-CI, COMPOSITIONS OU FORMULATIONS PHARMACEUTIQUES CORRESPONDANTES, PROCÉDÉS DE PRÉPARATION, TRAITEMENT OU UTILISATIONS
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2020007760A1

  公开（公告）日：2020-01-09

  The present invention relates to novel pharmaceutically acceptable salts of TLR4 agonist compounds and forms thereof, corresponding pharmaceutical compositions or formulations, processes or methods of compound preparation and uses or treatment methods for cancers, which includes associated cancer immunotherapies (i.e., also known as immuno-oncology).

  本发明涉及一种新型药物可接受的TLR4激动剂化合物及其形式的盐，相应的药物组成物或配方，化合物制备的过程或方法以及用于癌症的治疗方法或方法，包括相关的癌症免疫治疗（即也称为免疫肿瘤学）。
• Diamino Allose Phosphates: Novel, Potent, and Highly Stable Toll-like Receptor 4 Agonists
  作者：Juhienah K. Khalaf、Laura S. Bess、Lois M. Walsh、Janine M. Ward、Craig L. Johnson、Mark T. Livesay、Konner J. Jackson、Jay T. Evans、Kendal T. Ryter、Hélène G. Bazin-Lee

  DOI：10.1021/acs.jmedchem.3c00724

  日期：2023.10.26

  synthetic toll-like receptor 4 (TLR4) agonists are carbohydrate-based lipid-A mimetics containing several fatty acyl chains, including a labile 3-O-acyl chain linked to the C-3 position of the non-reducing sugar known to undergo cleavage impacting stability and resulting in loss of activity. To overcome this inherent instability, we rationally designed a new class of chemically more stable synthetic TLR4

  最已知的合成 Toll 样受体 4 (TLR4) 激动剂是基于碳水化合物的脂质 A 模拟物，含有多个脂肪酰基链，包括与已知的非还原糖的 C-3 位连接的不稳定 3- O-酰基链。发生裂解，影响稳定性并导致活性丧失。为了克服这种固有的不稳定性，我们合理地设计了一类化学上更稳定的合成 TLR4 配体，可引发强大的先天性和适应性免疫反应。该新类别使用含有不可水解的 3-酰胺键的二氨基阿洛糖磷酸 (DAP) 支架，而不是经典的 3-酯。因此，相对于其他已知的天然和合成TLR4配体，DAP在水性制剂中的热稳定性和效力显着改善。此外，DAP 类似物可作为有效的疫苗佐剂，增强小鼠体内的流感特异性抗体，并提供针对致命流感病毒挑战的保护。这组新颖的 TLR4 配体有望成为下一代疫苗佐剂和独立的免疫调节剂。
• Certain aminoalkyl glucosaminide phosphate compounds and their use
  申请人：Johnson A. David

  公开号：US20050227943A1

  公开（公告）日：2005-10-13

  Compounds that are adjuvants and immunoeffectors are described and claimed. The compounds augment antibody production in immunized animals as well as stimulate cytokine production and activate macrophages. Compositions and methods for using the compounds as adjuvants and immunoeffectors are also disclosed.

  本文描述并声称了作为佐剂和免疫效应剂的化合物。 这些化合物能增强免疫动物体内抗体的产生，刺激细胞因子的产生并激活巨噬细胞。 还公开了将这些化合物用作佐剂和免疫效应剂的组合物和方法。
• CERTAIN AMINOALKYL GLUCOSAMINIDE PHOSPHATE COMPOUNDS AND THEIR USE
  申请人：CORIXA CORPORATION

  公开号：EP1589934A2

  公开（公告）日：2005-11-02
• EP1776375B1
  申请人：——

  公开号：EP1776375B1

  公开（公告）日：2015-04-01