CRX-527

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: CRX-527
• 英文别名: N-[(3R)-3-(Decanoyloxy)myristoyl]-O-[2-[[(3R)-3-(decanoyloxy)myristoyl]amino]-3-O-[(3R)-3-(decanoyloxy)myristoyl]-4-O-phosphono-2-deoxy-beta-D-glucopyranosyl]-L-serine；(2S)-2-[[(3R)-3-decanoyloxytetradecanoyl]amino]-3-[(2R,3R,4R,5S,6R)-3-[[(3R)-3-decanoyloxytetradecanoyl]amino]-4-[(3R)-3-decanoyloxytetradecanoyl]oxy-6-(hydroxymethyl)-5-phosphonooxyoxan-2-yl]oxypropanoic acid
• 化学式: C₈₁H₁₅₁N₂O₁₉P
• 分子量: 1488.07
• InChiKey: REEGNIYAMZUTIO-MGSMBCBTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  24.5
• 重原子数：
  103
• 可旋转键数：
  77
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  306
• 氢给体数：
  6
• 氢受体数：
  19

反应信息

• 作为产物：
  描述：

  benzyl (2S)-3-[(4-O-[bis(benzyloxy)phosphoryl]-3-O-[(3R)-3-(decanoyloxy)tetradecanoyl]-2-{ [(3R)-3-(decanoyloxy)tetradecanoyl]amino}-2-deoxy-β-D-glucopyranosyl)oxy]-2-{ [(3R)-3-(decanoyloxy)tetradecanoyl]amino}propanoate 在 palladium hydroxide on carbon 、 氢气 作用下， 以 四氢呋喃 为溶剂， 以65%的产率得到CRX-527
  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

• Aminoalkyl glucosaminide phosphate compounds and their use as adjuvants and immunoeffectors
  申请人：Corixa Corporation

  公开号：US20030092643A1

  公开（公告）日：2003-05-15

  Aminoalkyl glucosaminide phosphate (AGP) compounds that are adjuvants and immunoeffectors are described and claimed. The compounds have a 2-deoxy-2-amino glucose in glycosidic linkage with an aminoalkyl (aglycon) group. Compounds are phosphorylated at the 4 or 6 carbon on the glucosaminide ring and comprise three 3- alkanoyloxyalkanoyl residues. 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.

  描述和声明了一种作为辅助剂和免疫效应物的氨基糖脂磷酸酯（AGP）化合物。这些化合物具有一个2-脱氧-2-氨基葡萄糖与一个氨基烷基（糖苷）基团的糖苷键连接。这些化合物在葡萄糖氨基环上的4或6碳上磷酸化，并包括三个3-烷酰氧烷酰基。这些化合物增强了免疫动物中的抗体产生，同时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辅助剂和免疫效应物的组合物和方法。
• Synthesis and biological evaluation of a new class of vaccine adjuvants: aminoalkyl glucosaminide 4-phosphates (AGPs)
  作者：David A. Johnson、C. Gregory Sowell、Craig L. Johnson、Mark T. Livesay、David S. Keegan、Michael J. Rhodes、J. Terry Ulrich、Jon R. Ward、John L. Cantrell、Valerie G. Brookshire

  DOI：10.1016/s0960-894x(99)00374-1

  日期：1999.8

  A novel series of acylated omega-aminoalkyl 2-amino-2-deoxy-4-phosphono-beta-D-glucopyranosides (aminoalkyl glucosaminide 4-phosphates) was synthesized and screened for immunostimulant activity. Several of these compounds enhance the production of tetanus toroid-specific antibodies in mice and augment vaccine-induced cytotoxic T cells against EG.7-ova target cells. (C) 1999 Elsevier Science Ltd. Pill rights reserved.
• US6303347B1
  申请人：——

  公开号：US6303347B1

  公开（公告）日：2001-10-16
• The ‘Ethereal’ nature of TLR4 agonism and antagonism in the AGP class of lipid A mimetics
  作者：Hélène G. Bazin、Tim J. Murray、William S. Bowen、Afsaneh Mozaffarian、Steven P. Fling、Laura S. Bess、Mark T. Livesay、Jeffrey S. Arnold、Craig L. Johnson、Kendal T. Ryter、Christopher W. Cluff、Jay T. Evans、David A. Johnson

  DOI：10.1016/j.bmcl.2008.09.060

  日期：2008.10

  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.