2-(((R)-2-acetamido-3-(((S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl)amino)-3-oxopropyl)thio)ethyl palmitate | 1365683-20-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(((R)-2-acetamido-3-(((S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl)amino)-3-oxopropyl)thio)ethyl palmitate
• 英文别名: 2-(((2R)-2-acetamido-3-(((2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl)amino)-3-oxopropyl)thio)ethyl palmitate；2-[(2R)-2-acetamido-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl hexadecanoate
• CAS: 1365683-20-0
• 化学式: C₂₇H₅₀N₂O₇S
• 分子量: 546.769
• InChiKey: SYGMCNJPAMYJBB-ZEQRLZLVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  37
• 可旋转键数：
  26
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  156
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(((R)-2-acetamido-3-(((S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl)amino)-3-oxopropyl)thio)ethyl palmitate 在 吡啶 、 三氧化硫吡啶 作用下， 反应 16.0h， 以100%的产率得到2-(((R)-2-acetamido-3-(((S)-1-methoxy-1-oxo-3-(sulfooxy)propan-2-yl)amino)-3-oxopropyl)thio)ethyl palmitate
  参考文献：
  名称：

  [EN] TOLL-LIKE RECEPTOR 2-AGONISTIC LIPOPEPTIDES, AND METHOD OF MAKING THE SAME
  [FR] LIPOPEPTIDES AGONISTES DU RÉCEPTEUR 2 DE TYPE TOLL, ET PROCÉDÉ DE FABRICATION DE CEUX-CI

  摘要：

  本公开涉及一类新型的特定结构的类胜肽化的类Toll样受体2激动剂（TLR2）脂肽化合物，以及制备这些化合物的合成方法。这些化合物在人类TLR2中具有高激动活性，并可用作疫苗佐剂。疫苗可能是针对传染病最成功的医学干预之一。

  公开号：

  WO2014113634A1
• 作为产物：
  描述：

  2-(((R)-3-(((S)-3-(tert-butoxy)-1-methoxy-1-oxopropan-2-yl)amino)-2-(tert-butoxycarbonylamino)-3-oxopropyl)thio)ethyl palmitate 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-(((R)-2-acetamido-3-(((S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl)amino)-3-oxopropyl)thio)ethyl palmitate
  参考文献：
  名称：

  Structure–Activity Relationships in Human Toll-like Receptor 2-Specific Monoacyl Lipopeptides

  摘要：

  Toll-like receptor 2-agonistic lipopeptides typified by S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-R-cysteinyl-S-serine (PAM(2)CS) compounds are potential vaccine adjuvants. We had previously determined that at least one acyl group of optimal length (C-16) and an appropriately orientated ester carbonyl group is essential for TLR2-agonistic activity. We now show that these structurally simpler analogues display agonistic activities with human, but not murine, TLR2. SAR studies on the monoacyl derivatives show that the optimal acyl chain length is C-16, and aryl substituents are not tolerated. A variety of alkyl and acyl substituents on the cysteine amine were examined. All N-alkyl derivatives were inactive. In contradistinction, short-chain N-acyl analogues were found to be highly active, with a clear dependence on the chain length. A cysteine N-acetyl analogue was found to be the most potent (EC50: 1 nM), followed by the N-butyryl analogue. The N-acetyl analogue is human TLR2-specific, with its potency comparable to that of PAM(2)CS.

  DOI：

  10.1021/jm3000533

文献信息

• Simplified Monopalmitoyl Toll‐like Receptor 2 Ligand Mini‐UPam for Self‐Adjuvanting Neoantigen‐Based Synthetic Cancer Vaccines
  作者：Thomas C. Ende、Jeroen M. M. Heuts、Geoffroy P. P. Gential、Marten Visser、Michel J. Graaff、Nataschja I. Ho、Wim Jiskoot、A. Rob P. M. Valentijn、Nico J. Meeuwenoord、Herman S. Overkleeft、Jeroen D. C. Codée、Sjoerd H. Burg、Els M. E. Verdegaal、Gijsbert A. Marel、Ferry Ossendorp、Dmitri V. Filippov

  DOI：10.1002/cbic.202000687

  日期：2021.4.6

  Less lipophilic ligands: A novel TLR2 ligand has been designed and synthesized to be subsequently conjugated with synthetic peptides containing clinically relevant neoepitopes. By treating HEK‐TLR2 cells, human moDCs and antigen specific human T‐cells with these new constructs, the immunogenic potential of the new TLR2 ligand and the conjugation of TLR ligands with neoepitopes was assessed.

  亲脂性较低的配体：设计并合成了一种新型 TLR2 配体，随后与含有临床相关新表位的合成肽缀合。通过用这些新构建体处理 HEK-TLR2 细胞、人类 moDC 和抗原特异性人类 T 细胞，评估了新 TLR2 配体的免疫原性潜力以及 TLR 配体与新表位的结合。
• TOLL-LIKE RECEPTOR 2-AGONISTIC LIPOPEPTIDES, AND METHOD OF MAKING THE SAME
  申请人：UNIVERSITY OF KANSAS

  公开号：US20150337009A1

  公开（公告）日：2015-11-26

  The present disclosure is directed to a novel class of toll-like receptor 2-agonistic (TLR2) lipopeptide compounds having specific structures, and synthetic methods of making the compounds. These compounds provide high potency of agonistic activities with human, other than murine, TLR2, and are useful as vaccine adjuvants. Vaccines are perhaps one of the most successful medical interventions against infectious disease.

  本公开涉及一种新型的具有特定结构的Toll样受体2-激动剂（TLR2）脂肽化合物及其合成方法。这些化合物在人类（而非小鼠）的TLR2上具有高效的激动活性，并可用作疫苗佐剂。疫苗可能是预防传染病最成功的医疗干预措施之一。
• Design and Development of Stable, Water-Soluble, Human Toll-like Receptor 2 Specific Monoacyl Lipopeptides as Candidate Vaccine Adjuvants
  作者：Deepak B. Salunke、Seth W. Connelly、Nikunj M. Shukla、Alec R. Hermanson、Lauren M. Fox、Sunil A. David

  DOI：10.1021/jm400620g

  日期：2013.7.25

  Antigens in modern subunit vaccines are largely soluble and poorly immunogenic proteins inducing relatively short-lived immune responses. Appropriate adjuvants initiate early innate immune responses, amplifying subsequent adaptive immune responses. Agonists of Toll-like receptor 2 (TLR2) are devoid of significant proinflammatory activity in ex vivo human blood models and yet are potently adjuvantic, suggesting that this chemotype may be a safe and effective adjuvant. Our earlier work on the monoacyl lipopeptide class of TLR2 agonists led to the design of a highly potent lead but with negligible aqueous solubility, necessitating the reintroduction of aqueous solubility. We explored several strategies of introducing ionizable groups on the lipopeptide, as well as the systematic evaluation of chemically stable bioisosteres of the ester-linked palmitoyl group. These studies have led to a fully optimized, chemically stable, and highly water-soluble human TLR2-specific agonist, which was found to have an excellent safety profile and displayed prominent adjuvantic activities in rabbit models.
• US9676818B2
  申请人：——

  公开号：US9676818B2

  公开（公告）日：2017-06-13