methyl (2S)-2-[[(2R)-2-amino-3-[2-(4-tridecyltriazol-1-yl)ethylsulfanyl]propanoyl]amino]-3-hydroxypropanoate

• 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: methyl (2S)-2-[[(2R)-2-amino-3-[2-(4-tridecyltriazol-1-yl)ethylsulfanyl]propanoyl]amino]-3-hydroxypropanoate
• 化学式: C₂₄H₄₅N₅O₄S
• 分子量: 499.718
• InChiKey: YJPURCMTOHPPGG-VXKWHMMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  34
• 可旋转键数：
  22
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  158
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-[[(2R)-2-amino-3-[2-(4-tridecyltriazol-1-yl)ethylsulfanyl]propanoyl]amino]-3-hydroxypropanoate 、 乙酸酐 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (S)-methyl 2-((R)-2-acetamido-3-((2-(4-tridecyl-1H-1,2,3-triazol-1-yl)ethyl)thio)propanamido)-3-hydroxypropanoate
  参考文献：
  名称：

  Design and Development of Stable, Water-Soluble, Human Toll-like Receptor 2 Specific Monoacyl Lipopeptides as Candidate Vaccine Adjuvants

  摘要：

  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.

  DOI：

  10.1021/jm400620g
• 作为产物：
  描述：

  (S)-methyl 2-((R)-3-((2-azidoethyl)thio)-2-((tert-butoxycarbonyl)amino)propanamido)-3-(tert-butoxy)propanoate 在 copper(ll) sulfate pentahydrate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 0.5h， 生成 methyl (2S)-2-[[(2R)-2-amino-3-[2-(4-tridecyltriazol-1-yl)ethylsulfanyl]propanoyl]amino]-3-hydroxypropanoate
  参考文献：
  名称：

  Design and Development of Stable, Water-Soluble, Human Toll-like Receptor 2 Specific Monoacyl Lipopeptides as Candidate Vaccine Adjuvants

  摘要：

  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.

  DOI：

  10.1021/jm400620g

文献信息

• [EN] TOLL-LIKE RECEPTOR 2-AGONISTIC LIPOPEPTIDES, AND METHOD OF MAKING THE SAME<br/>[FR] LIPOPEPTIDES AGONISTES DU RÉCEPTEUR 2 DE TYPE TOLL, ET PROCÉDÉ DE FABRICATION DE CEUX-CI
  申请人：UNIV KANSAS

  公开号：WO2014113634A1

  公开（公告）日：2014-07-24

  The present disclosure is directed to a novel class of toll-like receptor 2-agnonistic (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。
• 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。
• US9676818B2
  申请人：——

  公开号：US9676818B2

  公开（公告）日：2017-06-13