2-(2-(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl)ethoxy)acetic acid | 1332360-36-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 2-(2-(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl)ethoxy)acetic acid
• CAS: 1332360-36-7
• 化学式: C₁₁H₁₁NO₆S
• 分子量: 285.277
• InChiKey: FQVYTUUUEYIRJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.07
• 重原子数：
  19.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  100.98
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-(2-(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl)ethoxy)acetic acid 、 L-alanyl-D-isoglutamine benzyl ester trifluoroacetate 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以88%的产率得到benzyl (4R)-5-amino-5-oxo-4-{[(2S)-2-({2-[2-(1,1,3-trioxo-1,3-dihydro-2H-1,2-benzisothiazol-2-yl)ethoxy]acetyl}amino)propanoyl]amino}pentanoate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel desmuramyldipeptide analogs

  摘要：

  A series of novel desmuramyldipeptides have been designed and synthesized as part of our search for therapeutically useful muramyldipeptide (MOP) analogs. Their immunomodulatory properties were initially assessed in vitro, evaluating their effect on lipopolysaccharide (LPS)-induced cytokine release in THP-1 cells. Following the initial screening, selected compounds were further investigated for immunomodulatory properties using LPS and phorbol 12-myristate 13-acetate (PMA)/ionomycin-stimulated human peripheral blood mononuclear cells. The results confirmed the immunomodulatory properties of some of the synthesized desmuramyldipeptide analogs. Taken together, presented data confirmed the immunostimulatory effect of compound 44, MDP derivative incorporating a pyrido-fused [1,2]-benzisothiazole moiety, while for compounds 32 and 39, indole scaffold-based derivatives of MOP, an immunosuppressive effect was observed. Further studies will be necessary to address their potential therapeutic use as immunomodulatory drugs, both as immunostimulants or anti-inflammatory agents. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.042

文献信息

• Immunomodulatory Properties of Novel Nucleotide Oligomerization Domain 2 (Nod2) Agonistic Desmuramyldipeptides
  作者：Žiga Jakopin、Martina Gobec、Irena Mlinarič-Raščan、Marija Sollner Dolenc

  DOI：10.1021/jm300503b

  日期：2012.7.26

  There is a pressing need for the development of novel adjuvants for human use. The minimal bioactive structure of bacterial peptidoglycan (PGN), muramyldipeptide (MDP), and its derivative murabutide (MB) have long been known for their adjuvant activities. For this reason, a series of novel desmuramyldipepticles have been designed and synthesized as part of our search for therapeutically useful MDP analogues. Since nucleotide oligomerization domain 2 (Nod2) is a putative receptor for MDP, we used engineered HEK293 cells overexpressing Nod2 to screen and validate our compounds for their Nod2-agonist activity. Their immunomodulatory properties were subsequently assessed in vitro by evaluating their effect on proinflammatory cytolcine production of phorbol 12-myristate 13-acetate (PMA)/ionomycin-stimulated human peripheral blood mononuclear cells (PBMCs). Herein, we present novel desmuramyldipeptides, the most active of them possessing immunoenhancing properties as a result of their potent Nod2-agonistic effect.