(2R,4'R,8a'R)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-6'-oxotetrahydro-2'H-spiro[pyrrolidine-2,7'-pyrrole[2,1-b][1,3]thiazine]-4'-carboxylic acid | 894786-97-1

• 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: (2R,4'R,8a'R)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-6'-oxotetrahydro-2'H-spiro[pyrrolidine-2,7'-pyrrole[2,1-b][1,3]thiazine]-4'-carboxylic acid
• 英文别名: (4R,7R,8aR)-1'-(9H-fluoren-9-ylmethoxycarbonyl)-6-oxospiro[3,4,8,8a-tetrahydro-2H-pyrrolo[2,1-b][1,3]thiazine-7,2'-pyrrolidine]-4-carboxylic acid
• CAS: 894786-97-1
• 化学式: C₂₆H₂₆N₂O₅S
• 分子量: 478.569
• InChiKey: KULNPSKFULYNHA-XLGIIRLISA-N

物化性质

• 熔点：
  108-115 °C
• 沸点：
  737.7±60.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-甲基吡嗪-2-甲酰氯 、 对氨基苯甲酰-beta-丙氨酸 、 (2R,4'R,8a'R)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-6'-oxotetrahydro-2'H-spiro[pyrrolidine-2,7'-pyrrole[2,1-b][1,3]thiazine]-4'-carboxylic acid 以5.5 mg的产率得到(4R,7R,8aR)-1'-[3-[[4-[(5-methylpyrazine-2-carbonyl)amino]benzoyl]amino]propanoyl]-6-oxospiro[3,4,8,8a-tetrahydro-2H-pyrrolo[2,1-b][1,3]thiazine-7,2'-pyrrolidine]-4-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and In Vitro Activity of Peptidomimetic Inhibitors of Myeloid Differentiation Factor 88

  摘要：

  We describe the design and synthesis of a peptidomimetic library derived from the heptapeptide Ac-RDVLPGT-NH(2), belonging to the Toll/IL-1 receptor (TIR) domain of the adaptor protein MyD88 and effective in inhibiting its homodimerization. The ability of the peptidomimetics to inhibit protein-protein interaction was assessed by yeast 2-hybrid assay and further validated in a mammalian cell system by evaluating the inhibition of NF-kappa B activation, a transcription factor downstream of MyD88 signaling pathway that allows production of essential effector molecules for immune and inflammatory responses.

  DOI：

  10.1021/jm070723u
• 作为产物：
  描述：

  (2R,4'R,8a'R)-4'-carboxy-6'-oxotetrahydro-2'H-spiro[pyrrolidine-2,7'-pyrrolo[2,1-b][1,3]thiazine]trifluoroacetate 、 9-芴甲基-N-琥珀酰亚胺基碳酸酯 在 碳酸氢钠 作用下， 以 水 、 乙酸酐 为溶剂， 反应 20.0h， 以98%的产率得到(2R,4'R,8a'R)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-6'-oxotetrahydro-2'H-spiro[pyrrolidine-2,7'-pyrrole[2,1-b][1,3]thiazine]-4'-carboxylic acid
  参考文献：
  名称：

  Design, Synthesis, and In Vitro Activity of Peptidomimetic Inhibitors of Myeloid Differentiation Factor 88

  摘要：

  We describe the design and synthesis of a peptidomimetic library derived from the heptapeptide Ac-RDVLPGT-NH(2), belonging to the Toll/IL-1 receptor (TIR) domain of the adaptor protein MyD88 and effective in inhibiting its homodimerization. The ability of the peptidomimetics to inhibit protein-protein interaction was assessed by yeast 2-hybrid assay and further validated in a mammalian cell system by evaluating the inhibition of NF-kappa B activation, a transcription factor downstream of MyD88 signaling pathway that allows production of essential effector molecules for immune and inflammatory responses.

  DOI：

  10.1021/jm070723u

文献信息

• Design, Synthesis, and In Vitro Activity of Peptidomimetic Inhibitors of Myeloid Differentiation Factor 88
  作者：Nicola Fantò、Grazia Gallo、Andrea Ciacci、Mauro Semproni、Davide Vignola、Marco Quaglia、Valentina Bombardi、Domenico Mastroianni、M. Pia Zibella、Giancarlo Basile、Marica Sassano、Vito Ruggiero、Rita De Santis、Paolo Carminati

  DOI：10.1021/jm070723u

  日期：2008.3.13

  We describe the design and synthesis of a peptidomimetic library derived from the heptapeptide Ac-RDVLPGT-NH(2), belonging to the Toll/IL-1 receptor (TIR) domain of the adaptor protein MyD88 and effective in inhibiting its homodimerization. The ability of the peptidomimetics to inhibit protein-protein interaction was assessed by yeast 2-hybrid assay and further validated in a mammalian cell system by evaluating the inhibition of NF-kappa B activation, a transcription factor downstream of MyD88 signaling pathway that allows production of essential effector molecules for immune and inflammatory responses.