(4R,7R,8aR)-1'-[3-[[2-(4-chlorophenoxy)acetyl]amino]-1H-1,2,4-triazole-5-carbonyl]-6-oxospiro[3,4,8,8a-tetrahydro-2H-pyrrolo[2,1-b][1,3]thiazine-7,2'-pyrrolidine]-4-carboxamide | 894787-32-7

• 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: (4R,7R,8aR)-1'-[3-[[2-(4-chlorophenoxy)acetyl]amino]-1H-1,2,4-triazole-5-carbonyl]-6-oxospiro[3,4,8,8a-tetrahydro-2H-pyrrolo[2,1-b][1,3]thiazine-7,2'-pyrrolidine]-4-carboxamide
• CAS: 894787-32-7
• 化学式: C₂₂H₂₄ClN₇O₅S
• 分子量: 533.995
• InChiKey: KBOCGSHLUJBKCF-VKIFBMEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  189
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-1H-1,2,4-triazole-3-carboxylic acid 、 (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 、 4-氯苯氧基乙酰氯 以1.3 mg的产率得到(4R,7R,8aR)-1'-[3-[[2-(4-chlorophenoxy)acetyl]amino]-1H-1,2,4-triazole-5-carbonyl]-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

文献信息

• Myd88 Homodimerization Inhibitors
  申请人：Carminati Paolo

  公开号：US20080064643A1

  公开（公告）日：2008-03-13

  The present invention relates to peptidic and peptidomimetic compounds with the formula (X − )AA 1 -AA 2 -AA 3 -AA 4 -AA 5 -AA 6 -AA 7 in which the various groups are defined in the description here below, which mimic a particular protein portion of MyD88, preventing its homodimerisation and interfering with its interaction with the TIR domain. The present invention also provides procedures for the preparation of said compounds, pharmaceutical compositions containing them and their use as medicaments, particularly for the treatment of inflammatory and autoimmune diseases.
• 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.