N-[4-(3,4-difluorophenyl)thiazol-2-yl]-4-[2,4-dioxothiazolidin-(5Z)-ylidenemethyl]benzamide | 1026923-05-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[4-(3,4-difluorophenyl)thiazol-2-yl]-4-[2,4-dioxothiazolidin-(5Z)-ylidenemethyl]benzamide
• 英文别名: (Z)-N-(4-(3,4-difluorophenyl)thiazol-2-yl)-4-((2,4-dioxothiazolidin-5-ylidene)methyl)benzamide；N-[4-(3,4-difluorophenyl)-1,3-thiazol-2-yl]-4-[(Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]benzamide
• CAS: 1026923-05-6
• 化学式: C₂₀H₁₁F₂N₃O₃S₂
• 分子量: 443.454
• InChiKey: XANYDTDNPVDRJP-APSNUPSMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  142
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-(5-(三氟甲基)-1,3,4-噻唑-2-基)哌嗪 、 4-(2,4-dioxothiazolidin-5-ylidenemethyl)benzoic acid 生成 N-[4-(3,4-difluorophenyl)thiazol-2-yl]-4-[2,4-dioxothiazolidin-(5Z)-ylidenemethyl]benzamide
  参考文献：
  名称：

  Characterization of novel non-peptide thrombopoietin mimetics, their species specificity and the activation mechanism of the thrombopoietin receptor

  摘要：

  A series of non-peptide small compounds discovered to be thrombopoietin receptor agonists showed species specificity to humans. Compound I could induce megakaryocyte lineage from human bone marrow cells, but not from mouse, guinea pig or cynomolgus monkey bone marrow cells. To elucidate the mechanism, we identified the pivotal amino acid residue for the receptor activation by compound I by taking advantage of its species specificity. The response of compound I to three human/mouse chimeric receptors indicated the importance of the transmembrane domain. Comparison of amino acid sequences of the transmembrane domain of the thrombopoietin receptor between human and three animal species led us to hypothesize that histidine 499 is necessary for the reactivity to the thrombopoietin mimetics. We verified the hypothesis using two mutant receptors: the human thrombopoietin receptor mutant His499Leu and the mouse thrombopoietin receptor mutant Leu490His. These results should be helpful for structure-activity relationship studies and conducting in vivo studies of thrombopoietin mimetics. (C) 2008 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejphar.2008.02.060

文献信息

• Characterization of novel non-peptide thrombopoietin mimetics, their species specificity and the activation mechanism of the thrombopoietin receptor
  作者：Noriko Yamane、Yoshikazu Tanaka、Naoki Ohyabu、Shoji Yamane、Kazuhiko Maekawa、Jun Ishizaki、Ryuji Suzuki、Tsunetoshi Itoh、Hiroshi Takemoto

  DOI：10.1016/j.ejphar.2008.02.060

  日期：2008.5

  A series of non-peptide small compounds discovered to be thrombopoietin receptor agonists showed species specificity to humans. Compound I could induce megakaryocyte lineage from human bone marrow cells, but not from mouse, guinea pig or cynomolgus monkey bone marrow cells. To elucidate the mechanism, we identified the pivotal amino acid residue for the receptor activation by compound I by taking advantage of its species specificity. The response of compound I to three human/mouse chimeric receptors indicated the importance of the transmembrane domain. Comparison of amino acid sequences of the transmembrane domain of the thrombopoietin receptor between human and three animal species led us to hypothesize that histidine 499 is necessary for the reactivity to the thrombopoietin mimetics. We verified the hypothesis using two mutant receptors: the human thrombopoietin receptor mutant His499Leu and the mouse thrombopoietin receptor mutant Leu490His. These results should be helpful for structure-activity relationship studies and conducting in vivo studies of thrombopoietin mimetics. (C) 2008 Elsevier B.V. All rights reserved.