3-{6-methyl-3-oxo-4-[3-(trifluoromethyl)phenyl]-3.6-dihydrodipyrazolo[3,4-b:3.4-d]pyridin-2(1H)-yl}benzoic acid | 635325-27-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-{6-methyl-3-oxo-4-[3-(trifluoromethyl)phenyl]-3.6-dihydrodipyrazolo[3,4-b:3.4-d]pyridin-2(1H)-yl}benzoic acid
• 英文别名: 3-[10-Methyl-5-oxo-7-[3-(trifluoromethyl)phenyl]-3,4,8,10,11-pentazatricyclo[7.3.0.02,6]dodeca-1,6,8,11-tetraen-4-yl]benzoic acid
• CAS: 635325-27-8
• 化学式: C₂₂H₁₄F₃N₅O₃
• 分子量: 453.38
• InChiKey: ZWRQPEWYISPCJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-(氨基甲基)-2-甲氧基苯酚盐酸盐 、 3-{6-methyl-3-oxo-4-[3-(trifluoromethyl)phenyl]-3.6-dihydrodipyrazolo[3,4-b:3.4-d]pyridin-2(1H)-yl}benzoic acid 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以45%的产率得到N-[(4-hydroxy-3-methoxyphenyl)methyl]-3-[10-methyl-5-oxo-7-[3-(trifluoromethyl)phenyl]-3,4,8,10,11-pentazatricyclo[7.3.0.02,6]dodeca-1,6,8,11-tetraen-4-yl]benzamide
  参考文献：
  名称：

  Structure–activity studies of a series of dipyrazolo[3,4- b :3′,4′- d ]pyridin-3-ones binding to the immune regulatory protein B7.1

  摘要：

  The interaction of co-stimulatory molecules on T cells with 137 molecules on antigen presenting cells plays an important role in the activation of naive T cells. Consequently, agents that disrupt these interactions should have applications in treatment of transplant rejection as well as autoimmune diseases. To this end, specific small molecule inhibitors of human B7.1 were identified and characterized. Herein, we report the identification of potent small molecule inhibitors of the B7.1-CD28 interaction. In a high-throughput screen we identified several leads that prevented the interaction of B7.1 with CD28 with activities in the nanomolar to low micromolar range. One of these, the dihydrodipyrazolopyridinone 1, was subsequently shown to bind the V-like domain of human B7.1 at equimolar stoichiometry. With this as a starting point, we report here the synthesis and initial in vitro structure-activity relationships of a series of these compounds. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00183-4
• 作为产物：
  描述：

  5-氨基-1-甲基吡唑-4-甲酸乙酯 在 sodium hydride 、 sodium t-butanolate 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙二醇 为溶剂， 反应 22.0h， 生成 3-{6-methyl-3-oxo-4-[3-(trifluoromethyl)phenyl]-3.6-dihydrodipyrazolo[3,4-b:3.4-d]pyridin-2(1H)-yl}benzoic acid
  参考文献：
  名称：

  Structure–activity studies of a series of dipyrazolo[3,4- b :3′,4′- d ]pyridin-3-ones binding to the immune regulatory protein B7.1

  摘要：

  The interaction of co-stimulatory molecules on T cells with 137 molecules on antigen presenting cells plays an important role in the activation of naive T cells. Consequently, agents that disrupt these interactions should have applications in treatment of transplant rejection as well as autoimmune diseases. To this end, specific small molecule inhibitors of human B7.1 were identified and characterized. Herein, we report the identification of potent small molecule inhibitors of the B7.1-CD28 interaction. In a high-throughput screen we identified several leads that prevented the interaction of B7.1 with CD28 with activities in the nanomolar to low micromolar range. One of these, the dihydrodipyrazolopyridinone 1, was subsequently shown to bind the V-like domain of human B7.1 at equimolar stoichiometry. With this as a starting point, we report here the synthesis and initial in vitro structure-activity relationships of a series of these compounds. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00183-4

文献信息

• Dihydrodipyrazolopyridinylbenzamide and -sulfonamide inhibitors of B7-1
  申请人：Wyeth

  公开号：US20040024008A1

  公开（公告）日：2004-02-05

  The present invention provides a compound of formula I and the use thereof for the immunotherapeutic treatment of transplant rejection or autoimmune disease. 1

  本发明提供了一种化合物I的公式以及其用于免疫治疗移植排斥或自身免疫疾病的用途。
• US6734190B2
  申请人：——

  公开号：US6734190B2

  公开（公告）日：2004-05-11
• Structure–activity studies of a series of dipyrazolo[3,4- b :3′,4′- d ]pyridin-3-ones binding to the immune regulatory protein B7.1
  作者：Neal J. Green、Jason Xiang、Jing Chen、Lihren Chen、Audrey M. Davies、Dave Erbe、Steve Tam、James F. Tobin

  DOI：10.1016/s0968-0896(03)00183-4

  日期：2003.7

  The interaction of co-stimulatory molecules on T cells with 137 molecules on antigen presenting cells plays an important role in the activation of naive T cells. Consequently, agents that disrupt these interactions should have applications in treatment of transplant rejection as well as autoimmune diseases. To this end, specific small molecule inhibitors of human B7.1 were identified and characterized. Herein, we report the identification of potent small molecule inhibitors of the B7.1-CD28 interaction. In a high-throughput screen we identified several leads that prevented the interaction of B7.1 with CD28 with activities in the nanomolar to low micromolar range. One of these, the dihydrodipyrazolopyridinone 1, was subsequently shown to bind the V-like domain of human B7.1 at equimolar stoichiometry. With this as a starting point, we report here the synthesis and initial in vitro structure-activity relationships of a series of these compounds. (C) 2003 Elsevier Science Ltd. All rights reserved.