4-(6-methyl-3-oxo-4-(3-(trifluoromethyl)phenyl)-3,6-dihydrodipyrazolo[3,4-b:3',4'-d]pyridin-2(1H)-yl)benzoic acid | 635324-87-7

• 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: 4-(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: 4-[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: 635324-87-7
• 化学式: C₂₂H₁₄F₃N₅O₃
• 分子量: 453.38
• InChiKey: HYWGLFWNLHFOSD-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-(6-methyl-3-oxo-4-(3-(trifluoromethyl)phenyl)-3,6-dihydrodipyrazolo[3,4-b:3',4'-d]pyridin-2(1H)-yl)benzoic acid 在 硼烷 作用下， 以 四氢呋喃 为溶剂， 以55%的产率得到2-[4-(hydroxymethyl)phenyl]-6-methyl-4-[3-(trifluoromethyl)phenyl]-1,6-dihydrodipyrazolo[3,4-b:3',4'-d]pyridin-3(2H)-one
  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 四氢呋喃 、 乙二醇 为溶剂， 反应 19.5h， 生成 4-(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：

  正电子发射断层扫描成像人CD80的小分子的合成和结构亲和关系。

  摘要：

  共刺激分子CD80是免疫激活的早期标记。它在活化的抗原呈递细胞上调。我们旨在开发一种通过正电子发射断层扫描（PET）对CD80成像的示踪剂。合成了新型CD80配体，并通过SPR测试了对人CD80（hCD80）的亲和力和内源性配体的置换。几种化合物以1纳摩尔的亲和力与hCD80结合，并以纳摩尔浓度取代了CTLA-4和CD28。结构亲和关系研究揭示了与hCD80的强亲和力相关的部分，以及进一步修饰的位置。铅化合物MT107（7f）被碳11放射性标记。在体外，[11C] MT107显示出与hCD80阳性组织的特异性结合和高血浆蛋白结合。在体内，[11C] MT107积累在肝脏，胆囊，和肠道，但很少出现在hCD80阳性异种移植物中。高血浆蛋白结合和广泛的胆汁排泄可能导致不利的体内性能。

  DOI：

  10.1021/acs.jmedchem.9b00858

文献信息

• 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.
• Synthesis and Structure–Affinity Relationship of Small Molecules for Imaging Human CD80 by Positron Emission Tomography
  作者：Marco F. Taddio、Linjing Mu、Claudia A. Castro Jaramillo、Tanja Bollmann、Dominik M. Schmid、Lukas P. Muskalla、Tim Gruene、Aristeidis Chiotellis、Simon M. Ametamey、Roger Schibli、Stefanie D. Krämer

  DOI：10.1021/acs.jmedchem.9b00858

  日期：2019.9.12

  tracer for imaging CD80 by positron emission tomography (PET). Novel CD80 ligands were synthesized and tested by SPR for affinity to human CD80 (hCD80) and displacement of endogenous ligands. Several compounds bound with one-digit nanomolar affinity to hCD80 and displaced CTLA-4 and CD28 at nanomolar concentrations. A structure-affinity relationship study revealed relevant moieties for strong affinity to

  共刺激分子CD80是免疫激活的早期标记。它在活化的抗原呈递细胞上调。我们旨在开发一种通过正电子发射断层扫描（PET）对CD80成像的示踪剂。合成了新型CD80配体，并通过SPR测试了对人CD80（hCD80）的亲和力和内源性配体的置换。几种化合物以1纳摩尔的亲和力与hCD80结合，并以纳摩尔浓度取代了CTLA-4和CD28。结构亲和关系研究揭示了与hCD80的强亲和力相关的部分，以及进一步修饰的位置。铅化合物MT107（7f）被碳11放射性标记。在体外，[11C] MT107显示出与hCD80阳性组织的特异性结合和高血浆蛋白结合。在体内，[11C] MT107积累在肝脏，胆囊，和肠道，但很少出现在hCD80阳性异种移植物中。高血浆蛋白结合和广泛的胆汁排泄可能导致不利的体内性能。