6-(2,6-二甲基苯基)-吡啶并[2,3-d]嘧啶-2,7-二胺 | 179343-59-0

• 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
• 中文名称: 6-(2,6-二甲基苯基)-吡啶并[2,3-d]嘧啶-2,7-二胺
• 英文名称: 2,7-diamino-6-(2,6-dimethylphenyl)-pyrido[2,3-d]pyrimidine
• 英文别名: 2,7-diamino-6-(2,6-dimethylphenyl)pyrido[2,3-d]pyrimidine；6-(2,6-Dimethylphenyl)pyrido[2,3-d]pyrimidine-2,7-diamine
• CAS: 179343-59-0
• 化学式: C₁₅H₁₅N₅
• 分子量: 265.318
• InChiKey: LSHICSIXTRDLPS-UHFFFAOYSA-N

物化性质

• 沸点：
  474.3±55.0 °C(Predicted)
• 密度：
  1.290±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  90.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(2,6-二甲基苯基)-吡啶并[2,3-d]嘧啶-2,7-二胺 生成 1-[2-amino-6-(2,6-dimethylphenyl)-pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea
  参考文献：
  名称：

  6-Aryl pyrido\x9b2,3-d! pyrimidines and naphthyridines for inhibiting

  摘要：

  6-芳基吡啶并[2,3-d]嘧啶和萘嘧啶是蛋白酪氨酸激酶的抑制剂，因此在治疗由此介导的细胞增殖方面非常有用。这些化合物在治疗动脉粥样硬化、再狭窄、牛皮癣以及细菌感染方面特别有用。

  公开号：

  US05733913A1
• 作为产物：
  描述：

  2,4-二氨基嘧啶-5-甲醛 、 2,6-二甲基苯乙腈 在 sodium hydride 作用下， 以 乙二醇乙醚 为溶剂， 反应 4.0h， 以32%的产率得到6-(2,6-二甲基苯基)-吡啶并[2,3-d]嘧啶-2,7-二胺
  参考文献：
  名称：

  一系列新型的吡啶并[2,3-d]嘧啶酪氨酸激酶抑制剂的构效关系。

  摘要：

  化合物库中成纤维细胞生长因子（FGFr）和血小板衍生生长因子（PDGFr）受体酪氨酸激酶抑制剂的筛选导致了一系列新型的ATP竞争性吡啶并[2,3-d]嘧啶酪氨酸激酶抑制剂。发现了最初的铅1- [2-氨基-6-（2,6-二氯苯基）吡啶基[2,3-d]嘧啶-7-基] -3-叔丁基脲（4b，PD-089828）成为广泛活性的酪氨酸激酶抑制剂。化合物4b抑制PDGFr，FGFr，EGFr和c-src酪氨酸激酶，IC50值分别为1.11、0.13、0.45和0.22 microM。随后的SAR研究导致合成了新的类似物，相对于最初的铅，这些类似物的效能，溶解度和生物利用度均得到了改善。例如，将[4-（二乙基氨基）丁基]氨基侧链引入4b的2-位得到具有增强的效能和生物利用度的化合物6c。化合物6c抑制PDGF刺激的血管平滑肌细胞增殖，IC50为0.3 microM。此外，用6-（3'，5'-二甲氧基苯基）官能团代替4b的6-（2

  DOI：

  10.1021/jm970367n

文献信息

• Soluble 2-Substituted Aminopyrido[2,3-<i>d</i>]pyrimidin-7-yl Ureas. Structure−Activity Relationships against Selected Tyrosine Kinases and Exploration of in Vitro and in Vivo Anticancer Activity
  作者：Mel C. Schroeder、James M. Hamby、Cleo J. C. Connolly、Patrick J. Grohar、R. Thomas Winters、Mark R. Barvian、Charles W. Moore、Stacey L. Boushelle、Sheila M. Crean、Alan J. Kraker、Denise L. Driscoll、Patrick W. Vincent、William L. Elliott、Gina H. Lu、Brian L. Batley、Tawny K. Dahring、Terry C. Major、Robert L. Panek、Annette M. Doherty、H. D. Hollis Showalter

  DOI：10.1021/jm0004291

  日期：2001.6.1

  continuing our search for medicinal agents to treat proliferative diseases, we have discovered 2-substituted aminopyrido[2,3-d]pyrimidin-7-yl ureas as a novel class of soluble, potent, broadly active tyrosine kinase (TK) inhibitors. An efficient route was developed that enabled the synthesis of a wide variety of analogues with substitution on several positions of the template. From the lead structure 1, several series of analogues were made that examined the C-6 aryl substituent, a variety of water solublizing substitutents at the C-2 position, and urea or other acyl functionality at the N-7 position. Compounds of this series were competitive with ATP and displayed submicromolar to low nanomolar potency against a panel of TKs, including receptor (platelet-derived growth factor, PDGFr; fibroblast growth factor, FGFr;) and nonreceptor (c-Src) classes. Several of the most potent compounds displayed submicromolar inhibition of PDGF-mediated receptor autophosphorylation in rat aortic vascular smooth muscle cells and low micromolar inhibition of cellular growth in five human tumor cell lines. One of the more thoroughly evaluated members, 32, with IC50 values of 0.21 muM (PDGFr), 0.049 muM (bFGFr), and 0.018 muM (c-Src), was evaluated in in vivo studies against a panel of five human tumor xenografts, with known and/or inferred dependence on the EGFr, PDGFr, and c-Src TKs. Compound 32 produced a tumor growth delay of 14 days against the Cole-205 colon xenograft model.
• Discovery and structure-activity studies of a novel series of pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors
  作者：Cleo J.C. Connolly、James M. Hamby、Mel C. Schroeder、Mark Barvian、Gina H. Lu、Robert L. Panek、Aneesa Amar、Cindy Shen、Alan J. Kraker、David W. Fry、Wayne D. Klohs、Annette M. Doherty

  DOI：10.1016/s0960-894x(97)00445-9

  日期：1997.9

  The inhibition of tyrosine kinase-mediated signal transduction pathways represents a therapeutic approach to the intervention of proliferative diseases such as cancer, atherosclerosis, and restenosis. A novel series of pyrido[2,3-d]pyrimidine inhibitors of the PDGFr, bFGFr, and c-Src tyrosine kinases was developed from compound library screening and lead optimization.(1) In addition, highly selective inhibitors of the FGFr tyrosine kinase were also discovered and developed from this novel series of pyrido[2,3-d]pyrimidines. The syntheses, biological evaluation, and structure-activity relationships of this series are reported. (C) 1997 Elsevier Science Ltd.
• 6-ARYL PYRIDO( 2,3-d]PYRIMIDINES AND NAPHTHYRIDINES FOR INHIBITING PROTEIN TYROSINE KINASE MEDIATED CELLULAR PROLIFERATION
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0790997A2

  公开（公告）日：1997-08-27
• 6-ARYL PYRIDO[2,3-d]PYRIMIDINES AND NAPHTHYRIDINES FOR INHIBITING PROTEIN TYROSINE KINASE MEDIATED CELLULAR PROLIFERATION
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0790997B1

  公开（公告）日：2000-03-22
• US5952342A
  申请人：——

  公开号：US5952342A

  公开（公告）日：1999-09-14