methyl 6-oxo-5,6-dihydrophenanthridine-3-carboxylate | 39180-41-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: methyl 6-oxo-5,6-dihydrophenanthridine-3-carboxylate
• 英文别名: 6-Oxo-5,6-dihydro-phenanthridine-3-carboxylic acid methyl ester；methyl 6-oxo-5H-phenanthridine-3-carboxylate
• CAS: 39180-41-1
• 化学式: C₁₅H₁₁NO₃
• 分子量: 253.257
• InChiKey: VBQPUTKXPMHSTC-UHFFFAOYSA-N

物化性质

• 沸点：
  351.8±21.0 °C(Predicted)
• 密度：
  1.288±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 6-oxo-5,6-dihydrophenanthridine-3-carboxylate 在 sodium hydroxide 作用下， 生成 6-氧代-5H-菲啶-3-羧酸
  参考文献：
  名称：

  Synthesis of substituted 5[H]phenanthridin-6-ones as potent poly(ADP-ribose)polymerase-1 (PARP1) inhibitors

  摘要：

  1-, 2-, 3-, 4-, 8-, or 10-Substituted 5(H)phenanthridin-6-ones were synthesized and found to be potent PARP1 inhibitors. Among the 28 compounds prepared. some showed not only low IC50 values (compound 1b, 10 nM) but also desirable water solubility characteristics. These properties, which are superior to the common PARP1 inhibitors such as benzamides and isoquinolin-1-ones, are essential for potential therapeutic usage. The variety of compounds allows SAR analysis of favored substituents and substituted positions on 5(H)phenanthridin-6-one ring. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00281-5
• 作为产物：
  描述：

  4-碘-3-硝基苯甲酸甲酯 在 镍 、 铜 、 肼 作用下， 以 甲醇 为溶剂， 反应 8.0h， 生成 methyl 6-oxo-5,6-dihydrophenanthridine-3-carboxylate
  参考文献：
  名称：

  Synthesis of substituted 5[H]phenanthridin-6-ones as potent poly(ADP-ribose)polymerase-1 (PARP1) inhibitors

  摘要：

  1-, 2-, 3-, 4-, 8-, or 10-Substituted 5(H)phenanthridin-6-ones were synthesized and found to be potent PARP1 inhibitors. Among the 28 compounds prepared. some showed not only low IC50 values (compound 1b, 10 nM) but also desirable water solubility characteristics. These properties, which are superior to the common PARP1 inhibitors such as benzamides and isoquinolin-1-ones, are essential for potential therapeutic usage. The variety of compounds allows SAR analysis of favored substituents and substituted positions on 5(H)phenanthridin-6-one ring. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00281-5

文献信息

• Discovery and SAR of 5-(3-Chlorophenylamino)benzo[<i>c</i>][2,6]naphthyridine-8-carboxylic Acid (CX-4945), the First Clinical Stage Inhibitor of Protein Kinase CK2 for the Treatment of Cancer
  作者：Fabrice Pierre、Peter C. Chua、Sean E. O’Brien、Adam Siddiqui-Jain、Pauline Bourbon、Mustapha Haddach、Jerome Michaux、Johnny Nagasawa、Michael K. Schwaebe、Eric Stefan、Anne Vialettes、Jeffrey P. Whitten、Ta Kung Chen、Levan Darjania、Ryan Stansfield、Kenna Anderes、Josh Bliesath、Denis Drygin、Caroline Ho、May Omori、Chris Proffitt、Nicole Streiner、Katy Trent、William G. Rice、David M. Ryckman

  DOI：10.1021/jm101251q

  日期：2011.1.27

  bioavailable ATP-competitive inhibitor of protein kinase CK2 in clinical trials for cancer. CK2 has long been considered a prime cancer drug target because of the roles of deregulated and overexpressed CK2 in cancer-promoting prosurvival and antiapoptotic pathways. These biological properties as well as the suitability of CK2’s small ATP binding site for the design of selective inhibitors, led us to fashion

  本文中，我们对CX-4945（25n）的发现进行了编年史，CX-4945是蛋白激酶CK2的一流的，口服可生物利用的ATP竞争性抑制剂，在癌症的临床试验中得到了证实。CK2长期以来一直被认为是主要的癌症药物靶标，因为CK2的失调和过度表达在促进癌症的生存和抗凋亡途径中起着重要的作用。这些生物学特性以及CK2的小ATP结合位点对选择性抑制剂设计的适用性，使我们开发出了新型的癌症治疗剂。导致25n（K i = 0.38 nM）的最优化是通过分子建模指导的，这表明25n的强结合由疏水相互作用，与Lys68形成的离子桥以及与铰链区的氢键结合而成。发现25n具有高度选择性，可跨物种口服生物利用（20-51％），并且在异种移植模型中有效。25n的发现将首次使CK2在人类中具有治疗靶向性。
• Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-<i>N</i>-methylpyridine-2-carboxamide (AZD5305): A PARP1–DNA Trapper with High Selectivity for PARP1 over PARP2 and Other PARPs
  作者：Jeffrey W. Johannes、Amber Balazs、Derek Barratt、Michal Bista、Matthew D. Chuba、Sabina Cosulich、Susan E. Critchlow、Sébastien L. Degorce、Paolo Di Fruscia、Scott D. Edmondson、Kevin Embrey、Stephen Fawell、Avipsa Ghosh、Sonja J. Gill、Anders Gunnarsson、Sudhir M. Hande、Tom D. Heightman、Paul Hemsley、Giuditta Illuzzi、Jordan Lane、Carrie Larner、Elisabetta Leo、Lina Liu、Andrew Madin、Scott Martin、Lisa McWilliams、Mark J. O’Connor、Jonathan P. Orme、Fiona Pachl、Martin J. Packer、Xiaohui Pei、Andrew Pike、Marianne Schimpl、Hongyao She、Anna D. Staniszewska、Verity Talbot、Elizabeth Underwood、Jeffrey G. Varnes、Lin Xue、Tieguang Yao、Ke Zhang、Andrew X. Zhang、Xiaolan Zheng

  DOI：10.1021/acs.jmedchem.1c01012

  日期：2021.10.14