lactam of o-(3-aminopyridyl-4)benzoic acid | 89052-51-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: lactam of o-(3-aminopyridyl-4)benzoic acid
• 英文别名: benzo[c][1,7]naphthyridin-6(5H)-one；2,10-Diazaphenanthren-9(10H)-one；5H-Benzo[c][1,7]naphthyridin-6-one
• CAS: 89052-51-7
• 化学式: C₁₂H₈N₂O
• 分子量: 196.208
• InChiKey: RGJWBNVVXDVAMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  silver nitrate 、 lactam of o-(3-aminopyridyl-4)benzoic acid 、 cis-diamminedichloroplatinum(II) 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以59%的产率得到cis-[Pt(NH₃)₂(3-aza-5H-phenanthridin-6-one)Cl]NO₃
  参考文献：
  名称：

  Platinated benzonaphthyridone is a stronger inhibitor of poly(ADP-ribose) polymerase-1 and a more potent anticancer agent than is the parent inhibitor

  摘要：

  Inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) have shown to be promising in clinical trials against cancer and other diseases, and lots of efforts have been put into the development of organic compounds as more potent PARP-1 inhibitors. Here we describe a strategy to conveniently obtain metal-based PARP-1 inhibitors with enhanced biological activities by conjugating platinum moiety with an original inhibitor, e.g., benzonaphthyridone. Based on the structure activity relationship analysis of PARP-1 inhibitors, three platinated PARP-1 inhibitors were designed, and the complexes were synthesized and characterized. Complex 3 presented significantly enhanced cytotoxicity against a panel of human cancer cells and a 10-fold increased inhibitory effect against recombinant PARP-1 compared with the original PARP-1 inhibitor. Complex 3 was as cytotoxic as cisplatin and its spectrum of anticancer activity was identical to that of cisplatin. The complex was able to enter into cancer cells efficiently, bind to DNA well, and block cell cycle at G(2)/M phase, indicating that complex 3 is an effective anticancer agent with a distinct mechanism of action. Our study implies that the conjugation of platinum with PARP-1 inhibitors could be a valid strategy to obtain more potent anticancer agents with improved biological activities. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.10.062
• 作为产物：
  描述：

  2-(二异丙基羰基)苯硼酸 在 盐酸 、 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 甲醇 、 乙二醇二甲醚 为溶剂， 反应 42.0h， 生成 lactam of o-(3-aminopyridyl-4)benzoic acid
  参考文献：
  名称：

  Design and Synthesis of Poly ADP-ribose Polymerase-1 Inhibitors. 2. Biological Evaluation of Aza-5[H]-phenanthridin-6-ones as Potent, Aqueous-Soluble Compounds for the Treatment of Ischemic Injuries

  摘要：

  A series of aza-5[H]-phenanthridin-6-ones were synthesized and evaluated as inhibitors of poly ADP-ribose polymerase-1 (PARP-1). Inhibitory potency of the unsubstituted aza-5[H]-phenanthridin-6-ones (i.e., benzonaphyhyridones) was dependent on the position of the nitrogen atom within the core structure. The A ring nitrogen analogues (7-, 8-, and 10-aza-5[H]-phenanthridin-6-ones) were an order of magnitude less potent than C ring nitrogen analogues (1-, 2-, 3-, and 4-aza-5[H]-phenanthridin-6-ones). Preliminary stroke results from 1- and 2-aza-5[H]-phenanthridin-6-one prompted structure-activity relationships to be established for several 2- and 3-substituted 1-aza-5[H]-phenanthridin-6-ones. The 2-substituted 1-aza-5[H]-phenanthridin-6-ones were designed to improve the solubility and pharmacokinetic profiles for this series of PARP-1 inhibitors. Most importantly, three compounds from this series demonstrated statistically significant protective effects in rat models of stroke and heart ischemia.

  DOI：

  10.1021/jm030109s

文献信息

• A Pd-catalyzed, boron ester-mediated, reductive cross-coupling of two aryl halides to synthesize tricyclic biaryls
  作者：Zhilong Chen、Xiaodong Wang

  DOI：10.1039/c7ob01237c

  日期：——

  Tricyclic biaryls are important scaffold structures in many natural products and lead compounds in drug discovery. The formation of a biaryl unit is often the key step for the synthesis of tricyclic biaryls. Despite significant progress toward the synthesis of biaryl compounds in recent years, the direct cross-coupling of two different aryl halides is still challenging and robust methods are lacking

  三环联芳基在许多天然产物中是重要的支架结构，在药物发现中是先导化合物。联芳基单元的形成通常是合成三环联芳基的关键步骤。尽管近年来在合成联芳基化合物方面取得了重大进展，但是两种不同的芳基卤化物的直接交叉偶联仍然具有挑战性，并且缺乏可靠的方法。在本文中，我们报道了在钯催化剂和硼酸酯存在下两种不同的芳基卤化物的直接交叉偶联，这为合成三环联芳基提供了一种新的有用的互补方法。
• Photoreaction of 2-Halo-<i>N</i>-pyridinylbenzamide:  Intramolecular Cyclization Mechanism of Phenyl Radical Assisted with n-Complexation of Chlorine Radical
  作者：Yong-Tae Park、Chang-Hee Jung、Moon-Sub Kim、Kwang-Wook Kim、Nam Woong Song、Dongho Kim

  DOI：10.1021/jo001470e

  日期：2001.4.1

  3a, and 4 afforded photocyclized products, benzo[c]naphthyridinones (6-9 and 16), in high yield, whereas the bromo analogues 1b, 2b, and 3b produced extensively photoreduced products, N-pyridinylbenzamides (1c, 10, and 11), with minor photocyclized product. Since the photocyclization reaction of 2-chloro-N-pyridinylbenzamide is retarded by the presence of oxygen and sensitized by the presence of a

  研究了2-卤代-N-吡啶基苯甲酰胺（图1中的1-4）的光化学行为。2-氯-N-吡啶基苯甲酰胺1a，2a，3a和4的光反应可提供高收率的光环化产物苯并[c]萘啶酮（6-9和16），而溴代类似物1b，2b和3b产生大量光还原的产品，N-吡啶基苯甲酰胺（1c，10和11），以及次要的光环化产品。由于2-氯-N-吡啶基苯甲酰胺的光环化反应由于氧气的存在而被阻滞，并且由于三重态敏化剂，丙酮或苯乙酮的存在而被敏化，因此氯类似物的三重态处于反应中。由于在2-氯-N-吡啶基苯甲酰胺的激光闪光光解中发现了几种自由基中间体，尤其是氯自由基的n-络合物，提出了苯基自由基与氯自由基的n-络合辅助的分子内环化机理，以用于环化反应：由1a激发而形成的氯代类似物（1a）的三重态（78 kcal / mol）经历均相裂解C-Cl键以产生苯基和氯基；当氯自由基通过n络合物保持相邻的吡啶基环时，苯基与吡啶基环的分子内芳基化反应产生共轭的2
• Platinated benzonaphthyridone is a stronger inhibitor of poly(ADP-ribose) polymerase-1 and a more potent anticancer agent than is the parent inhibitor
  作者：Beilei Wang、Hui Qian、Shek-Man Yiu、Jianwei Sun、Guangyu Zhu

  DOI：10.1016/j.ejmech.2013.10.062

  日期：2014.1

  Inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) have shown to be promising in clinical trials against cancer and other diseases, and lots of efforts have been put into the development of organic compounds as more potent PARP-1 inhibitors. Here we describe a strategy to conveniently obtain metal-based PARP-1 inhibitors with enhanced biological activities by conjugating platinum moiety with an original inhibitor, e.g., benzonaphthyridone. Based on the structure activity relationship analysis of PARP-1 inhibitors, three platinated PARP-1 inhibitors were designed, and the complexes were synthesized and characterized. Complex 3 presented significantly enhanced cytotoxicity against a panel of human cancer cells and a 10-fold increased inhibitory effect against recombinant PARP-1 compared with the original PARP-1 inhibitor. Complex 3 was as cytotoxic as cisplatin and its spectrum of anticancer activity was identical to that of cisplatin. The complex was able to enter into cancer cells efficiently, bind to DNA well, and block cell cycle at G(2)/M phase, indicating that complex 3 is an effective anticancer agent with a distinct mechanism of action. Our study implies that the conjugation of platinum with PARP-1 inhibitors could be a valid strategy to obtain more potent anticancer agents with improved biological activities. (C) 2013 Elsevier Masson SAS. All rights reserved.
• First metalation of aryl iodides: directed ortho-lithiation of iodopyridines, halogen-dance, and application to synthesis
  作者：P. Rocca、C. Cochennec、F. Marsais、L. Thomas-dit-Dumont、M. Mallet、A. Godard、G. Queguiner

  DOI：10.1021/jo00079a031

  日期：1993.12

  Metalation of iodopyridines was successfully achieved by LDA at low temperature. In many cases, lithiation is ortho directed by the iodo group which subsequently ortho-migrates very fast to give stabilized iodolithiopyridines. This procedure was applied to 2-fluoro-and 2-chloro-3-iodopyridines, 3-fluoro-4-iodopyridine, and 2-chloro-3-fluoro-4-iodopyridine. The resulting lithio intermediates were obtained in high yields before being reacted with electrophiles leading to various polysubstituted pyridines. Some of these iodopyridines were used as key molecules for the synthesis of fused polyaromatic alkaloids. Thus, perlolidine, delta-carbolines, and 2,10-diazaphenanthrenes were readily prepared in few steps taking advantage of the iodo reactivity for heteroring cross-coupling.
• PROSTAKOV, N. S.;VARLAMOV, A. V.;KLOCHKOV, A. M.;FOMICHEV, A. A., XIMIYA GETEROTSIKL. SOEDIN., 1983, N 12, 1669-1671
  作者：PROSTAKOV, N. S.、VARLAMOV, A. V.、KLOCHKOV, A. M.、FOMICHEV, A. A.

  DOI：——

  日期：——