7-(benzyloxy)-4-chloro-6-methoxycinnoline | 398127-72-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 7-(benzyloxy)-4-chloro-6-methoxycinnoline
• 英文别名: 6-methoxy-7-benzyloxy-4-chlorocinnoline；7-Benzyloxy-4-chloro-6-methoxy cinnoline；4-chloro-6-methoxy-7-phenylmethoxycinnoline
• CAS: 398127-72-5
• 化学式: C₁₆H₁₃ClN₂O₂
• 分子量: 300.744
• InChiKey: ZBJBIUWSPOXZDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-(benzyloxy)-4-chloro-6-methoxycinnoline 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 48.0h， 生成 4-chloro-6-methoxycinnolin-7-ol
  参考文献：
  名称：

  Synthesis and in vitro characterization of cinnoline and benzimidazole analogues as phosphodiesterase 10A inhibitors

  摘要：

  Fifteen cinnoline analogues and six benzimidazole phosphodiesterase 10A (PDE10A) inhibitors were synthesized as potential PET radiopharmaceuticals and their in vitro activity as PDE10A inhibitors was determined. Nine out of twenty-one compounds were potent inhibitors of PDE10A with IC50 values ranging from 1.5 to 18.6 nM. Notably, the IC50 values of compounds 26a, 26b, and 33c were 1.52 +/- 0.18, 2.86 +/- 0.10, and 3.73 +/- 0.60 nM, respectively; these three compounds also showed high in vitro selectivity (> 1000-fold) for PDE10A over PDE 3A/3B, PDE4A/4B. The high potency and selectivity of these three compounds suggests that they could be radiolabeled with PET radionuclides for further evaluation of their in vivo pharmacological behavior and ability to quantify PDE10A in the brain. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.054
• 作为产物：
  描述：

  1-(4-(苄氧基)-5-甲氧基-2-硝基苯基)乙酮 在 盐酸 、 铁粉 、 溶剂黄146 、 三氯氧磷 作用下， 以 乙醇 、 水 为溶剂， 反应 22.25h， 生成 7-(benzyloxy)-4-chloro-6-methoxycinnoline
  参考文献：
  名称：

  一种杂环类化合物、制备方法及应用

  摘要：

  本申请涉及医药技术领域中的一种杂环类化合物，该类化合物为结构通式Ⅰ或其药学上可接受的盐，其中R1、R2、R3、R4、R5、R6、X、Y、Z、Cy1、Cy2、m、n及t具有在说明书中给出的含义，此外，本发明还公开了该类化合物及其药学上可接受的盐在制备治疗由于酪氨酸激酶异常高表达所引起疾病的药物中的用途，特别是在制备治疗和预防癌症的药物中的用途。

  公开号：

  CN111253385A

文献信息

• Cinnoline compounds
  申请人：——

  公开号：US20030212055A1

  公开（公告）日：2003-11-13

  The invention relatest to compounds of the formula (I) wherein either any one of G 1 , G 2 , G 3 , G 4 and G 5 is nitrogen and the other four are —CH—, or G 1 , G 2 , G 3 , G 4 and G 5 are all —CH—; Z is —O—, —NH—, —S—, —CH 2 — or a direct bond; Z is linked to any one of G 1 , G 2 , G 3 and G 4 which is a free carbon atom; n is an integer from 0 to 5; any of the substitutents R 1 may be attached at any free carbon atom of the indole, azaindole or indazole group; m is an integer from 0 to 3; R a represents hydrogen; R b represents hydrogen or another value as defined herein; R 1 represents hydrogen, oxo, hydroxy, halogeno, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkoxy, C 1-4 -alkyl, aminoC 1-4 alkyl, C 1-3 alkylaminoC 1-4 alkyl, di(C 1-3 alkyl)aminoC 1-4 alkyl, —C 1-5 alkyl(ring B) wherein ring B is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, N-methylpiperazinly, N-ethylpiperazinyl, morpholino and thiomorpholino; R 2 represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 aklylsulphanyl, —NR 3 R 4 (wherein R 3 and R 4 , which may be the same or different, each represents hydrogen or C 1-3 alkyl), or R 5 X 1 — (wherein R 5 and X 1 are as defined herein) and salts thereof, processes for the preparation of such compounds, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and the use of a compound of formula I in the manufacture of medicament for the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

  该发明涉及以下式(I)的化合物，其中G1、G2、G3、G4和G5中的任何一个是氮，其他四个是—CH—，或者G1、G2、G3、G4和G5都是—CH—；Z是—O—、—NH—、—S—、—CH2—或直接键；Z与G1、G2、G3和G4中的任何一个自由碳原子相连；n是从0到5的整数；R1的任何取代基可能连接到吲哚、氮杂吲哚或吲唑基团的任何自由碳原子；m是从0到3的整数；Ra代表氢；Rb代表氢或本文中定义的另一个值；R1代表氢、氧代、羟基、卤代、C1-4烷基、C1-4烷氧基、C1-4烷氧基、C1-4烷基、氨基C1-4烷基、C1-3烷基氨基C1-4烷基、二(C1-3烷基)氨基C1-4烷基、—C1-5烷基(环B)，其中环B选自氮杂环丙烷基、吡咯烷基、哌啶基、哌嗪基、N-甲基哌嗪基、N-乙基哌嗪基、吗啉和硫代吗啉；R2代表氢、羟基、卤代、氰基、硝基、三氟甲基、C1-3烷基、C1-3烷氧基、C1-3烷基硫基、—NR3R4(其中R3和R4，可能相同也可能不同，各自代表氢或C1-3烷基)，或R5X1—(其中R5和X1如本文所定义)及其盐，制备这类化合物的方法，含有式I的化合物或其药学上可接受的盐作为活性成分的药物组合物，以及利用式I的化合物制备药物，用于在温血动物中产生抗血管生成和/或血管通透性降低作用。式I的化合物及其药学上可接受的盐抑制VEGF的作用，这是治疗多种疾病状态的有价值特性，包括癌症和类风湿性关节炎。
• 一种杂环类化合物、制备方法及应用
  申请人：遵义医科大学珠海校区

  公开号：CN111253385A

  公开（公告）日：2020-06-09

  本申请涉及医药技术领域中的一种杂环类化合物，该类化合物为结构通式Ⅰ或其药学上可接受的盐，其中R1、R2、R3、R4、R5、R6、X、Y、Z、Cy1、Cy2、m、n及t具有在说明书中给出的含义，此外，本发明还公开了该类化合物及其药学上可接受的盐在制备治疗由于酪氨酸激酶异常高表达所引起疾病的药物中的用途，特别是在制备治疗和预防癌症的药物中的用途。
• CINNOLINE COMPOUNDS
  申请人：AstraZeneca AB

  公开号：EP1309587B1

  公开（公告）日：2008-12-31
• US6887874B2
  申请人：——

  公开号：US6887874B2

  公开（公告）日：2005-05-03
• [EN] CINNOLINE COMPOUNDS<br/>[FR] COMPOSES DE CINNOLINE
  申请人：ASTRAZENECA AB

  公开号：WO2002012228A1

  公开（公告）日：2002-02-14

  The invention relatest to compounds of the formula (I) wherein either any one of G1, G2, G3, G4 and G5 is nitrogen and the other four are -CH-, or G1, G2, G3, G4 and G5 are all -CH-; Z is -O-, -NH-, -S-, -CH2- or a direct bond; Z is linked to any one of G1, G2, G3 and G4 which is a free carbon atom; n is an integer from 0 to 5; any of the substitutents R1 may be attached at any free carbon atom of the indole, azaindole or indazole group; m is an integer from 0 to 3; Ra represents hydrogen; Rb represents hydrogen or another value as defined herien; R1 represents hydrogen, oxo, hydroxy, halogeno, C¿1-4?alkyl, C1-4alkoxy, C1-4alkoxyC1-4alkyl, aminoC1-4alkyl, C1-3alkylaminoC1-4alkyl, di(C1-3alkyl)aminoC1-4alkyl, -C1-5alkyl(ring B) wherein ring B is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, N-methylpiperazinly, N-ethylpiperazinyl, morpholino and thiomorpholino; R?2¿ represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C¿1-3?alkyl, C1-3alkoxy, C1-3aklylsulphanyl, -NR?3R4¿ (wherein R?3 and R4¿, which may be the same or different, each represents hydrogen or C¿1-3?alkyl), or R?5X1¿-(wherein R?5 and X1¿ are as defined herein) and salts thereof, processes for the preparation of such compounds, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and the use of a compound of formula I in the manufacture of medicament for the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals.The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.