8-Methoxy-7-[2-(4-methyl-1-piperazinyl)ethoxy]-4-(3,4,5-trimethoxyanilino)benzo[g]quinoline-3-carbonitrile

• 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: 8-Methoxy-7-[2-(4-methyl-1-piperazinyl)ethoxy]-4-(3,4,5-trimethoxyanilino)benzo[g]quinoline-3-carbonitrile
• 英文别名: 8-Methoxy-7-[2-(4-methylpiperazin-1-yl)ethoxy]-4-[(3,4,5-trimethoxyphenyl)amino]benzo[g]quinoline-3-carbonitrile；8-methoxy-7-[2-(4-methylpiperazin-1-yl)ethoxy]-4-(3,4,5-trimethoxyanilino)benzo[g]quinoline-3-carbonitrile
• 化学式: C₃₁H₃₅N₅O₅
• 分子量: 557.649
• InChiKey: KSXHQBAKUGXZSD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-(2-chloroethoxy)-5-methoxyphthalaldehyde 、 3-硝基丙酸乙酯 、 N,N-二甲基甲酰胺二甲基缩醛 、 3,4,5-三甲氧基苯胺 、 乙腈 、 alkaline earth salt of/the/ methylsulfuric acid 以142 mg的产率得到8-Methoxy-7-[2-(4-methyl-1-piperazinyl)ethoxy]-4-(3,4,5-trimethoxyanilino)benzo[g]quinoline-3-carbonitrile
  参考文献：
  名称：

  4-Anilino-7,8-dialkoxybenzo[g]quinoline-3-carbonitriles as Potent Src Kinase Inhibitors

  摘要：

  It has been previously reported that appropriately substituted 4-anilinoquinoline-3-carbonitriles are potent inhibitors of Src kinase, with biological activity in vitro and in vivo. Structural modifications to these compounds have been explored, providing the 4-anilinobenzo[g] quinoline-3-carbonitriles as a series with enhanced Src inhibitory properties. The synthesis and structure-activity relationships of these 4-anilino-7,8-dialkoxybenzo[g]quinoline-3-carbonitriles are presented here. Analogues with cyclic basic amine groups attached via ethoxy linkages at the C-8 position were the most active in vitro, with subnanomolar IC50 values against Src kinase observed for a majority of the compounds synthesized. Compound 17d was more potent in vitro than the analogously substituted 4-anilinoquinoline-3-carbonitrile SKI-606, which is undergoing evaluation in clinical trials. The most potent analogue synthesized was 17a, with an IC50 of 0.15 nM against Src kinase and with an IC50 of 10 nM against Src-transformed fibroblasts. Molecular modeling studies provided a rationale for the exceptional activity observed for these compounds, with favorable van der Waals interactions playing the major role. Compound 17c was found to be highly selective for Src kinase when tested against a panel of other kinases, with modest selectivity versus the Src family kinases Lyn and Fyn. Following ip dosing at 50 mg/kg, analogues 17c and 17d were shown to have plasma levels that significantly exceeded the cellular IC50 values against Src-transformed fibroblasts. In an Src-transformed fibroblast xenograft model, both compounds exhibited a significant inhibition of tumor growth.

  DOI：

  10.1021/jm050512u

文献信息

• Tricyclic protein kinase inhibitors
  申请人：American Home Products Corporation

  公开号：US20010051620A1

  公开（公告）日：2001-12-13

  This invention provides compounds of formula 1, having the structure 1 which are useful as inhibitors of protein tyro sine kinase and are antiproliferative agents.

  这项发明提供了具有结构1的化合物，这些化合物可作为蛋白酪氨酸激酶的抑制剂，是抗增殖剂。
• [EN] 6-ALKENYL-, 6-ALKINYL- AND 6-EPOXY-EPOTHILONE DERIVATIVES, PROCESS FOR THEIR PRODUCTION, AND THEIR USE IN PHARMACEUTICAL PREPARATIONS<br/>[FR] DERIVES 6-ALCENYL-, 6-ALKINYL-, ET 6-EPOXY-EPOTHILONE, PROCEDE DE PREPARATION ET LEUR UTILISATION DANS DES PREPARATIONS PHARMACEUTIQUES
  申请人：SCHERING AG

  公开号：WO2000066589A1

  公开（公告）日：2000-11-09

  This invention describes the new 6-alkenyl- and 6-alkinyl- epothilone derivatives of general formula (I) in which R?1a, R1b, R2a, R3a, R3b, R4, R5, R6, R7¿, A, Y, D, E, G, Y and Z have the meanings that are indicated in the description. The new compounds interact with tubulin by stabilizing microtubuli that are formed. They are able to influence the cell-splitting in a phase-specific manner and thus find use in treating diseases or conditions associated with the need for cell growth, division and/or proliferation. Thus the compounds are suitable for treating malignant tumors, for example, ovarian, stomach, colon, adeno-, breast, lung, head and neck carcinomas, malignant melanoma, acute lymphocytic and myelocytic leukemia. In addition, they are suitable for anti-angiogenesis therapy as well as for treatment of chronic inflammatory diseases (such as psoriasis, arthritis). Methods of use and preparation of the compounds are also described.

  本发明描述了一种新的6-烯基和6-炔基-环毒素衍生物，其通式为(I)，其中R1a、R1b、R2a、R3a、R3b、R4、R5、R6、R7、A、Y、D、E、G、Y和Z的含义如说明书中所示。新化合物通过稳定形成的微管蛋白来与微管蛋白相互作用。它们能够以特定的方式影响细胞分裂，因此可用于治疗与细胞生长、分裂和/或增殖有关的疾病或症状。因此，这些化合物适用于治疗恶性肿瘤，例如卵巢、胃、结肠、腺癌、乳腺、肺、头颈癌、恶性黑色素瘤、急性淋巴细胞性和髓性白血病。此外，它们还适用于抗血管生成治疗以及治疗慢性炎症性疾病（如牛皮癣、关节炎）。还描述了这些化合物的使用和制备方法。
• [EN] TRICYCLIC PROTEIN KINASE INHIBITORS<br/>[FR] INHIBITEURS TRICYCLIQUES DE PROTEINE KINASE
  申请人：AMERICAN HOME PROD

  公开号：WO2001047892A1

  公开（公告）日：2001-07-05

  This invention provides compounds of formula (1) which are useful as inhibitors of protein tyrosine kinase and are antiproliferative agents.

  本发明提供了一种式子为(1)的化合物，它们可用作蛋白酪氨酸激酶的抑制剂并具有抗增殖作用。
• 6-ALKENYL-, 6-ALKINYL- AND 6-EPOXY-EPOTHILONE DERIVATIVES, PROCESS FOR THEIR PRODUCTION, AND THEIR USE IN PHARMACEUTICAL PREPARATIONS
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：EP1173441A1

  公开（公告）日：2002-01-23
• TRICYCLIC PROTEIN KINASE INHIBITORS
  申请人：Wyeth

  公开号：EP1242382A1

  公开（公告）日：2002-09-25