八氢-喹啉嗪-3-羧酸乙酯 | 76211-05-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹嗪类
• 中文名称: 八氢-喹啉嗪-3-羧酸乙酯
• 英文名称: ethyl octahydro-2H-quinolizine-3-carboxylate
• 英文别名: 3-Carbethoxy-chinolizidin；octahydro-quinolizine-3-carboxylic acid ethyl ester；ethyl 2,3,4,6,7,8,9,9a-octahydro-1H-quinolizine-3-carboxylate
• CAS: 76211-05-7
• 化学式: C₁₂H₂₁NO₂
• 分子量: 211.304
• InChiKey: ICWZXKPBSHGFEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2915900090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  八氢-喹啉嗪-3-羧酸乙酯 在 lithium aluminium tetrahydride 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.25h， 生成 N-(3,4-dichloro-2-fluorophenyl)-6-(methyloxy)-7-[(octahydro-2H-quinolizin-3-ylmethyl)oxy]quinazolin-4-amine
  参考文献：
  名称：

  Receptor-Type Kinase Modulators and Methods of Use

  摘要：

  本发明提供了用于调节受体激酶活性的化合物，特别是ephrin和EGFR，并利用这些化合物及其药物组合物治疗由受体激酶活性介导的疾病的方法。由受体激酶活性介导的疾病包括但不限于部分表现为细胞增殖异常水平（即肿瘤生长）、程序性细胞死亡（凋亡）、细胞迁移和侵袭以及与肿瘤生长相关的血管生成的疾病。本发明的化合物包括“谱选择性”激酶调节剂，这些化合物抑制、调节和/或调节跨受体型酪氨酸激酶亚家族的信号传导，包括ephrin和EGFR。

  公开号：

  US20160129032A1
• 作为产物：
  描述：

  1-Azabicyclo[4.4.0]decane-3-carbonitrile 、 盐酸 、 乙醇 以81%的产率得到
  参考文献：
  名称：

  KOSHINAKA E.; OGAWA N.; KURATA S.; YAMAGASHI K.; KUBO S.; MATSUBARA I.; K+, CHEM. AND PHARM. BULL., 1979, 27, NO 6, 1454-1463

  摘要：

  DOI：

文献信息

• Studies on antispasmodics. I. Synthesis and anticholinergic activity of 1-, 2-, and 3-diarylmethylenequinolizidine quaternary ammonium salts.
  作者：EIICHI KOSHINAKA、NOBUO OGAWA、SAKAE KURATA、KAGARI YAMAGISHI、SHINJI KUBO、ISSEI MATSUBARA、HIDEO KATO

  DOI：10.1248/cpb.27.1454

  日期：——

  As part of a search for new antispasmodic agents, we have synthesized 1-, 2-, and 3-diarylmethylenequinolizidine quaternary ammonium salts (4-15), which can be regarded as conformationally rigid derivatives of diphemanil methylsulfate (1) or timepidium bromide (2). The Grignard reaction of ethoxycarbonylquinolizidines (16, 21, and 30) with phenyllithium or 2-thienylmagnesiumbromide, followed by dehydration, afforded diarylmethylenequinolizidines (19, 20, 24, 25, 33, and 34). Quaternization of the 1-substituted derivatives (19 and 20) with methyl bromide afforded only the cis methobromides (4 and 6). On similar treatment, the 2-substituted derivatives (24 and 25) each afforded two isomeric methobromides, the trans (8a and 9a) and cis (8b and 9b), and the 3-substituted derivatives also afforded trans (12a and 13a) and cis methobromides (12b and 13b). The stereochemistry of these methobromides was confirmed by thermal isomerization experiments and the chemical shifts of N+-methyl signals in the 1H-and 13C-nuclear magnetic resonance spectra. The quaternary ammonium salts (4-15) exhibited more potent anticholinergic activity than 1 and 2, and the activities of several compounds (8, 9, and 13) were equal to or greater than that of atropine. The structure-activity relationships of these compounds are discussed.

  作为寻找新型解痉药物的一部分，我们合成了1-、2-和3-二芳基亚甲基吡咯并吡啶季铵盐（4-15），它们可以被认为是二苯胺甲基硫酸酯（1）或替匹碘胺溴化物（2）的构象刚性衍生物。将乙氧羰基吡咯并吡啶（16、21和30）与苯基锂或2-噻吩基溴化镁进行格氏反应，随后进行脱水，得到了二芳基亚甲基吡咯并吡啶（19、20、24、25、33和34）。用甲基溴对1-取代衍生物（19和20）进行季铵化，仅得到了顺式甲溴化物（4和6）。类似的处理下，2-取代衍生物（24和25）分别得到了反式（8a和9a）和顺式（8b和9b）两种异构的甲溴化物，3-取代衍生物也得到了反式（12a和13a）和顺式甲溴化物（12b和13b）。这些甲溴化物的立体化学通过热异构化实验和1H及13C核磁共振谱中N+-甲基信号的化学位移得到确认。季铵盐（4-15）表现出比1和2更强的抗胆碱能活性，其中几种化合物（8、9和13）的活性等于或高于阿托品。本文讨论了这些化合物的结构-活性关系。
• [EN] RECEPTOR-TYPE KINASE MODULATORS AND METHODS OF USE<br/>[FR] MODULATEURS DE KINASE DE TYPE RECEPTEUR ET PROCEDES D'UTILISATION
  申请人：EXELIXIS INC

  公开号：WO2004006846A2

  公开（公告）日：2004-01-22

  The present invention provides compounds for modulating receptor kinase activity, particularly ephrin and EGFR, and methods of treating diseases mediated by receptor kinase activity utilizing the compounds and pharmaceutical compositions thereof. Diseases mediated by receptor kinase activity include, but are not limited to, diseases characterized in part by abnormal levels of cell proliferation (i.e. tumor growth), programmed cell death ( apoptosis), cell migration and invasion and angiogenesis associated with tumor growth. Compounds of the invention include 'spectrum selective' kinase modulators, compounds that inhibit, regulate and/or mo dulate signal transduction across subfamilies of receptor-type tyrosine kinases, including ephrin and EGFR.

  本发明提供了用于调节受体激酶活性的化合物，特别是调节ephrin和EGFR，以及利用这些化合物和其制剂治疗受受体激酶活性介导的疾病的方法。受受体激酶活性介导的疾病包括但不限于部分由细胞增殖异常水平（即肿瘤生长）、程序性细胞死亡（凋亡）、细胞迁移和侵袭以及与肿瘤生长相关的血管生成所特征化的疾病。本发明的化合物包括“光谱选择性”激酶调节剂，这些化合物抑制、调节和/或调节受体型酪氨酸激酶亚家族之间的信号转导，包括ephrin和EGFR。
• Receptor-type kinase modulators and methods of use
  申请人：Rice D Kenneth

  公开号：US20060069077A1

  公开（公告）日：2006-03-30

  The present invention provides compounds for modulating receptor kinase activity, particularly ephrin and EGFR, and methods of treating diseases mediated by receptor kinase activity utilizing the compounds and pharmaceutical compositions thereof. Diseases mediated by receptor kinase activity include, but are not limited to, diseases characterized in part by abnormal levels of cell proliferation (i.e. tumor growth), programmed cell death (apoptosis), cell migration and invasion and angiogenesis associated with tumor growth. Compounds of the invention include “spectrum selective” kinase modulators, compounds that inhibit, regulate and/or modulate signal transduction across subfamilies of receptor-type tyrosine kinases, including ephrin and EGFR.

  本发明提供了用于调节受体激酶活性的化合物，特别是调节ephrin和EGFR等受体激酶活性的化合物，并利用这些化合物和其制剂治疗由受体激酶活性介导的疾病的方法。由受体激酶活性介导的疾病包括但不限于部分表现为细胞增殖异常水平（即肿瘤生长）、程序性细胞死亡（凋亡）、细胞迁移和侵袭以及与肿瘤生长相关的血管生成的疾病。本发明的化合物包括“光谱选择性”激酶调节剂，可以抑制、调节和/或调节受体型酪氨酸激酶亚家族之间的信号转导，包括ephrin和EGFR。
• c-MET MODULATORS AND METHOD OF USE
  申请人：BANNEN CANNE LYNNE

  公开号：US20070244116A1

  公开（公告）日：2007-10-18

  The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. More specifically, the invention provides quinazolines and quinolines which inhibit, regulate, and/or modulate kinase receptor, particularly c-Met, KDF, c-Kit, flt-3 and flt-4, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds.

  本发明提供了用于调节蛋白激酶酶活性，以调节细胞活动，如增殖、分化、程序性细胞死亡、迁移和化学侵袭的化合物。更具体地，本发明提供了喹唑啉和喹啉，这些化合物抑制、调节和/或调节激酶受体，特别是c-Met、KDF、c-Kit、flt-3和flt-4，与上述细胞活动变化相关的信号转导途径，包含这些化合物的组合物，以及使用它们治疗激酶依赖性疾病和病况的方法。本发明还提供制备上述化合物的方法和包含这些化合物的组合物。
• C-MET MODULATORS AND METHOD OF USE
  申请人：Bannen Canne Lynne

  公开号：US20070225307A1

  公开（公告）日：2007-09-27

  The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. More specifically, the invention provides quinazolines and quinolines which inhibit, regulate, and/or modulate kinase receptor, particularly c-Met, KDF, c-Kit, flt-3 and flt-4, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds.

  本发明提供了用于调节蛋白激酶酶活性以调节细胞活动（如增殖、分化、程序性细胞死亡、迁移和化学入侵）的化合物。更具体地，该发明提供了喹唑啉和喹啉，它们能够抑制、调节和/或调节激酶受体，特别是c-Met、KDF、c-Kit、flt-3和flt-4，与上述细胞活动变化相关的信号转导途径，包含这些化合物的组合物，以及使用它们治疗激酶依赖性疾病和病况的方法。本发明还提供了制备上述化合物和包含这些化合物的组合物的方法。