2,3-二氢-5-氨基-1,4-苯并二噁英盐酸盐 | 16081-46-2

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 中文名称: 2,3-二氢-5-氨基-1,4-苯并二噁英盐酸盐
• 中文别名: 2,3-二氢-1,4-苯并二噁英-5-胺盐酸盐；2,3-二氢-5-氨基-1,4-苯并二恶英盐酸盐
• 英文名称: 2,3-dihydro-1,4-benzodioxin-5-amine hydrochloride
• 英文别名: 2,3-dihydro-1,4-benzodioxin-5-amine;hydrochloride
• CAS: 16081-46-2
• 化学式: C₈H₉NO₂*ClH
• mdl: MFCD08056380
• 分子量: 187.626
• InChiKey: WBCBWPNJOUYRGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.66
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  44.5
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  4-chloro-7-(2-pyrrolidin-1-ylethoxy)-5-(tetrahydro-2H-pyran-4-yloxy)quinazoline 、 2,3-二氢-5-氨基-1,4-苯并二噁英盐酸盐 以 异丙醇 为溶剂， 反应 1.5h， 以60%的产率得到N-(2,3-dihydro-1,4-benzodioxin-5-yl)-7-(2-pyrrolidin-1-ylethoxy)-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine
  参考文献：
  名称：

  N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a Novel, Highly Selective, Orally Available, Dual-Specific c-Src/Abl Kinase Inhibitor

  摘要：

  Src family kinases (SFKs) are nonreceptor tyrosine kinases that are reported to be critical for cancer progression. We report here a novel subseries of C-5-substituted anilinoquinazolines that display high affinity and specificity for the tyrosine kinase domain of the c-Src and Abl enzymes. These compounds exhibit high selectivity for SFKs over a panel of recombinant protein kinases, excellent pharmacokinetics, and in vivo activity following oral dosing. N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine (AZD0530) inhibits c-Src and Abl enzymes at low nanomolar concentrations and is highly selective over a range of kinases. AZD0530 displays excellent pharmacokinetic parameters in animal preclinically and in man (t(1/2) = 40 h). AZD0530 is a potent inhibitor of tumor growth in a c-Src-transfected 3T3-fibroblast xenograft model in vivo and led to a significant increase in survival in a highly aggressive, orthotopic model of human pancreatic cancer when dosed orally once daily. AZD0530 is currently undergoing clinical evaluation in man.

  DOI：

  10.1021/jm060434q
• 作为产物：
  描述：

  2,3-二氢-1,4-苯并二烷-5-羧酸 在 sodium hydroxide 、 PPA 、 盐酸羟胺 作用下， 以 乙酸乙酯 为溶剂， 生成 2,3-二氢-5-氨基-1,4-苯并二噁英盐酸盐
  参考文献：
  名称：

  Piperazine derivatives as therapeutic agents

  摘要：

  公式I的替代哌嗪化合物##STR1##，其中HET是替代的吡唑啉、咪唑或1,2,4-三唑，在治疗中枢神经系统疾病方面具有实用性，例如抑郁症、焦虑症、精神病（例如精神分裂症）、迟发性运动障碍、帕金森病、肥胖症、高血压、图雷特综合征、性功能障碍、药物成瘾、药物滥用、认知障碍、阿尔茨海默病、老年性痴呆、强迫行为、恐慌发作、社交恐惧症、进食障碍和厌食症、心血管和脑血管疾病、非胰岛素依赖型糖尿病、高血糖症、便秘、心律失常、神经内分泌系统疾病、压力、前列腺肥大和痉挛症。

  公开号：

  US06114334A1

文献信息

• Quinoline derivatives as phosphodiesterase inhibitors
  申请人：Barker David Michael

  公开号：US20060178416A1

  公开（公告）日：2006-08-10

  There are provided according to the invention novel compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R19, R20, and R34 are as described in the specification, processes for preparing them, formulations containing them and their use in therapy for the treatment of inflammatory diseases.

  根据本发明提供了公式(I)的新化合物或其药学上可接受的盐，其中R1、R2、R19、R20和R34如规范所述，以及制备它们的过程、包含它们的制剂和它们在治疗炎症性疾病方面的用途。
• Quinoline Derivatives As Phosphodiesterase Inhibitors
  申请人：Baldwin Ian Robert

  公开号：US20090312325A1

  公开（公告）日：2009-12-17

  There are provided according to the invention novel compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R19, R20, and R34 are as described in the specification, processes for preparing them, formulations containing them and their use in therapy for the treatment of inflammatory diseases.

  根据本发明提供了一种新的化合物式(I)或其药学上可接受的盐，其中R1、R2、R19、R20和R34如规范所述，以及制备它们的过程、含有它们的制剂以及它们在治疗炎症性疾病方面的用途。
• Quinoline derivatives as phosphodiesterase inhibitors
  申请人：GLAXO GROUP LIMITED

  公开号：EP1944305A1

  公开（公告）日：2008-07-16

  There are provided according to the invention novel compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R19, R20 and R34 are as described in the specification, processes for preparing them, formulations containing them and their use in therapy for the treatment of inflammatory diseases.

  根据本发明提供了式 (I) 的新型化合物或其药学上可接受的盐类（其中 R1、R2、R19、R20 和 R34 如说明书所述）、制备它们的工艺、含有它们的制剂以及它们在治疗炎症性疾病中的用途。
• Discovery of a New Class of Anilinoquinazoline Inhibitors with High Affinity and Specificity for the Tyrosine Kinase Domain of c-Src
  作者：Patrick A. Plé、Tim P. Green、Laurent F. Hennequin、Jon Curwen、Michael Fennell、Jack Allen、Christine Lambert-van der Brempt、Gerard Costello

  DOI：10.1021/jm030317k

  日期：2004.2.1

  Deregulated activity of the nonreceptor tyrosine kinase c-Src is believed to result in signal transduction, cytoskeletal and adhesion changes, ultimately promoting a tumor-invasive phenotype. We report here the discovery of a new class of anilinoquinazoline inhibitors with high affinity and specificity for the tyrosine kinase domain of the c-Src enzyme. Special attention was directed toward finding inhibitors selective against KDR tyrosine kinase in order to ensure that the in vivo profile of a specific Src inhibitor could be determined. The 4-aminobenzodioxole quinazoline series gave compounds with excellent potency and selectivity. The most interesting compounds were evaluated in vivo and displayed good pharmacokinetics following oral dosing. Compounds such as the aminobenzodioxoles were shown to be potent inhibitors of tumor growth in a c-Src-transformed 3T3 xenograft model in vivo, resulting in more than 90% growth inhibition at doses as low as 6 mg/kg po once daily. Src tyrosine kinase inhibitors such as these may provide a novel therapeutic modality for targeting cancer invasion and metastasis.
• PIPERAZINE DERIVATIVES AS THERAPEUTIC AGENTS
  申请人：Knoll GmbH

  公开号：EP0839144B1

  公开（公告）日：2001-09-19