6-chloro-2,3-dihydrobenzo[b][1,4]dioxin-5-amine | 164075-44-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 6-chloro-2,3-dihydrobenzo[b][1,4]dioxin-5-amine
• 英文别名: 6-chloro-2,3-dihydro-benzo[1,4]dioxin-5-ylamine；6-Chlor-2,3-dihydro-benzo[1,4]dioxin-5-ylamin；6-Chloro-2,3-dihydro-1,4-benzodioxin-5-amine
• CAS: 164075-44-9
• 化学式: C₈H₈ClNO₂
• 分子量: 185.61
• InChiKey: GHHFSINZUDUODS-UHFFFAOYSA-N

物化性质

• 沸点：
  295.1±40.0 °C(Predicted)
• 密度：
  1.399±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 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：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-chloro-2,3-dihydrobenzo[b][1,4]dioxin-5-amine 在 sodium hydroxide 作用下， 以 四氢呋喃 、 邻二氯苯 为溶剂， 反应 120.0h， 生成 t-butyl 4-(6-chloro-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  [EN] MULTIPLE D2 A(NTA)GONISTS/H3 ANTAGONISTS FOR TREATMENT OF CNS-RELATED DISORDERS
  [FR] MULTIPLES A(NTA)GONISTES DE D2/ANTAGONISTES DE H3 POUR LE TRAITEMENT DE TROUBLES ASSOCIÉS AU SNC

  摘要：

  本发明涉及按照式（III）的化合物；以及其药学上可接受的盐、水合物和溶剂合物。这些化合物具有D2受体拮抗/(部分)激动剂效应和H3拮抗效应，以及其药物组合物，以及将其用于预防或治疗中枢神经系统疾病的方法。

  公开号：

  WO2015069110A1
• 作为产物：
  描述：

  5-氨基-1,4-苯并二恶烷 在 N-氯代丁二酰亚胺 作用下， 以 氯仿 为溶剂， 以39%的产率得到6-chloro-2,3-dihydrobenzo[b][1,4]dioxin-5-amine
  参考文献：
  名称：

  [EN] MULTIPLE D2 A(NTA)GONISTS/H3 ANTAGONISTS FOR TREATMENT OF CNS-RELATED DISORDERS
  [FR] MULTIPLES A(NTA)GONISTES DE D2/ANTAGONISTES DE H3 POUR LE TRAITEMENT DE TROUBLES ASSOCIÉS AU SNC

  摘要：

  本发明涉及按照式（III）的化合物；以及其药学上可接受的盐、水合物和溶剂合物。这些化合物具有D2受体拮抗/(部分)激动剂效应和H3拮抗效应，以及其药物组合物，以及将其用于预防或治疗中枢神经系统疾病的方法。

  公开号：

  WO2015069110A1

文献信息

• N4-Unsubstituted N1-Arylpiperazines as High-Affinity 5-HT1A Receptor Ligands
  作者：Wilma Kuipers、Ineke van Wijngaarden、Chris G. Kruse、Marian ter Horst van Amstel、Martin Th. M. Tulp、Adriaan P. IJzerman

  DOI：10.1021/jm00011a014

  日期：1995.5

  found 2-methoxy substitution to be favorable, while 4-methoxy substitution was detrimental for 5-HT1A affinity. Substitution with annelated rings at the 2,3-positions was highly favorable for all investigated compounds, with the exception of a pyrrole ring. All other substitutions, except fluoro, in this class of heterobicyclic phenylpiperazines decreased affinity in the order: ortho > para > meta.

  为了探索对高5-HT1A亲和力的结构要求，合成了一系列芳基取代的N1-苯基哌嗪并评估了其从大鼠额叶皮层特定结合位点置换[3H] -8-OH-DPAT的能力。匀浆。我们发现2-甲氧基取代是有利的，而4-甲氧基取代对5-HT1A亲和力是有害的。除吡咯环外，对于所有研究的化合物，在2，3-位上用退火环取代非常有利。此类杂双环苯基哌嗪类中的所有其他取代基（氟基除外）按以下顺序降低亲和力：邻位>对位>间位。邻位和对位失去亲和力可能是由于空间因素：取代基或者与受体引起空间位阻，或者阻止化合物采用适当的构象与5-HT1A受体结合。构象分析与结构亲和性关系（SAR）结合表明，我们的芳基哌嗪可能以几乎共面的构象结合在5-HT1A受体上。在我们的5-HT1A受体模型中观察到的化合物的相互作用似乎与SAR数据一致。芳基哌嗪部分的芳族部分分别与螺旋IV和VI中的芳族残基Trp161和Phe362具有pi-pi相互
• [EN] OGA INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS D'OGA
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2019243535A1

  公开（公告）日：2019-12-26

  The present invention relates to O-GIcNAc hydrolase (OGA) inhibitors of formula (I). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C90RF72 mutations.

  本发明涉及式(I)的O-GIcNAc水解酶（OGA）抑制剂。该发明还涉及包含这种化合物的药物组合物，用于制备这种化合物和组合物的方法，以及利用这种化合物和组合物预防和治疗OGA抑制对其有益的疾病的应用，特别是τ蛋白病，如阿尔茨海默病或进行性核上性麻痹症；以及伴有τ病理的神经退行性疾病，特别是由C90RF72突变引起的肌萎缩侧索硬化和颞叶前叶痴呆症。
• <i>N</i>-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2<i>H</i>-pyran-4-yloxy)quinazolin-4-amine, a Novel, Highly Selective, Orally Available, Dual-Specific c-Src/Abl Kinase Inhibitor
  作者：Laurent F. Hennequin、Jack Allen、Jason Breed、Jon Curwen、Michael Fennell、Tim P. Green、Christine Lambert-van der Brempt、Rémy Morgentin、Richard A. Norman、Annie Olivier、Ludovic Otterbein、Patrick A. Plé、Nicolas Warin、Gerard Costello

  DOI：10.1021/jm060434q

  日期：2006.11.1

  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.
• Heertjes et al., Journal of the Chemical Society, 1955, p. 1313,1315
  作者：Heertjes et al.

  DOI：——

  日期：——
• OGA INHIBITOR COMPOUNDS
  申请人：Janssen Pharmaceutica NV

  公开号：US20210130352A1

  公开（公告）日：2021-05-06

  The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C9ORF72 mutations.