6-(溴甲基)-2-硝基苯甲腈 | 50828-01-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 6-(溴甲基)-2-硝基苯甲腈
• 英文名称: 6-(bromomethyl)-2-nitrobenzenecarbonitrile
• 英文别名: 2-bromomethyl-6-nitrobenzonitrile；2-(Bromomethyl)-6-nitrobenzonitrile
• CAS: 50828-01-8
• 化学式: C₈H₅BrN₂O₂
• 分子量: 241.044
• InChiKey: IAIPMOHBQALPDC-UHFFFAOYSA-N

物化性质

• 沸点：
  382.2±32.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  69.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(溴甲基)-2-硝基苯甲腈 在 吗啉 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 生成 6-(morpholin-4-ylmethyl)-2-nitrobenzenecarbonitrile
  参考文献：
  名称：

  2-oxo-1,3,4-trihydroquinazolinyl derivatives and methods of use

  摘要：

  选定的化合物对于治疗疾病，如细胞增殖或凋亡介导的疾病，具有有效性。该发明涵盖了新颖的化合物、类似物、前药和其药学上可接受的衍生物，药物组合物以及预防和治疗涉及中风、癌症等疾病和其他疾病或病症的方法。该发明还涉及制备这些化合物的方法，以及在这些方法中有用的中间体。

  公开号：

  US20030229068A1
• 作为产物：
  描述：

  6-硝基-2-甲基苯甲腈 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 作用下， 以 四氯化碳 为溶剂， 以66%的产率得到6-(溴甲基)-2-硝基苯甲腈
  参考文献：
  名称：

  Structure–activity relationships of 3,4-dihydro-1H-quinazolin-2-one derivatives as potential CDK5 inhibitors

  摘要：

  Cyclin-dependent kinase 5 (CDK5) is a serine/threonine kinase that plays a critical role in the early development of the nervous system. Deregulation of CDK5 is believed to contribute to the abnormal phosphorylation of various cellular substrates associated with neurodegenerative disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, and ischemic stroke. Acyclic urea 3 was identified as a potent CDK5 inhibitor and co-crystallographic data of urea 3/CDK2 enzyme were used to design a novel series of 3,4-dihydroquinazolin-2(1H)-ones as CDK5 inhibitors. In this investigation we present our synthetic studies toward this series of compounds and discuss their biological relevance as CDK5 inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.07.005

文献信息

• [EN] 2,4-DIAMINOQUINAZOLINES FOR SPINAL MUSCULAR ATROPHY<br/>[FR] 2,4-DIAMINOQUINAZOLINES UTILES POUR LE TRAITEMENT D'UNE ATROPHIE MUSCULAIRE SPINALE
  申请人：DECODE CHEMISTRY INC

  公开号：WO2005123724A1

  公开（公告）日：2005-12-29

  2,4-Diaminoquinazolines of formulae I-IV and VI (I, II, III, IV and VI) are useful for treating spinal muscular atrophy (SMA).

  2,4-二氨基喹唑啉的化学式I-IV和VI（I，II，III，IV和VI）可用于治疗脊髓性肌萎缩症（SMA）。
• 2,4-diaminoquinazolines for spinal muscular atrophy
  申请人：Singh Jasbir

  公开号：US20050288314A1

  公开（公告）日：2005-12-29

  2,4-Diaminoquinazolines of formulae I-IV and VI are useful for treating spinal muscular atrophy (SMA).

  公式I-IV和VI的2,4-二氨基喹唑啉可用于治疗脊髓肌肉萎缩症(SMA)。
• 2,4-Diaminoquinazolines for Spinal Muscular Atrophy
  申请人：Singh Jasbir

  公开号：US20110112118A1

  公开（公告）日：2011-05-12

  2,4-Diaminoquinazolines of formulae I-IV and VI are useful for treating spinal muscular atrophy (SMA).

  公式I-IV和VI的2,4-二氨基喹唑啉化合物可用于治疗脊髓性肌萎缩症（SMA）。
• 2,4-Diaminoquinazolines for spinal muscular atrophy
  申请人：Singh Jasbir

  公开号：US09067897B2

  公开（公告）日：2015-06-30

  2,4-Diaminoquinazolines of formulae I-IV and VI are useful for treating spinal muscular atrophy (SMA).

  公式I-IV和VI的2,4-二氨基喹唑啉可用于治疗脊髓肌肉萎缩症（SMA）。
• Synthesis and Biological Evaluation of Novel 2,4-Diaminoquinazoline Derivatives as <i>SMN2</i> Promoter Activators for the Potential Treatment of Spinal Muscular Atrophy
  作者：John Thurmond、Matthew E. R. Butchbach、Marty Palomo、Brian Pease、Munagala Rao、Louis Bedell、Monica Keyvan、Grace Pai、Rama Mishra、Magnus Haraldsson、Thorkell Andresson、Gisli Bragason、Margret Thosteinsdottir、Jon Mar Bjornsson、Daniel D. Coovert、Arthur H. M. Burghes、Mark E. Gurney、Jasbir Singh

  DOI：10.1021/jm061475p

  日期：2008.2.1

  Proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by death of motor neurons in the spinal cord that is caused by deletion and/or mutation of the survival motor neuron gene (SMN1). Adjacent to SMN1 are a variable number of copies of the SMN2 gene. The two genes essentially differ by a single nucleotide, which causes the majority of the RNA transcripts from SMN2 to lack exon 7. Although both SMN1 and SMN2 encode the same Smn protein amino acid sequence, the loss of SMN1 and incorrect splicing of SMN2 have the consequence that Smn protein levels are insufficient for the survival of motor neurons. The therapeutic goal of our medicinal chemistry effort was to identify small-molecule activators of the SMN2 promoter that, by up-regulating gene transcription, would produce greater quantities of full-length Smn protein. Our initial medicinal chemistry effort explored a series of C5 substituted benzyl ether based 2,4-diaminoquinazoline derivatives that were found to be potent activators of the SMN2 promoter; however, inhibition of DHFR was shown to be an off-target activity that was linked to ATP depletion. We used a structure-guided approach to overcome DHFR inhibition while retaining SMN2 promoter activation. A lead compound 11a was identified as having high potency (EC50 = 4 nM) and 2.3-fold induction of the SMN2 promoter. Compound Ila possessed desirable pharmaceutical properties, including excellent brain exposure and long brain half-life following oral dosing to mice. The piperidine compound Ila up-regulated expression of the mouse SMN gene in NSC-34 cells, a mouse motor neuron hybrid cell line. In type I SMA patient fibroblasts, compound Ila induced Smn in a dose-dependent manner when analyzed by immuno-blotting and increased the number of intranuclear particles called gems. The compound restored gems numbers in type I SMA patient fibroblasts to levels near unaffected genetic carriers of SMA.