2-fluoro-6-(4-methoxybenzyloxy) benzonitrile | 1009734-27-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-fluoro-6-(4-methoxybenzyloxy) benzonitrile
• 英文别名: 2-Fluoro-6-[(4-methoxybenzyl)oxy]benzonitrile；2-fluoro-6-[(4-methoxyphenyl)methoxy]benzonitrile
• CAS: 1009734-27-3
• 化学式: C₁₅H₁₂FNO₂
• 分子量: 257.264
• InChiKey: UYPMJWFZFLMAPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-fluoro-6-(4-methoxybenzyloxy) benzonitrile 、 碳酸胍 以 异丁酰胺 为溶剂， 反应 5.0h， 生成 5-(4-methoxybenzyloxy)quinazoline-2,4-diamine
  参考文献：
  名称：

  [EN] 2,4-DIAMINOQUINAZOLINES FOR SPINAL MUSCULAR ATROPHY
  [FR] 2,4-DIAMINOQUINAZOLINES UTILES POUR LE TRAITEMENT D'UNE ATROPHIE MUSCULAIRE SPINALE

  摘要：

  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）。

  公开号：

  WO2005123724A1
• 作为产物：
  描述：

  2,6-二氟苯腈 、 4-甲氧基苄醇 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 2-fluoro-6-(4-methoxybenzyloxy) benzonitrile
  参考文献：
  名称：

  [EN] PYRIMIDOPYRIMIDOINDAZOLE DERIVATIVE
  [FR] DÉRIVÉ DE PYRIMIDO-PYRIMIDO-INDAZOLE

  摘要：

  这项发明是为了提供一种新型的抗癌药物或增敏剂，用于癌症化疗或放疗。通式(I)的化合物：其中A表示芳基或杂环基，或者是式(a)的基团；R1表示-(C=O)aOb(C1-C6)烷基、-(C=O)aOb(C2-C6)烯基、-(C=O)aOb(C3-C6)环烷基、芳基或杂环基；R2和R3各自表示氢原子、卤素原子、羟基、羧基、-(C=O)aOb(C1-C6)烷基或-(C=O)aN(R1e)R2e的基团；R4表示氢原子或(C1-C6)烷基等，具有优异的Wee1激酶抑制作用，因此在医学领域特别是各种癌症治疗领域中非常有用。

  公开号：

  WO2010098367A1

文献信息

• Pyrimidopyrimidoindazole derivative
  申请人：MSDKK

  公开号：US08288396B2

  公开（公告）日：2012-10-16

  The invention is to provide a novel anticancer agent or sensitizer for cancer chemotherapy or radiotherapy. A compound of a general formula (I): wherein A means an aryl group or a heteroaryl group, or a group of a formula (a): R1 means a —(C═O)aOb(C1-C6)alkyl group, a —(C═O)aOb(C2-C6)alkenyl group, a —(C═O)aOb(C3-C6)cycloalkyl group, an aryl group or a heteroaryl group; R2 and R3 each mean a hydrogen atom, a halogen atom, a hydroxyl group, a carboxyl group, a —(C═O)aOb(C1-C6)alkyl group or a group of —(C═O)aN(R1e)R2e; R4 means a hydrogen atom or a (C1-C6)alkyl group, and the like have an excellent Wee1-kinase-inhibitory effect, and are therefore useful in the field of medicine, especially in the field of various cancer treatments.

  该发明提供了一种用于癌症化疗或放疗的新型抗癌剂或增敏剂。该化合物具有以下通式（I）：其中A表示芳基或杂环基，或公式（a）中的基团：R1表示-（C═O）aOb（C1-C6）烷基，-（C═O）aOb（C2-C6）烯基，-（C═O）aOb（C3-C6）环烷基，芳基或杂环基；R2和R3分别表示氢原子，卤素原子，羟基，羧基，-（C═O）aOb（C1-C6）烷基或-（C═O）aN（R1e）R2e基团；R4表示氢原子或（C1-C6）烷基等。该化合物具有出色的Wee1激酶抑制作用，因此在医学领域，特别是各种癌症治疗领域中得到了广泛应用。
• PYRIMIDOPYRIMIDOINDAZOLE DERIVATIVE
  申请人：Goto Yasuhiro

  公开号：US20120134955A1

  公开（公告）日：2012-05-31

  The invention is to provide a novel anticancer agent or sensitizer for cancer chemotherapy or radiotherapy. A compound of a general formula (I): wherein A means an aryl group or a heteroaryl group, or a group of a formula (a):; R 1 means a —(C═O) a O b (C1-C6)alkyl group, a —(C═O) a O b (C2-C6)alkenyl group, a —(C═O) a O b (C3-C6)cycloalkyl group, an aryl group or a heteroaryl group; R 2 and R 3 each mean a hydrogen atom, a halogen atom, a hydroxyl group, a carboxyl group, a —(C═O) a O b (C1-C6)alkyl group or a group of —(C═O) a N(R 1e )R 2e ; R 4 means a hydrogen atom or a (C1-C6)alkyl group, and the like have an excellent Wee 1-kinase-inhibitory effect, and are therefore useful in the field of medicine, especially in the field of various cancer treatments.

  本发明提供一种新型的抗癌剂或增敏剂，用于癌症化疗或放疗。该化合物的一般式（I）如下：其中，A表示芳基或杂环基，或式（a）的基团；R1表示—（C═O）aOb（C1-C6）烷基，—（C═O）aOb（C2-C6）烯基，—（C═O）aOb（C3-C6）环烷基，芳基或杂环基；R2和R3各表示氢原子、卤素原子、羟基、羧基、—（C═O）aOb（C1-C6）烷基或—（C═O）aN（R1e）R2e基团；R4表示氢原子或（C1-C6）烷基等。该化合物具有出色的Wee 1-激酶抑制作用，因此在医学领域，特别是各种癌症治疗领域中非常有用。
• 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.
• US8288396B2
  申请人：——

  公开号：US8288396B2

  公开（公告）日：2012-10-16