3-cyano-2-(trifluoromethyl)pyridine 1-oxide | 923288-82-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-cyano-2-(trifluoromethyl)pyridine 1-oxide
• 英文别名: 2-trifluoromethyl-1-oxy-3-pyridinecarbonitrile；1-oxido-2-(trifluoromethyl)pyridin-1-ium-3-carbonitrile
• CAS: 923288-82-8
• 化学式: C₇H₃F₃N₂O
• 分子量: 188.109
• InChiKey: PXUBPMXRIWOALZ-UHFFFAOYSA-N

物化性质

• 沸点：
  369.5±37.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  49.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-cyano-2-(trifluoromethyl)pyridine 1-oxide 在 水 、 羟胺 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以86%的产率得到2-(trifluoromethyl)nicotinamidoxime 1-oxide
  参考文献：
  名称：

  Discovery of a Long-Acting, Peripherally Selective Inhibitor of Catechol-O-methyltransferase

  摘要：

  Novel nitrocatechol-substituted heterocycles were designed and evaluated for their ability to inhibit catechol-O-methyltransferase (COMT). Replacement of the pyrazole core of the initial hit 4 with a 1,2,4-oxadiazole ring resulted in a series of compounds endowed with longer duration of COMT inhibition. Incorporation of a pyridine N-oxide residue at position 3 of the 1,2,4-oxadiazole ring led to analogue 37f, which was found to possess activity comparable to entacapone and lower toxicity in comparison to tolcapone. Lead structure 37f was systematically modified in order to improve selectivity and duration of COMT inhibition as well as to minimize toxicity. Oxadiazole 37d (2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide (BIA 9-1067)) was identified as a long-acting, purely peripheral inhibitor, which is currently under clinical evaluation as an adjunct to L-Dopa therapy of Parkinson's disease.

  DOI：

  10.1021/jm1001524
• 作为产物：
  描述：

  2-(三氟甲基)吡啶-3-甲腈 在 过氧化脲素 、 三氟乙酸酐 作用下， 以 二氯甲烷 为溶剂， 以41%的产率得到3-cyano-2-(trifluoromethyl)pyridine 1-oxide
  参考文献：
  名称：

  Discovery of a Long-Acting, Peripherally Selective Inhibitor of Catechol-O-methyltransferase

  摘要：

  Novel nitrocatechol-substituted heterocycles were designed and evaluated for their ability to inhibit catechol-O-methyltransferase (COMT). Replacement of the pyrazole core of the initial hit 4 with a 1,2,4-oxadiazole ring resulted in a series of compounds endowed with longer duration of COMT inhibition. Incorporation of a pyridine N-oxide residue at position 3 of the 1,2,4-oxadiazole ring led to analogue 37f, which was found to possess activity comparable to entacapone and lower toxicity in comparison to tolcapone. Lead structure 37f was systematically modified in order to improve selectivity and duration of COMT inhibition as well as to minimize toxicity. Oxadiazole 37d (2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide (BIA 9-1067)) was identified as a long-acting, purely peripheral inhibitor, which is currently under clinical evaluation as an adjunct to L-Dopa therapy of Parkinson's disease.

  DOI：

  10.1021/jm1001524

文献信息

• Nitrocatechol Derivatives as Comt Inhibitors
  申请人：Learmonth David Alexander

  公开号：US20090054437A1

  公开（公告）日：2009-02-26

  New compounds of formula I are described. The compounds have potentially valuable pharmaceutical properties in the treatment of some central and peripheral nervous system disorders.

  本文描述了一些公式I的新化合物。这些化合物在治疗某些中枢和周围神经系统疾病方面具有潜在的有价值的药物特性。
• NITROCATECHOL DERIVATIVES AS COMT INHIBITORS
  申请人：Learmonth David Alexander

  公开号：US20120196904A1

  公开（公告）日：2012-08-02

  New compounds of formula I are described. The compounds have potentially valuable pharmaceutical properties in the treatment of some central and peripheral nervous system disorders.

  本文描述了一种公式I的新化合物。这些化合物在治疗某些中枢和周围神经系统疾病方面具有潜在的有价值的药物特性。
• NOVEL PRECURSORS
  申请人：Learmonth David Alexander

  公开号：US20100292482A1

  公开（公告）日：2010-11-18

  The present invention relates to a Compound of the formula (I), wherein X represents CN, COOR, wherein R represents hydrogen or a carboxyl protecting group, CONR′2, wherein R′ represents hydrogen or a carboxyl protecting group, or nitro; R1, R2, R3, R4, R5 independently of each other represent hydrogen, C1-C6 alkyl, halogen, trifluoromethyl, cyano, nitro, substituted aryl or substituted heteroaryl group; Y represents hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl, C7-C13 alkaryl, trifluoromethyl, cyano, nitro, substituted aryl or substituted heteroaryl group; and wherein the stereochemically unspecified double bonds in the above formula (I) represent either the E,E; E,Z; Z,E or Z,Z configuration.

  本发明涉及一种化合物，其化学式为(I)，其中X代表CN、COOR，其中R代表氢或羧基保护基，CONR'2，其中R'代表氢或羧基保护基，或硝基；R1、R2、R3、R4、R5各自独立地代表氢、C1-C6烷基、卤素、三氟甲基、氰基、硝基、取代芳基或取代杂环基；Y代表氢、C1-C6烷基、C3-C7环烷基、C7-C13烷基芳基、三氟甲基、氰基、硝基、取代芳基或取代杂环基；其中上述化学式(I)中未明确立体化学的双键表示E,E；E,Z；Z,E或Z,Z构型。
• Nitrocatechol derivatives as COMT inhibitors
  申请人：BIAL—PORTELA & CA, S.A.

  公开号：US10336740B2

  公开（公告）日：2019-07-02

  New compounds of formula I are described. The compounds have potentially valuable pharmaceutical properties in the treatment of some central and peripheral nervous system disorders.

  本文描述了式 I 的新化合物。这些化合物在治疗某些中枢和周围神经系统疾病方面具有潜在的宝贵药用价值。
• WO2007/13830
  申请人：——

  公开号：——

  公开（公告）日：——