2-氯-6-(2,4-二氯苯基)烟腈 | 946384-97-0

• 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
• 中文名称: 2-氯-6-(2,4-二氯苯基)烟腈
• 英文名称: 2-chloro-6-(2,4-dichlorophenyl)nicotinonitrile
• 英文别名: 2-chloro-6-(2,4-dichlorophenyl)pyridine-3-carbonitrile
• CAS: 946384-97-0
• 化学式: C₁₂H₅Cl₃N₂
• 分子量: 283.544
• InChiKey: KAMITLQYGOMUFU-UHFFFAOYSA-N

物化性质

• 沸点：
  410.5±45.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  36.7
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  2-氯-6-(2,4-二氯苯基)烟腈 在 2-氰基乙硫醇 、 potassium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.75h， 生成 (E)-N'-(2-cyano-6-(2,4-dichlorophenyl)thieno[2,3-b]pyridin-3-yl)-N,N-dimethylformimidamide
  参考文献：
  名称：

  Synthesis and molecular modelling studies of 8-arylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4-amines as multitarget Ser/Thr kinases inhibitors

  摘要：

  This paper reports the design and synthesis of a novel series of 8-arylpyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amines via microwave-assisted multi-step synthesis. A common precursor of the whole series, 3-amino-5-bromothieno[2,3-b]pyridine-2-carbonitrile, was rapidly synthesized in one step from commercially-available 5-bromo-2-chloronicotinonitrile. Formylation with DMF-DMA led to (E)-N'-(5-bromo-2-cyanothieno[2,3-b]pyridin-3-yl)-N,N-dimethylformimidamide (4) which was conveniently functionalized at position 8 by palladium-catalyzed Suzuki-Miyaura cross-coupling to introduce a heteroaromatic ring. High-temperature formamide-mediated cyclization of the cyanoamidine intermediate gave seventeen 8-arylpyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amines. The inhibitory potency of the final products was evaluated against five protein kinases (CDK5/p25, CK1 delta/epsilon, GSK3 alpha/beta, DYRK1A and CLK1) and revealed that 8-(2,4-dichlorophenyppyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amine 1g specifically inhibits CK1 delta/epsilon and CLK1 (220 and 88 nM, respectively) while its 7-(2,4-dichlorophenyl) pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amine isomer 10 showed no activity on the panel of tested kinases. Molecular modelling of 10 and 1g in the ATP binding sites of CK1 delta/epsilon and CLK1 showed that functionalization at position 7 of pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amines is likely to induce a steric clash on the CK1 delta/epsilon P-loop and thus a complete loss of inhibitory activity. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.038
• 作为产物：
  描述：

  2,6-二氯烟腈 、 2,4-二氯苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 以87%的产率得到2-氯-6-(2,4-二氯苯基)烟腈
  参考文献：
  名称：

  Synthesis and molecular modelling studies of 8-arylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4-amines as multitarget Ser/Thr kinases inhibitors

  摘要：

  This paper reports the design and synthesis of a novel series of 8-arylpyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amines via microwave-assisted multi-step synthesis. A common precursor of the whole series, 3-amino-5-bromothieno[2,3-b]pyridine-2-carbonitrile, was rapidly synthesized in one step from commercially-available 5-bromo-2-chloronicotinonitrile. Formylation with DMF-DMA led to (E)-N'-(5-bromo-2-cyanothieno[2,3-b]pyridin-3-yl)-N,N-dimethylformimidamide (4) which was conveniently functionalized at position 8 by palladium-catalyzed Suzuki-Miyaura cross-coupling to introduce a heteroaromatic ring. High-temperature formamide-mediated cyclization of the cyanoamidine intermediate gave seventeen 8-arylpyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amines. The inhibitory potency of the final products was evaluated against five protein kinases (CDK5/p25, CK1 delta/epsilon, GSK3 alpha/beta, DYRK1A and CLK1) and revealed that 8-(2,4-dichlorophenyppyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amine 1g specifically inhibits CK1 delta/epsilon and CLK1 (220 and 88 nM, respectively) while its 7-(2,4-dichlorophenyl) pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amine isomer 10 showed no activity on the panel of tested kinases. Molecular modelling of 10 and 1g in the ATP binding sites of CK1 delta/epsilon and CLK1 showed that functionalization at position 7 of pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amines is likely to induce a steric clash on the CK1 delta/epsilon P-loop and thus a complete loss of inhibitory activity. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.038

文献信息

• [EN] INHIBITORS OF TRYPTOPHAN DIOXYGENASES (IDO1 AND TDO) AND THEIR USE IN THERAPY<br/>[FR] INHIBITEURS DE TRYPTOPHANE DIOXYGÉNASES (IDO1 ET TDO) ET LEUR UTILISATION EN THÉRAPIE
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2016024233A1

  公开（公告）日：2016-02-18

  Pharmaceutical compositions comprising 3-aminoisoxazolopyridine compounds of the Formula I having IDO1 and/or TDO inhibitory activity are described, where W is CR1, N or N-oxide; X is CR2, N or N-oxide; Y is CR3, N or N-oxide; Z is CR4, N or N-oxide; and at least one of W, X, Y, and Z is N or N-oxide; and R9 and R10 are as defined. Also described are methods of using such compounds in the treatment of various conditions, such as cancer.

  描述了包含具有IDO1和/or TDO抑制活性的3-氨基异恶唑啉化合物I的药物组合物，其中W是CR1，N或N-氧化物；X是CR2，N或N-氧化物；Y是CR3，N或N-氧化物；Z是CR4，N或N-氧化物；W、X、Y和Z中的至少一个是N或N-氧化物；R9和R10如所定义。还描述了使用这些化合物治疗各种疾病，如癌症的方法。
• Substituted pyridines, and use thereof as Gsk3 inhibitors
  申请人：Siegel Stephan

  公开号：US20110190316A1

  公开（公告）日：2011-08-04

  The invention relates to substituted pyridines and to processes for preparation thereof, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of haematological disorders, preferably of leukopenia and neutropenia.

  本发明涉及取代吡啶及其制备方法，以及用于生产用于治疗和/或预防疾病，特别是血液学疾病，尤其是白细胞减少症和粒细胞减少症的药物的应用。
• Substituted pyridines, and use thereof as GSK3 inhibitors
  申请人：Siegel Stephan

  公开号：US08664246B2

  公开（公告）日：2014-03-04

  The invention relates to substituted pyridines and to processes for preparation thereof, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of haematological disorders, preferably of leukopenia and neutropenia.

  本发明涉及取代吡啶及其制备方法，以及用于制备治疗和/或预防疾病的药物的用途，特别是用于治疗血液疾病，优选为白细胞减少症和中性粒细胞减少症。
• Inhibitors of tryptophan dioxygenases (IDO1 and TDO) and their use in therapy
  申请人：AUCKLAND UNISERVICES LIMITED

  公开号：US10888567B2

  公开（公告）日：2021-01-12

  Pharmaceutical compositions comprising 3-aminoisoxazolopyridine compounds of the Formula I having IDO1 and/or TDO inhibitory activity are described, where W is CR1, N or N-oxide; X is CR2, N or N-oxide; Y is CR3, N or N-oxide; Z is CR4, N or N-oxide; and at least one of W, X, Y, and Z is N or N-oxide; and R9 and R10 are as defined. Also described are methods of using such compounds in the treatment of various conditions, such as cancer.

  描述了包含具有 IDO1 和/或 TDO 抑制活性的式 I 的 3-氨基异噁唑吡啶化合物的药物组合物，其中 W 是 CR1、N 或 N-氧化物；X 是 CR2、N 或 N-氧化物；Y 是 CR3、N 或 N-氧化物；Z 是 CR4、N 或 N-氧化物；W、X、Y 和 Z 中至少有一个是 N 或 N-氧化物；R9 和 R10 如所定义。 还描述了使用此类化合物治疗各种疾病（如癌症）的方法。
• SUBSTITUIERTE PYRIDINE UND IHRE VERWENDUNG ALS GSK3 INHIBITOREN
  申请人：Bayer Intellectual Property GmbH

  公开号：EP2326639B1

  公开（公告）日：2015-08-19