5'-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-6,2'-difluorobiphenyl-2-carbonitrile | 488799-60-6

• 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: 5'-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-6,2'-difluorobiphenyl-2-carbonitrile
• 英文别名: 6,2'-difluoro-5'-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)biphenyl-2-carbonitrile；2',6-difluoro-5'-(5,5-dimethyl[1,3,2]dioxaborinan-2-yl)biphenyl-2-carbonitrile；5'-(5,5-Dimethyl[1,3,2]dioxaborinan-2-yl)-6,2'-difluorobiphenyl-2-carbonitrile；2-[5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-fluorophenyl]-3-fluorobenzonitrile
• CAS: 488799-60-6
• 化学式: C₁₈H₁₆BF₂NO₂
• 分子量: 327.138
• InChiKey: HCFAZFACSDEUEL-UHFFFAOYSA-N

物化性质

• 沸点：
  465.6±45.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.27
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5'-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-6,2'-difluorobiphenyl-2-carbonitrile 在 1,4-bis(diphenylphosphinebutan)palladium dichloride sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 36.34h， 生成 6,2'-difluoro-5'-[6-(4-fluorophenyl)pyridazin-4-yl]biphenyl-2-carbonitrile
  参考文献：
  名称：

  [EN] PHENYLPYRIDAZINE DERIVATIVES AS LIGANDS FOR GABA RECEPTORS
  [FR] DERIVES DE PHENYLPYRIDAZINE UTILISES EN TANT QUE LIGANDS POUR DES RECEPTEURS GABA

  摘要：

  Formula (I)的4-苯基吡啶并衍生物是GABAA受体的选择性配体，特别是对其α2和/或α3和/或α5亚基具有高亲和力，因此在治疗和/或预防中枢神经系统的不良状况，包括焦虑、抽搐和认知障碍方面具有益处。

  公开号：

  WO2004014865A1
• 作为产物：
  描述：

  2-氨基-3-氟苯腈 在 potassium fluoride 、 tris-(dibenzylideneacetone)dipalladium(0) 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 三叔丁基膦 、 氢溴酸 、 potassium acetate 、 二甲基亚砜 、 tin(ll) chloride 、 sodium nitrite 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 反应 47.58h， 生成 5'-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-6,2'-difluorobiphenyl-2-carbonitrile
  参考文献：
  名称：

  Discovery of Imidazo[1,2-b][1,2,4]triazines as GABA_A α2/3 Subtype Selective Agonists for the Treatment of Anxiety

  摘要：

  The identification of a series of imidazo[1,2-b][1,2,4]triazines with high affinity and functional selectivity for the GABA(A) alpha 3-containing receptor subtype is described, leading to the identification of a clinical candidate, 11. Compound 11 shows good bioavailability and half-life in preclinical species, and it is a nonsedating anxiolytic in both rat and squirrel monkey behavioral models.

  DOI：

  10.1021/jm051200u

文献信息

• [EN] FLUOROIMIDAZOPYRIMIDINES AS GABA-A ALPHA 2/3 LIGANDS FOR DEPRESSION/ANXIETY<br/>[FR] ANTIDEPRESSEUR / ANXIOLITIQUES A BASE DE FLUOROIMIDAZOPYRIMIDINES SERVANT DE LIGANDS ALPHA 2/3 DES GABA-A
  申请人：MERCK SHARP & DOHME

  公开号：WO2004065388A1

  公开（公告）日：2004-08-05

  The present invention provides a compound formula (I), or a pharmaceutically acceptable salt thereof: wherein W is phenyl or pyridyl; X1 represents hydrogen, halogen, C1-6 alkyl, trifluoromethyl or C1-6 alkoxy; X2 represents hydrogen or halogen; Y represents a chemical bond, an -NH- linkage or a group -OCnH2n-; Z represents an optionally substituted aryl or heteroaryl group; R1 represents hydrocarbon, a heterocyclic group, halogen, cyano, trifluoromethyl, nitro, -ORa, -SRa, -SORa, -SO2Ra, -SO2NRaRb, NRaRb, -NRaCORb, -NRaCO2Rb, -CORa, -CO2Ra, -CONRaRb or Cra=NORb; Ra and Rb independently represent hydrogen, hydrocarbon or a heterocyclic group; and n is zero, one, two or three; pharmaceutical compositions comprising it; its use in methods of treatment; use of it in the manufacture of medicaments to treat anxiety and/or depression; and methods of treatment for anxiety and/or depression using it.

  本发明提供了一个化合物公式(I)，或其药学上可接受的盐：其中W是苯基或吡啶基；X1代表氢、卤素、C1-6烷基、三氟甲基或C1-6烷氧基；X2代表氢或卤素；Y代表化学键、-NH-连接或-OCnH2n-基团；Z代表可选择取代的芳基或杂芳基；R1代表碳氢化合物、杂环基团、卤素、氰基、三氟甲基、硝基、-ORa、-SRa、-SORa、-SO2Ra、-SO2NRaRb、NRaRb、-NRaCORb、-NRaCO2Rb、-CORa、-CO2Ra、-CONRaRb或Cra=NORb；Ra和Rb独立地代表氢、碳氢化合物或杂环基团；n为零、一、二或三；包括它的药物组合物；其在治疗方法中的使用；将其用于制造治疗焦虑和/或抑郁症药物；以及使用它进行焦虑和/或抑郁症治疗的方法。
• (1, 8) naphthyridines as gaba ligands, their pharmaceutical compositions and uses
  申请人：——

  公开号：US20040171633A1

  公开（公告）日：2004-09-02

  A class of [1,8] naphthyridine analogues which are substituted in the 4-position by a substituted phenyl ring. These compounds are ligands for GABA A receptors and useful in the therapy of deleterious mental states such as anxiety.

  这是一类1,8-萘啶类似物，其4位被取代的苯基环。这些化合物是GABAA受体的配体，可用于治疗焦虑等有害精神状态。
• (1,8) naphthyridines as gaba ligands, their pharmaceutical compositions and uses
  申请人：Carling William Robert

  公开号：US06960598B2

  公开（公告）日：2005-11-01

  A class of [1,8] naphthyridine analogues which are substituted in the 4-position by a substituted phenyl ring. These compounds are ligands for GABA A receptors and useful in the therapy of deleterious mental states such as anxiety.

  一类[1,8]萘啶类似物，其4位被取代苯基环所取代。这些化合物是GABAA受体的配体，对治疗焦虑等有害精神状态有用。
• Discovery of Imidazo[1,2-<i>b</i>][1,2,4]triazines as GABA_A α2/3 Subtype Selective Agonists for the Treatment of Anxiety
  作者：Michael G. N. Russell、Robert W. Carling、Leslie J. Street、David J. Hallett、Simon Goodacre、Elena Mezzogori、Michael Reader、Susan M. Cook、Frances A. Bromidge、Robert Newman、Alison J. Smith、Keith A. Wafford、George R. Marshall、David S. Reynolds、Rebecca Dias、Pushpindar Ferris、Jo Stanley、Rachael Lincoln、Spencer J. Tye、Wayne F. A. Sheppard、Bindi Sohal、Andrew Pike、Maria Dominguez、John R. Atack、José L. Castro

  DOI：10.1021/jm051200u

  日期：2006.2.1

  The identification of a series of imidazo[1,2-b][1,2,4]triazines with high affinity and functional selectivity for the GABA(A) alpha 3-containing receptor subtype is described, leading to the identification of a clinical candidate, 11. Compound 11 shows good bioavailability and half-life in preclinical species, and it is a nonsedating anxiolytic in both rat and squirrel monkey behavioral models.
• [EN] PHENYLPYRIDAZINE DERIVATIVES AS LIGANDS FOR GABA RECEPTORS<br/>[FR] DERIVES DE PHENYLPYRIDAZINE UTILISES EN TANT QUE LIGANDS POUR DES RECEPTEURS GABA
  申请人：MERCK SHARP & DOHME

  公开号：WO2004014865A1

  公开（公告）日：2004-02-19

  A class of 4-phenylpyridazine derivatives of Formula (I), being selective ligands for GABAA receptors, in particular having high affinity for the α2 and/or α3 and or α5 subunit thereof, are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.

  Formula (I)的4-苯基吡啶并衍生物是GABAA受体的选择性配体，特别是对其α2和/或α3和/或α5亚基具有高亲和力，因此在治疗和/或预防中枢神经系统的不良状况，包括焦虑、抽搐和认知障碍方面具有益处。