1-cyano-1-(2,4-dichlorophenyl)propan-2-one | 76562-15-7

• 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: 1-cyano-1-(2,4-dichlorophenyl)propan-2-one
• 英文别名: 2-(2,4-dichloro-phenyl)-acetoacetonitrile；2-(2,4-Dichlor-phenyl)-acetoacetonitril；2-(2,4-Dichlorophenyl)-3-oxobutanenitrile
• CAS: 76562-15-7
• 化学式: C₁₀H₇Cl₂NO
• 分子量: 228.078
• InChiKey: WUGKLBPNRZUFNG-UHFFFAOYSA-N

物化性质

• 沸点：
  302.7±37.0 °C(Predicted)
• 密度：
  1.338±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  40.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-cyano-1-(2,4-dichlorophenyl)propan-2-one 在 sodium ethanolate 、 一水合肼 、 溶剂黄146 、 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 乙醇 、 甲苯 、 乙腈 为溶剂， 反应 50.0h， 生成 4-chloro-2,7-dimethyl-8-(2,4-dichlorophenyl)[1,5-a]pyrazolo-1,3,5-triazine
  参考文献：
  名称：

  4-(1,3-Dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)pyrazolo[1,5-a]-1,3,5-triazine:  A Potent, Orally Bioavailable CRF₁ Receptor Antagonist

  摘要：

  Structure-activity studies; in the pyrazolo[1,5-a]-1,3,5-triazine series led to the discovery that compound 11i (DMP696) is a potent hCRF(1) receptor antagonist (K-i = 1.7 nM vs 7.5 nM for alpha-hel-CRF(9-41), hCRF(1) adenylate cyclase IC50 = 82 nM vs 286 nM for alpha-hel-CRF(9-41)). Compound 11i has excellent oral pharmacokinetic profiles in rats and dogs (37% and 50% oral bioavailabilities, respectively). This compound displays good activity in the rat situational anxiety model (MED = 3 mg/kg (po)), whereas a literature standard 1 (CP154526-1) was inactive (MED > 30 mg/kg (po)). Analogue 11i reduced stereotypical mouth movements in rhesus monkeys by 50% at 21 mg/kg (po) using the human intruder paradigm. Overall, the profile of pyrazolotriazine 11i indicates that hCRF1 receptor antagonists may be anxiolytic agents, which have reduced motor side effect profiles.

  DOI：

  10.1021/jm9904351
• 作为产物：
  描述：

  2,4-二氯苯乙腈 、 乙酸乙酯 在 sodium 作用下， 反应 1.0h， 以70%的产率得到1-cyano-1-(2,4-dichlorophenyl)propan-2-one
  参考文献：
  名称：

  4-(1,3-Dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)pyrazolo[1,5-a]-1,3,5-triazine:  A Potent, Orally Bioavailable CRF₁ Receptor Antagonist

  摘要：

  Structure-activity studies; in the pyrazolo[1,5-a]-1,3,5-triazine series led to the discovery that compound 11i (DMP696) is a potent hCRF(1) receptor antagonist (K-i = 1.7 nM vs 7.5 nM for alpha-hel-CRF(9-41), hCRF(1) adenylate cyclase IC50 = 82 nM vs 286 nM for alpha-hel-CRF(9-41)). Compound 11i has excellent oral pharmacokinetic profiles in rats and dogs (37% and 50% oral bioavailabilities, respectively). This compound displays good activity in the rat situational anxiety model (MED = 3 mg/kg (po)), whereas a literature standard 1 (CP154526-1) was inactive (MED > 30 mg/kg (po)). Analogue 11i reduced stereotypical mouth movements in rhesus monkeys by 50% at 21 mg/kg (po) using the human intruder paradigm. Overall, the profile of pyrazolotriazine 11i indicates that hCRF1 receptor antagonists may be anxiolytic agents, which have reduced motor side effect profiles.

  DOI：

  10.1021/jm9904351

文献信息

• 3-Amino- and 5-Aminopyrazoles with Anticonvulsant Activity
  作者：Hans-Joachim Lankau、Manfred Menzer、Angelika Rostock、Thomas Arnold、Chris Rundfeldt、Klaus Unverferth

  DOI：10.1002/(sici)1521-4184(19996)332:6<219::aid-ardp219>3.0.co;2-t

  日期：1999.6

  New 3‐amino‐ and 5‐aminopyrazoles were synthesised. 3‐Aminopyrazoles exert a strong anticonvulsant effect. 4‐Chlorophenyl‐3‐( morpholin‐4‐yl)‐1H‐pyrazole 2 distinctively blocks sodium channels and is strongly effective in the Maximal Electroshock Seizure (MES) test.

  合成了新的 3-氨基和 5-氨基吡唑。3-氨基吡唑类药物具有很强的抗惊厥作用。4 - Chlorophenyl - 3- (morpholin - 4-yl) -1H - pyrazole 2 独特地阻断钠通道并且在最大电休克癫痫 (MES) 测试中非常有效。
• Certain 2,4-diamino-5-(2,3-dihalophenyl)-6-substituted pyrimidines which
  申请人：Glaxo Wellcome Inc.

  公开号：US05597828A1

  公开（公告）日：1997-01-28

  A class of substituted phenylpyrimidine compounds are disclosed which are potent inhibitors of the excitatory amino acid, glutamate. Such compounds are useful in the treatment or prevention of a range of CNS disorders including cerebral ischaemic damage and epilepsy.

  本文披露了一类取代苯基嘧啶化合物，它们是激动性氨基酸谷氨酸的有效抑制剂。这样的化合物在治疗或预防一系列中枢神经系统疾病方面非常有用，包括脑缺血性损伤和癫痫。
• Treatment of injury of the spinal cord or brain using
  申请人：——

  公开号：US05597827A1

  公开（公告）日：1997-01-28

  A class of substituted phenylpyrimidine compounds are disclosed which are potent inhibitors of the excitatory amino acid, glutamate. Such compounds are useful in the treatment or prevention of a range of CNS disorders including cerebral ischaemic damage and epilepsy.

  本文披露了一类取代苯基嘧啶化合物，它们是兴奋性氨基酸谷氨酸的强效抑制剂。这些化合物可用于治疗或预防一系列中枢神经系统疾病，包括脑缺血性损伤和癫痫。
• Pharmacologically active CNS compounds
  申请人：Glaxo Wellcome Inc.

  公开号：US05635507A1

  公开（公告）日：1997-06-03

  A class of substituted phenylpyrimidine compounds are disclosed which are potent inhibitors of the excitatory amino acid, glutamate. Such compounds are useful in the treatment or prevention of a range of CNS disorders including cerebral ischaemic damage and epilepsy.

  本文披露了一类取代苯基嘧啶化合物，它们是兴奋性氨基酸谷氨酸的有效抑制剂。这些化合物可用于治疗或预防一系列中枢神经系统疾病，包括脑缺血性损伤和癫痫。
• 2-(n-alkylpiperazino or morpholino)-4-amino-5-aryl-pyrimidines
  申请人：Glaxo Wellcome Inc.

  公开号：US05712276A1

  公开（公告）日：1998-01-27

  A class of substituted phenylpyrimidine compounds are disclosed which are potent inhibitors of the excitatory amino acid, glutamate. Such compounds are useful in the treatment or prevention of a range of CNS disorders including cerebral ischaemic damage and epilepsy.

  公开了一类取代苯基嘧啶化合物，它们是谷氨酸兴奋性氨基酸的有效抑制剂。这些化合物在治疗或预防包括脑缺血损伤和癫痫在内的一系列中枢神经系统疾病中有用。