d4-4-chlorobenzotrifluoride | 1219804-33-7

• 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: d4-4-chlorobenzotrifluoride
• 英文别名: 4-Chlorobenzotrifluoride-d4；1-chloro-2,3,5,6-tetradeuterio-4-(trifluoromethyl)benzene
• CAS: 1219804-33-7
• 化学式: C₇H₄ClF₃
• 分子量: 184.525
• InChiKey: QULYNCCPRWKEMF-RHQRLBAQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  11
• 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：
  0
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  d4-4-chlorobenzotrifluoride 、 d10-(R)-3-amino-1-phenylpropane-1-ol 在 sodium hydride 作用下， 以 二甲基亚砜 为溶剂， 反应 1.5h， 生成 d14-(R)-3-phenyl-3-(4-trifluoromethylphenoxy)-propylamine
  参考文献：
  名称：

  WO2007/62119

  摘要：

  公开号：

文献信息

• Potent Inhibition of Alcohol Self-Administration in Alcohol-Preferring Rats by a <i>κ</i>-Opioid Receptor Antagonist
  作者：John R. Cashman、Marc R. Azar

  DOI：10.1124/jpet.114.214262

  日期：2014.7

  A substituted aryl amide derivative of 6-naltrexamine—17-cyclopropylmethyl-3,14 β -dihydroxy-4,5 α -epoxy-6 β -[(4′-trimethylfluoro)benzamido]morphinan-hydrochloride—(compound 5 ), previously shown to be a potent κ -opioid receptor antagonist, was used to characterize the physicochemical properties and efficacy to decrease alcohol self-administration in alcohol-preferring rats (P-rats) and binge-like P-rats. Previous studies showed that compounds closely related to compound 5 possessed favorable properties regarding penetration of the blood-brain barrier. Pharmacokinetic studies showed that compound 5 had acceptable bioavailability. In contrast to other κ -receptor antagonists, in particular norbinaltorphimine, compound 5 showed favorable drug-like properties. Based on these findings, further studies were done. Safety studies showed that compound 5 was not hepatotoxic at doses 200-fold greater than an efficacious dose. The effects of compound 5 or naltrexone on the hepatotoxicity of thiobenzamide were investigated. In contrast to naltrexone, which exacerbated thiobenzamide-mediated hepatotoxicity, compound 5 was observed to be hepatoprotective. Based on the physicochemical properties of compound 5 , the compound was examined in rat animal models of alcohol self-administration. The inhibition of ethanol self-administration by compound 5 in alcohol-dependent and alcohol-nondependent P-rats trained to self-administer a 10% (w/v) ethanol solution, using operant techniques, showed very potent efficacy (i.e., estimated ED50 values of 4–5 μ g/kg). In a binge-like P-rat animal model, inhibition of alcohol self-administration by compound 5 had an estimated ED50 value of 8 μ g/kg. The results suggest that compound 5 is a potent drug-like κ -opioid receptor antagonist of utility in alcohol cessation medications development.

  6-naltrexamine-17-cyclopropylmethyl-3,14 β -dihydroxy-4,5 α -epoxy-6 β -[(4′-trimethylfluoro)benzamido]morphinan-hydrochloride- （化合物 5）的取代芳基酰胺衍生物、以前的研究表明，该化合物是一种强效的κ-阿片受体拮抗剂，研究人员利用该化合物来鉴定其理化性质以及降低酒精偏好大鼠（P-rats）和狂饮型 P-rats的酒精自我给药的功效。以前的研究表明，与化合物 5 密切相关的化合物在穿透血脑屏障方面具有良好的特性。药代动力学研究表明，化合物 5 具有可接受的生物利用度。与其他κ受体拮抗剂（尤其是诺比纳托啡）相比，化合物 5 具有良好的类药物特性。基于这些发现，我们进行了进一步的研究。安全性研究表明，在剂量比有效剂量大 200 倍的情况下，化合物 5 不会产生肝毒性。研究还调查了化合物 5 或纳曲酮对硫代苯甲酰胺肝毒性的影响。纳曲酮会加剧硫代苯甲酰胺介导的肝毒性，而化合物 5 则具有保肝作用。根据化合物 5 的理化性质，研究人员在大鼠酒精自我给药动物模型中对该化合物进行了研究。化合物 5 对酒精依赖和非酒精依赖 P 型大鼠的乙醇自我给药抑制显示出非常强的效力（即 ED50 值估计为 4-5 μ g/kg）。在狂饮型 P-rat 动物模型中，化合物 5 对酒精自我给药的抑制 ED50 值估计为 8 μ g/kg。研究结果表明，化合物 5 是一种强效的类药物 κ - 阿片受体拮抗剂，可用于戒酒药物的开发。
• SUBSTITUTED ARYLOXYPROPYLAMINES WITH SEROTONINERGIC AND/OR NOREPINEPHRINERGIC ACTIVITY
  申请人：Gant G. Thomas

  公开号：US20070155820A1

  公开（公告）日：2007-07-05

  Chemical syntheses and medical uses of novel inhibitors of the uptake of monoamine neurotransmitters and pharmaceutically acceptable salts and prodrugs thereof, for the treatment and/or management of psychotropic disorders, anxiety disorder, generalized anxiety disorder, depression, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, hot flashes, senile dementia, migraine, hepatopulmonary syndrome, chronic pain, nociceptive pain, neuropathic pain, painful diabetic retinopathy, bipolar depression, obstructive sleep apnea, psychiatric disorders, premenstrual dysphoric disorder, social phobia, social anxiety disorder, urinary incontinence, anorexia, bulimia nervosa, obesity, ischemia, head injury, calcium overload in brain cells, drug dependence, and/or premature ejaculation are described.