3β-(4-chlorophenyl)-2β-(3-(4'-methylphenyl)isoxazol-5-yl)tropane | 236754-02-2

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: 3β-(4-chlorophenyl)-2β-(3-(4'-methylphenyl)isoxazol-5-yl)tropane
• 英文别名: RTI 336；RTI-336 free base；5-[(1R,2S,3S,5S)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octan-2-yl]-3-(4-methylphenyl)-1,2-oxazole
• CAS: 236754-02-2
• 化学式: C₂₄H₂₅ClN₂O
• 分子量: 392.928
• InChiKey: AUXUFNHAVGIVDC-IKJKNFHUSA-N

物化性质

• 沸点：
  532.6±50.0 °C(Predicted)
• 密度：
  1.183±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  29.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  以46的产率得到3β-(4-chlorophenyl)-2β-(3-(4'-methylphenyl)isoxazol-5-yl)tropane
  参考文献：
  名称：

  J. Med. Chem. 2004, 47, 296-302

  摘要：

  DOI：

文献信息

• Medical fluid, a method of treatment and use of the fluid
  申请人：XVIVO PERFUSION AB

  公开号：US10271540B2

  公开（公告）日：2019-04-30

  A medical fluid for a harvested organ, tissue or part thereof, for evaluation and/or preservation. The fluid includes cocaine or a stimulating analog thereof; noradrenaline; and/or adrenaline. In addition, the fluid includes an oncotic agent, such as dextran; hormones, such as thyroxin; triiodotyronine; cortisone, insulin; and electrolytes and optionally nutrients in substantially physiological concentrations in a physiologically acceptable medium. In addition, the medical fluid further includes albumin in a concentration not exceeding 5.0%, and an oxygen carrier, such as erythrocytes. Further components may be dopamine; hydrocortisone; methylprednisolone; and a vasopressor agent, such as desmopressin. The cocaine; adrenaline; and noradrenaline are present in concentrations of each about 0.010 μM to 0.100 μM, for example in a ratio of 1:1:1.

  一种用于评估和/或保存摘取的器官、组织或其部分的医用液。该液体包括可卡因或其刺激类似物、去甲肾上腺素和/或肾上腺素。此外，该药液还包括一种抗肿瘤剂，如右旋糖酐；激素，如甲状腺素；三碘酪氨酸；可的松、胰岛素；以及电解质和生理上可接受的介质中基本为生理浓度的营养物质。此外，医用流体还包括浓度不超过 5.0% 的白蛋白和氧载体，如红细胞。其他成分可以是多巴胺、氢化可的松、甲基强的松龙和血管加压剂，如去氨加压素。可卡因、肾上腺素和去甲肾上腺素的浓度各约为 0.010 μM 至 0.100 μM，例如比例为 1:1:1。
• Synthesis, Monoamine Transporter Binding Properties, and Behavioral Pharmacology of a Series of 3β-(Substituted phenyl)-2β-(3‘-substituted isoxazol-5-yl)tropanes
  作者：F. Ivy Carroll、Neil Pawlush、Michael J. Kuhar、Gerald T. Pollard、James L. Howard

  DOI：10.1021/jm030453p

  日期：2004.1.1

  Several 3beta-(substituted phenyl)-2beta-(3-substituted isoxazol- 5- yl)tropanes (3a-t) were evaluated for their ability to inhibit radioligand binding at the DAT, 5-HTT, and NET as well as in gross observation and locomotor activity in mice and in rats trained to discriminate cocaine. All compounds showed high affinity for the DAT. The IC50 values ranged from 0.5 to 26 nM. With the exception of 3e and 3f, which have no substituent on the 2beta-(1,2-isoxazole) ring, all compounds were selective for the DAT relative to the 5-HTT and NET. No compound showed death when dosed at 100 mg/kg; however, most compounds did show signs typical of dopamine activity. The ED50 values for 2beta-(1,2-isoxazoles) that caused locomotor stimulation ranged from 0.2 to 12.8 mg/kg. Most compounds showed slower on-set and longer duration of action relative to cocaine. Surprisingly, 3beta-(4-methylphenyl)-2beta-[3-(4'-chlorophenyl)isoxazol-5-yl]tropane (3p) and 3beta-(4-methylphenyl)-2beta-[3-(4'-methylphenyl)isoxazol-5-yl]tropane (3r) did not produce significant increases in locomotor activity. In the cocaine discrimination test, all analogues showed full or at least 50% generalization with the exception of 3p, which did not show generalization. Importantly, both the locomotor activity and the cocaine discrimination ED50 values were correlated with the DAT binding but not 5-HTT and NET binding. This provides further support for the dopamine hypothesis of cocaine abuse. High DAT affinity and selectivity, increased locomotor activity with slow onset and long duration of action, and generalization to cocaine shown by the 3beta-(substituted phenyl)-2beta-(3-substituted isoxazol-5-yl)tropanes are properties thought necessary for a pharmacotherapy for treating cocaine abuse.
• A MEDICAL FLUID, A METHOD OF TREATMENT AND USE OF THE FLUID
  申请人：XVIVO Perfusion AB

  公开号：EP2568805B1

  公开（公告）日：2019-05-01
• COMPOSITION COMPRISING NOR-ADRENALINE AND A NET INHIBITOR FOR ADMINISTERING TO A BRAIN-DEAD, HEART-BEATING POTENTIAL ORGAN DONOR
  申请人：Steen Stig

  公开号：US20110270215A1

  公开（公告）日：2011-11-03

  A composition, an infusion solution, a method for treatment, and a kit for intravascular administration for treatment of a brain-dead, heart-beating, respirated, potential organ donor. The composition has a non-adrenaline and NET inhibitor for noradrenaline. The NET inhibitor may be cocaine or an analogue thereof or a tricyclic antidepressant. The composition may in addition include adrenaline, hydrocortisone, thyroxin, insulin, triiodotyronine, dopamine, a vasopressor agent, such as desmopressin, and methylprednisolone. The ratio between the NET inhibitor and nor-adrenaline is about 1:1. The composition may be dissolved in pure water, Ringer's acetate solution or physiological sodium chloride solution. The composition is infused in such an amount as to maintain a mean arterial pressure of about 60 mmHg. The composition may be infused by a pump at a rate of about 1.7 ml/hour decreasing dose-dependent to about 0.4 ml/hour after 24 hours.
• COMPOSITION COMPRISING NOR-ADRENALINE AND AMPHETAMINE FOR ADMINISTERING TO A BRAIN-DEAD, HEART-BEATING POTENTIAL ORGAN DONOR
  申请人：Steen Stig

  公开号：US20110281794A1

  公开（公告）日：2011-11-17

  A composition, an infusion solution, a method for treatment, and a kit for intravascular administration for treatment of a brain-dead, heart-beating, respirated, potential organ donor. The composition includes a non-adrenaline and amphetamine or an amphetamine-like substance. The composition may in addition include adrenaline, hydrocortisone, thyroxin, insulin, triiodotyronine, dopamine, a vasopressor agent, such as desmopressin, and methylprednisolone. The composition may be dissolved in pure water, Ringer's acetate solution or physiological sodium chloride solution. The composition is infused in such an amount as to maintain a mean arterial pressure of about 60 mmHg.