(S)-1-(4-trichloroacetamidophenoxy)-3-(3,4-dichlorophenylethylamino)-2-propanol | 1060787-91-8

• 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: (S)-1-(4-trichloroacetamidophenoxy)-3-(3,4-dichlorophenylethylamino)-2-propanol
• 英文别名: 2,2,2-trichloro-N-[4-[(2S)-3-[2-(3,4-dichlorophenyl)ethylamino]-2-hydroxypropoxy]phenyl]acetamide
• CAS: 1060787-91-8
• 化学式: C₁₉H₁₉Cl₅N₂O₃
• 分子量: 500.636
• InChiKey: UGUJDVLOQFWGMK-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  70.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-1-(4-trichloroacetamidophenoxy)-3-(3,4-dichlorophenylethylamino)-2-propanol 在 盐酸 作用下， 以 乙醇 为溶剂， 生成 (S)-1-(4-trichloroacetamidophenoxy)-3-(3,4-dichlorophenylethylamino)-2-propanol hydrochloride
  参考文献：
  名称：

  Enantiomeric Propanolamines as selective N-Methyl-d-aspartate 2B Receptor Antagonists

  摘要：

  Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors with IC50 values between 30-100 nM. Potency is strongly controlled by substitution on both rings and the centrally located amine nitrogen. SAR analysis suggests that well-balanced polarity and chain-length factors provide the greatest inhibitory potency. Structural comparisons based on 3D shape analysis and electrostatic complementarity support this conclusion. The antagonists are neuroprotective in both in vitro and in vivo models of ischemic cell death. In addition, some compounds exhibit anticonvulsant properties. Unlike earlier generation NMDA receptor antagonists and some NR2B-selective antagonists, the present series of propanolamines does not cause increased locomotion in rodents. Thus, the NR2B-selective antagonists exhibit a range of therapeutically interesting properties.

  DOI：

  10.1021/jm8002153
• 作为产物：
  描述：

  (S)-glycidyl N-trichloroacetamidophenyl ether 、 3,4-二氯苯乙胺 以 乙醇 为溶剂， 以78%的产率得到(S)-1-(4-trichloroacetamidophenoxy)-3-(3,4-dichlorophenylethylamino)-2-propanol
  参考文献：
  名称：

  Enantiomeric Propanolamines as selective N-Methyl-d-aspartate 2B Receptor Antagonists

  摘要：

  Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors with IC50 values between 30-100 nM. Potency is strongly controlled by substitution on both rings and the centrally located amine nitrogen. SAR analysis suggests that well-balanced polarity and chain-length factors provide the greatest inhibitory potency. Structural comparisons based on 3D shape analysis and electrostatic complementarity support this conclusion. The antagonists are neuroprotective in both in vitro and in vivo models of ischemic cell death. In addition, some compounds exhibit anticonvulsant properties. Unlike earlier generation NMDA receptor antagonists and some NR2B-selective antagonists, the present series of propanolamines does not cause increased locomotion in rodents. Thus, the NR2B-selective antagonists exhibit a range of therapeutically interesting properties.

  DOI：

  10.1021/jm8002153

文献信息

• NMDA Receptor Antagonists for Neuroprotection
  申请人：Liotta Dennis C.

  公开号：US20140031363A1

  公开（公告）日：2014-01-30

  Provided are compounds, pharmaceutical compositions and methods of treatment or prophylaxis of disorders associated with NMDA receptor activity, including neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds are of the general Formula I, or a pharmaceutically acceptable salt, ester, prodrug or derivative thereof are provided: wherein: each (L) k -Ar 1 is a substituted or unsubstituted, mono or bicyclic aryl or heteroaryl; W is a bond, alkyl, or alkenyl; X is a bond, NR 1 or O and each R 1 and R 2 is independently H, alkyl, alkenyl or aralkyl or R 1 and R 2 taken together form a 5-8 membered ring; R 3 -R 6 are selected from certain specific substituents or a carbonyl; Y is a bond, O, S, SO, SO 2 , CH 2 , NH, N(alkyl), or NHC(═O); and Z is OH, NR 6 R 7 , NR 8 SO 2 (alkyl), NR 8 C(O)NR 6 R 7 , NR 8 C(O)O(alkyl), NR 8 -dihydrothiazole, or NR 8 -dihydroimidazole or wherein Z can fuse with Ar 2 to form selected heterocycles.

  本发明提供了与NMDA受体活性相关的疾病的化合物、药物组合物和治疗或预防方法，包括神经病性疼痛、中风、创伤性脑损伤、癫痫和相关的神经事件或神经退行性疾病。提供了一般式I的化合物或其药学上可接受的盐、酯、前药或衍生物：其中：每个（L）k-Ar1是取代或未取代的、单环或双环芳基或杂环芳基；W是键、烷基或烯基；X是键、NR1或O，每个R1和R2独立地是H、烷基、烯基或芳基烷基，或者R1和R2共同形成一个5-8成员环；R3-R6选择自某些特定的取代基或羰基；Y是键、O、S、SO、SO2、CH2、NH、N（烷基）或NHC（═O）；Z是OH、NR6R7、NR8SO2（烷基）、NR8C（O）NR6R7、NR8C（O）O（烷基）、NR8-二氢噻唑或NR8-二氢咪唑，或者Z可以与Ar2融合形成选择的杂环。
• US8420680B2
  申请人：——

  公开号：US8420680B2

  公开（公告）日：2013-04-16
• US9079852B2
  申请人：——

  公开号：US9079852B2

  公开（公告）日：2015-07-14
• [EN] NMDA RECEPTOR ANTAGONISTS FOR NEUROPROTECTION<br/>[FR] ANTAGONISTES DES RÉCEPTEURS NMDA POUR LA NEUROPROTECTION
  申请人：UNIV EMORY

  公开号：WO2009006437A1

  公开（公告）日：2009-01-08

  Provided are compounds, pharmaceutical compositions and methods of treatment or prophylaxis of disorders associated with NMDA receptor activity, including neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds are of the general Formula I, or a pharmaceutically acceptable salt, ester, prodrug or derivative thereof are provided: Formula I wherein: each (L)k-Ar1 is a substituted or unsubstituted, mono or bicyclic aryl or heteroaryl; W is a bond, alkyl, or alkenyl; X is a bond, NR1 or O and each R1 and R2 is independently H, alkyl, alkenyl or aralkyl or R1 and R2 taken together form a 5-8 membered ring; R3 R6 are selected from certain specific substituents or a carbonyl; Y is a bond, O, S, SO, SO2, CH2, NH, N(alkyl), or NHC(=0); and Z is OH, NR6R7, NR8SO2(alkyl), NR8C(O)NR6R7, NR8C(O)O(alkyl), NR8- dihydrothiazole, or NR8-dihydroimidazole or wherein Z can fuse with Ar2 to form selected heterocycles.
• [EN] NMDA RECEPTOR ANTAGONISTS FOR THE TREATMENT OF NEUROPSYCHIATRIC DISORDERS<br/>[FR] ANTAGONISTES DES RÉCEPTEURS NMDA UTILISABLES POUR LE TRAITEMENT DE TROUBLES NEUROPSYCHIATRIQUES
  申请人：UNIV EMORY

  公开号：WO2009137843A2

  公开（公告）日：2009-11-12

  Provided are pharmaceutical compositions and methods of treatment or prophylaxis of certain neuropsychiatric conditions, in particular mood disorders. The compounds are of the general Formula I-V as described herein.