N-(3,4-dichlorophenyl)-2-(2-(4-(methylsulfonamido)-phenoxy)ethylamino) acetamide | 1192367-01-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(3,4-dichlorophenyl)-2-(2-(4-(methylsulfonamido)-phenoxy)ethylamino) acetamide
• 英文别名: N-(3,4-dichlorophenyl)-2-[2-[4-(methanesulfonamido)phenoxy]ethylamino]acetamide
• CAS: 1192367-01-3
• 化学式: C₁₇H₁₉Cl₂N₃O₄S
• 分子量: 432.328
• InChiKey: HUACKZIZFZPSFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(3,4-dichlorophenyl)-2-(2-(4-(methylsulfonamido)-phenoxy)ethylamino) acetamide 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 以0.2 g的产率得到N-(3,4-dichlorophenyl)-2-(2-(4-(methylsulfonamido)-phenoxy)ethylamino) acetamide hydrochloride
  参考文献：
  名称：

  Synthesis, structural activity-relationships, and biological evaluation of novel amide-based allosteric binding site antagonists in NR1A/NR2B N-methyl-d-aspartate receptors☆

  摘要：

  The synthesis and structure-activity relationship analysis of a novel class of amide-based biaryl NR2B-selective NMDA receptor antagonists are presented. Some of the studied compounds are potent, selective, non-competitive, and voltage-independent antagonists of NR2B-containing NMDA receptors. Like the founding member of this class of antagonists (ifenprodil), several interesting compounds of the series bind to the amino terminal domain of the NR2B subunit to inhibit function. Analogue potency is modulated by linker length, flexibility, and hydrogen bonding opportunities. However, unlike previously described classes of NR2B-selective NMDA antagonists that exhibit off-target activity at a variety of monoamine receptors, the compounds described herein show much diminished effects against the hERG channel and alpha(1)-adrenergic receptors. Selections of the compounds discussed have acceptable half-lives in vivo and are predicted to permeate the blood-brain barrier. These data together suggest that masking charged atoms on the linker region of NR2B-selective antagonists can decrease undesirable side effects while still maintaining on-target potency. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2009.05.085
• 作为产物：
  描述：

  2-(4-氨基苯氧基)乙基氨基甲酸叔丁酯 在 盐酸 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 19.25h， 生成 N-(3,4-dichlorophenyl)-2-(2-(4-(methylsulfonamido)-phenoxy)ethylamino) acetamide
  参考文献：
  名称：

  Synthesis, structural activity-relationships, and biological evaluation of novel amide-based allosteric binding site antagonists in NR1A/NR2B N-methyl-d-aspartate receptors☆

  摘要：

  The synthesis and structure-activity relationship analysis of a novel class of amide-based biaryl NR2B-selective NMDA receptor antagonists are presented. Some of the studied compounds are potent, selective, non-competitive, and voltage-independent antagonists of NR2B-containing NMDA receptors. Like the founding member of this class of antagonists (ifenprodil), several interesting compounds of the series bind to the amino terminal domain of the NR2B subunit to inhibit function. Analogue potency is modulated by linker length, flexibility, and hydrogen bonding opportunities. However, unlike previously described classes of NR2B-selective NMDA antagonists that exhibit off-target activity at a variety of monoamine receptors, the compounds described herein show much diminished effects against the hERG channel and alpha(1)-adrenergic receptors. Selections of the compounds discussed have acceptable half-lives in vivo and are predicted to permeate the blood-brain barrier. These data together suggest that masking charged atoms on the linker region of NR2B-selective antagonists can decrease undesirable side effects while still maintaining on-target potency. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2009.05.085

文献信息

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

  公开号：US20090253710A1

  公开（公告）日：2009-10-08

  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: 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.

  提供了与NMDA受体活性相关的疾病治疗或预防的化合物、制药组合物和方法，包括神经病理性疼痛、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。提供了通式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是独立的H、烷基、烯基或芳基烷基，或R1和R2共同形成5-8成员环；R3-R6选自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Z可以与Ar2融合形成选择的杂环。
• NMDA Receptor Antagonists for the Treatment of Neuropsychiatric Disorders
  申请人：Dingledine Raymond J.

  公开号：US20110160223A1

  公开（公告）日：2011-06-30

  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.
• 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
• Synthesis, structural activity-relationships, and biological evaluation of novel amide-based allosteric binding site antagonists in NR1A/NR2B N-methyl-d-aspartate receptors☆
  作者：Cara A. Mosley、Scott J. Myers、Ernest E. Murray、Rose Santangelo、Yesim A. Tahirovic、Natalie Kurtkaya、Praseeda Mullasseril、Hongjie Yuan、Polina Lyuboslavsky、Phuong Le

  DOI：10.1016/j.bmc.2009.05.085

  日期：2009.9.1

  The synthesis and structure-activity relationship analysis of a novel class of amide-based biaryl NR2B-selective NMDA receptor antagonists are presented. Some of the studied compounds are potent, selective, non-competitive, and voltage-independent antagonists of NR2B-containing NMDA receptors. Like the founding member of this class of antagonists (ifenprodil), several interesting compounds of the series bind to the amino terminal domain of the NR2B subunit to inhibit function. Analogue potency is modulated by linker length, flexibility, and hydrogen bonding opportunities. However, unlike previously described classes of NR2B-selective NMDA antagonists that exhibit off-target activity at a variety of monoamine receptors, the compounds described herein show much diminished effects against the hERG channel and alpha(1)-adrenergic receptors. Selections of the compounds discussed have acceptable half-lives in vivo and are predicted to permeate the blood-brain barrier. These data together suggest that masking charged atoms on the linker region of NR2B-selective antagonists can decrease undesirable side effects while still maintaining on-target potency. (C) 2009 Published by Elsevier Ltd.