N-[2-(S)-(3,4-dichlorophenyl)-4-oxobutyl]-N-methyl-3-cyano-2-methoxy-1-naphthamide | 263387-99-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-[2-(S)-(3,4-dichlorophenyl)-4-oxobutyl]-N-methyl-3-cyano-2-methoxy-1-naphthamide
• 英文别名: N-[(S)-2-(3,4-dichlorophenyl)-4-oxobutyl]-N-methyl-2-methoxy-3-cyano-1-naphthamide；3-cyano-N-[(2S)-2-(3,4-dichlorophenyl)-4-oxobutyl]-2-methoxy-N-methylnaphthalene-1-carboxamide
• CAS: 263387-99-1
• 化学式: C₂₄H₂₀Cl₂N₂O₃
• 分子量: 455.34
• InChiKey: QDSLQEBZBNSMQU-QGZVFWFLSA-N

物化性质

• 沸点：
  678.0±55.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  70.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[2-(S)-(3,4-dichlorophenyl)-4-oxobutyl]-N-methyl-3-cyano-2-methoxy-1-naphthamide 在 苯胺 作用下， 生成 N-[(S)-2-(3,4-Dichlorophenyl)-4-(phenylamino)butyl]-N-methyl-2-methoxy-3-cyano-1-naphthamide
  参考文献：
  名称：

  N-(2-phenyl-4-amino-butyl)-1-naphthamides as neurokinin-1 receptor antagonists

  摘要：

  化合物的一般式为（I）：R1R2N—CH2CH2—CHAr1—CH2—NR3—CO—R4，其中：R1为氢，C1-6烷基，C2-6烯基，芳基，C1-6烷酰基，C1-6烷氧羰基或芳基羰基；这些基团中的任何一个可以选择性地被取代；R2为氢或C1-6烷基；或者R1或R2被结合形成一个可以选择性地被取代的吗啡环；Ar1为苯基，单取代或双取代为卤素；R3为氢或C1-6烷基；R4为可以选择性地被取代的萘-1-基；或其药学上可接受的盐。这些化合物拮抗内源性神经肽tachykinins的药理作用，特别是神经激肽1（NK1）受体。

  公开号：

  US06476077B1
• 作为产物：
  描述：

  2-甲氧基-3-氰基-1-萘酸甲酯 在 lithium hydroxide 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 N-[2-(S)-(3,4-dichlorophenyl)-4-oxobutyl]-N-methyl-3-cyano-2-methoxy-1-naphthamide
  参考文献：
  名称：

  Design, Synthesis, and SAR of Tachykinin Antagonists:  Modulation of Balance in NK₁/NK₂ Receptor Antagonist Activity

  摘要：

  Through optimization of compounds based on the dual NK1/NK2 antagonist ZD6021, it was found that alteration of two key regions could modulate the balance of NK1 and NK2 potency. Substitution of the 2-naphthalene position in analogues of ZD6021 resulted in increased NK1 potency and thus afforded NK1 preferential antagonists. Alterations of the piperidine region could then increase NK2 potency to restore dual NK1/NK2 selectivity. Through these efforts, three novel receptor antagonists from a single chemically related series were identified; two are dual NK1/NK2 antagonists, and the third is an NK1 preferential antagonist. In this paper, the factors affecting the balance of NK1 and NK2 selectivity in this series are discussed and the in vitro and in vivo properties of the novel antagonists are described.

  DOI：

  10.1021/jm020094i

文献信息

• [EN] NAPHTHALENECARBOXAMIDES AS TACHYKININ RECEPTOR ANTAGONISTS<br/>[FR] NAPHTALENE-CARBOXAMIDES UTILISES EN TANT QU'ANTAGONISTES DES RECEPTEURS DES TACHYKININES
  申请人：ZENECA LTD

  公开号：WO2000020389A1

  公开（公告）日：2000-04-13

  A compound having formula (I) wherein R1 is oxo, -ORa, -OC(=O)Rb; or (A); R2 is H; or R?1 is -ORc and R2 is -ORd; or R1 and R2¿ together form -O(CH¿2?)mO-; and any pharmaceutically-acceptable salt thereof along with their use in treating depression, anxiety, asthma, rheumatoid arthritis, Alzheimer's disease, cancer, schizophrenia, oedema, allergic rhinitis, inflammation, pain, gastrointestinal-hypermotility, anxiety, emesis, Huntington's disease, psychoses including depression, hypertension, migraine, bladder hypermotility, or urticaria, along with methods of making the compounds and pharmaceutical compositions containing the compounds.

  化合物式(I)的化合物，其中R1是氧代、-ORa、-OC（=O）Rb；或（A）；R2是H；或者R1是-ORc且R2是-ORd；或者R1和R2在一起形成-O（CH2）mO-；以及其任何药学上可接受的盐，用于治疗抑郁症、焦虑症、哮喘、类风湿性关节炎、阿尔茨海默病、癌症、精神分裂症、水肿、过敏性鼻炎、炎症、疼痛、胃肠过度运动、焦虑症、呕吐、亨廷顿病、包括抑郁症、高血压、偏头痛、膀胱过度运动或荨麻疹的方法，以及制备这些化合物和含有这些化合物的制药组合物。
• Compounds
  申请人：——

  公开号：US20040106610A1

  公开（公告）日：2004-06-03

  A compound having the general formula R 1 R 2 N—CH 2 CH 2 —CHAr 1 —CH 2 —NR 3 —CO—R 4 (I) and methods of using such compounds for the treatment of diseases and pharmaceutical composition comprising such compounds.

  一种具有通式R1R2N—CH2CH2—CHAr1—CH2—NR3—CO—R4（I）的化合物及使用该化合物治疗疾病的方法和包含该化合物的制药组合物。
• Neurokinin-1 receptor antagonists
  申请人：——

  公开号：US20030092713A1

  公开（公告）日：2003-05-15

  Compounds having the general formula R 1 R 2 N—CH 2 CH 2 —CHAr 1 —CH 2 —NR 3 —CO—R 4 (I) wherein R 1 , R 2 , R 3 , R 4 and Ar are as defined in the specification, methods of making such compounds, methods of using such compounds for the treatment of diseases and pharmaceutical compositions comprising such compounds.

  具有一般式R1R2N—CH2CH2—CHAr1—CH2—NR3—CO—R4(I)的化合物，其中R1，R2，R3，R4和Ar如规范中所定义，制备这种化合物的方法，使用这种化合物治疗疾病的方法以及包含这种化合物的制药组合物。
• Naphthalenecarboxamides as tachykinin receptor antagonists
  申请人：Astrazeneca AB

  公开号：US06500818B1

  公开（公告）日：2002-12-31

  Compounds having the following formula wherein L, M, R2, R3, R4, R5, R6, R7, X1 and X2 are as defined in the specification, pharmaceutically-acceptable salt thereof, useful for treating depression, anxiety, asthma, rheumatoid arthritis, Alzheimer's disease, cancer, schizophrenia, oedema, allergic rhinitis, inflammation, pain, gastrointestinal-hypermotility, emesis, Huntington's disease, psychoses, hypertension, migraine, bladder hypermotility, or urticaria, compositions including such compounds and processes for making such compounds.

  具有以下式子的化合物，其中L，M，R2，R3，R4，R5，R6，R7，X1和X2如规范中定义，其药学上可接受的盐，用于治疗抑郁症、焦虑症、哮喘、类风湿性关节炎、阿尔茨海默病、癌症、精神分裂症、水肿、过敏性鼻炎、炎症、疼痛、胃肠过度活动、呕吐、亨廷顿病、精神病、高血压、偏头痛、膀胱过度活动或荨麻疹，包括这种化合物的组合物和制造这种化合物的过程。
• A New Approach to the Rapid Parallel Development of Four Neurokinin Antagonists. Part 3. Assembly of Neurokinin Antagonists
  作者：Jeremy S. Parker、Sharon A. Bowden、Catherine R. Firkin、Jonathan D. Moseley、Paul M. Murray、Matthew J. Welham、Richard Wisedale、Maureen J. Young、William O. Moss

  DOI：10.1021/op020066+

  日期：2003.1.1

  Four neurokinin antagonists were assembled using a rapid parallel development approach. Research Department processes were scaled up if process safety and robustness were not compromised. Using this approach, 1 kg of each compound was rapidly delivered for clinical trials.