methyl 3-cyano-2-trifluoromethanesulfonyloxy-1-naphthoate | 267663-95-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl 3-cyano-2-trifluoromethanesulfonyloxy-1-naphthoate
• 英文别名: methyl 3-Cyano-2-{[(trifluoromethyl)sulfonyl]oxy}-1-naphthoate；methyl 3-cyano-2-(trifluoromethylsulfonyloxy)naphthalene-1-carboxylate
• CAS: 267663-95-6
• 化学式: C₁₄H₈F₃NO₅S
• 分子量: 359.282
• InChiKey: UQWVXQCGGMZERW-UHFFFAOYSA-N

物化性质

• 沸点：
  492.0±45.0 °C(Predicted)
• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl 3-cyano-2-trifluoromethanesulfonyloxy-1-naphthoate 在 palladium on activated charcoal 四(三苯基膦)钯 、 草酰氯 、 碘代三甲硅烷 、 2,6-二叔丁基-4-甲基苯酚 、 氢气 、 N,N-二甲基甲酰胺 、 lithium chloride 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 为溶剂， 70.0~75.0 ℃ 、344.74 kPa 条件下， 反应 29.0h， 生成 3-Cyano-2-ethyl-1-naphthoyl chloride
  参考文献：
  名称：

  Structural Analysis and Optimization of NK₁ Receptor Antagonists through Modulation of Atropisomer Interconversion Properties

  摘要：

  We have previously described a series of antagonists that showed high potency and selectivity for the NK1 receptor. However, these compounds also had the undesirable property of existing as a mixture of interconverting rotational isomers. Here we show that alteration of the 2-naphthyl substituent can modulate the rate of isomer exchange. Comparisons of the NK1 receptor affinity for the various conformational. forms has facilitated the development of a detailed NK1 pharmacophore model.

  DOI：

  10.1021/jm030197g
• 作为产物：
  描述：

  2-甲氧基-3-氰基-1-萘酸甲酯 在 碘 、 magnesium 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 、 苯 为溶剂， 反应 1.5h， 生成 methyl 3-cyano-2-trifluoromethanesulfonyloxy-1-naphthoate
  参考文献：
  名称：

  Structural Analysis and Optimization of NK₁ Receptor Antagonists through Modulation of Atropisomer Interconversion Properties

  摘要：

  We have previously described a series of antagonists that showed high potency and selectivity for the NK1 receptor. However, these compounds also had the undesirable property of existing as a mixture of interconverting rotational isomers. Here we show that alteration of the 2-naphthyl substituent can modulate the rate of isomer exchange. Comparisons of the NK1 receptor affinity for the various conformational. forms has facilitated the development of a detailed NK1 pharmacophore model.

  DOI：

  10.1021/jm030197g

文献信息

• Neurokinin antagonists for use as medicaments
  申请人：——

  公开号：US20030158170A1

  公开（公告）日：2003-08-21

  A compound having the general formula (I) and methods of using such compounds for the treatment of diseases and pharmaceutical composition comprising such compounds.

  一种具有通式(I)的化合物，以及使用此类化合物治疗疾病的方法和包含此类化合物的制药组合物。
• [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。
• New neurokinin antagonists for use as medicaments
  申请人：Albert Scott Jeffrey

  公开号：US20070021406A1

  公开（公告）日：2007-01-25

  The present application relates to internally cyclized naphthamide compounds of the formula Ia (wherein R 1a , R 1b , R 1c , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X 1 , X 2 , Y, Z, and n are as defined herein), which are useful, for example, for antagonizing the pharmacological actions of the neurokinin 1 (NK 1 ) receptor. In particular, these compounds are useful in the treatment of diseases in which Substance P is involved such as, for example, major depressive disorder, severe anxiety disorders, stress disorders, major depressive disorder with anxiety, eating disorders, bipolar disorder, substance use disorder, schizophrenic disorders, psychotic disorders, movement disorders, cognitive disorders, depression and/or anxiety, mania or hypomania, aggressive behaviour, obesity, rheumatoid arthritis, Alzheimer's disease, cancer, oedema, allergic rhinitis, inflammation, pain, gastrointestinal-hypermotility, Huntington's disease, chronic obstructive pulmonary disorder (COPD), hypertension, migraine, bladder hypermotility, and urticaria.

  本申请涉及公式Ia的内环化萘酰胺化合物（其中R1a，R1b，R1c，R2，R3，R4，R5，R6，R7，R8，X1，X2，Y，Z和n的定义如本文所述），这些化合物可用于拮抗神经激肽1（NK1）受体的药理作用。特别地，这些化合物可用于治疗与物质P有关的疾病，例如重度抑郁障碍、严重焦虑障碍、应激障碍、伴有焦虑的重度抑郁障碍、进食障碍、躁狂障碍、物质使用障碍、精神分裂障碍、精神病性障碍、运动障碍、认知障碍、抑郁和/或焦虑、狂躁或亢进行为、肥胖症、类风湿性关节炎、阿尔茨海默病、癌症、水肿、过敏性鼻炎、炎症、疼痛、胃肠道高动力性、亨廷顿病、慢性阻塞性肺疾病（COPD）、高血压、偏头痛、膀胱高动力性和荨麻疹。
• Naphthalenecarboxamides as tachykinin receptor antagonists
  申请人：AstraZeneca AB

  公开号：EP1433783A2

  公开（公告）日：2004-06-30

  A compound having the formula (I) wherein R1 is oxo, -ORa, -OC(=O)Rb; or (A); R2 is H; or R1 is -ORc and R2 is -ORd; or R1 and R2 together form -O(CH2)mO-; R3 is H or alkyl; R4, R5 and R6 are independently selected from hydroxy, cyano, nitro, trifluoromethoxy, trifluoromethyl, alkylsulfonyl, halo, alkoxy, alkyl, cyanoalkyl, alkenyl, alkynyl, carboxy, alkoxy-carbonyl, carbamoyl, alkylcarbamoyl, di-alkylcarbamoyl, alkanoyl, alkanoylamino, aminosulfonyl, and substituted alkyl; or R4 and R5 together form -OCH2O- or -OC(CH3)2O-; R6 may additionally be hydrogen; R7 is substituted phenyl; R8 is selected from hydrogen, hydroxy, alkoxy, alkanoyloxy, alkanoyl, alkoxycarbonyl, alkanoylamino, alkyl, carbamoyl, alkylcarbamoyl, and bis(alkyl)carbamoyl; Ra is hydrogen or alkyl; Rb is alkyl, aryl or arylalkyl; Rc and Rd are independently selected from alkyl; m is 2, 3, or 4; and X1 and X2 are independently H or halogen, wherein at least one of X1 and X2 are halogen; 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.

  具有式 (I) 的化合物 其中 R1 是氧代、-ORa、-OC(=O)Rb；或 (A)； R2 是 H；或 R1 是-ORc，R2 是-ORd；或 R1 和 R2 共同形成-O(CH2)mO-； R3 是 H 或烷基；R4、R5 和 R6 独立选自羟基、氰基、硝基、三氟甲氧基、三氟甲基、烷基磺酰基、卤代、烷氧基、烷基、氰基烷基、烯基、炔基、羧基、烷氧基羰基、氨基甲酰基、烷基氨基甲酰基、二烷基氨基甲酰基、烷酰基、烷酰氨基、氨基磺酰基和取代烷基；或 R4 和 R5 共同形成 -OCH2O- 或 -OC(CH3)2O-；R6 还可以是氢；R7 是取代的苯基；R8 选自氢、羟基、烷氧基、烷酰氧基、烷酰基、烷氧羰基、烷酰氨基、烷基、氨基甲酰基、烷基氨基甲酰基和双(烷基)氨基甲酰基；Ra 是氢或烷基；Rb 是烷基、芳基或芳烷基；Rc 和 Rd 独立地选自烷基；m 是 2、3 或 4；以及 X1 和 X2 独立地是 H 或卤素，其中 X1 和 X2 中至少有一个是卤素；及其任何药学上可接受的盐，以及它们在治疗抑郁症、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、胃肠道过度运动、焦虑症、呃逆、亨廷顿氏病、包括抑郁症在内的精神病、高血压、偏头痛、膀胱过度运动或荨麻疹中的用途，以及制造这些化合物和含有这些化合物的药物组合物的方法。
• A New Approach to the Rapid Parallel Development of Four Neurokinin Antagonists. Part 5. Preparation of ZM374979 Cyanoacid and Selective Crystallisation of ZM374979 Atropisomers
  作者：Jeremy S. Parker、Neil A. Smith、Matthew J. Welham、William O. Moss

  DOI：10.1021/op030041q

  日期：2004.1.1

  ZM374979 cyanoacid was prepared from ZD4974 cyanoester by a selective Grignard reaction followed by selective ester hydrolysis. On conversion of ZM374979 cyanoacid to ZM374979 free base, atropisomerism was observed, necessitating the development of a process for the selective crystallisation of a single atropisomer.