methyl 3,4-dicyano-1-naphthoate | 255050-73-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl 3,4-dicyano-1-naphthoate
• 英文别名: methyl 3,4-dicyanonaphthalene-1-carboxylate
• CAS: 255050-73-8
• 化学式: C₁₄H₈N₂O₂
• 分子量: 236.23
• InChiKey: KSXBRXGWXKOFLJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  73.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3,4-dicyano-1-naphthoate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 3,4-dicyano-1-naphthoic acid
  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
• 作为产物：
  描述：

  methyl 3,4-dibromo-1-naphthoate 、 alkaline earth salt of/the/ methylsulfuric acid 在 吡啶 、 N-nethylpyrrolidinone 作用下， 反应 1.0h， 以26.6%的产率得到methyl 4-bromo-3-cyano-1-naphthoate
  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
• 作为试剂：
  描述：

  methyl 3,4-dibromo-1-naphthoate 、 氰化亚铜 、 吡啶 、 N-甲基吡咯烷酮 在 乙酸乙酯 、 ammonium hydroxide 、 碳酸氢钠 、 Sodium sulfate-III 、 正己烷 、 dichloromethane hexane 、 methyl 3,4-dicyano-1-naphthoate 作用下， 以 水 、 ammonium hydroxide 、 乙酸乙酯 为溶剂， 反应 1.0h， 以to afford methyl 3,4-dicyano-1-naphthoate (22 mg; 25%) [1H NMR (CDCl3) δ 9.01 (m, 1H), 8.41 (m, 1H), 8.36 (s, 1H), 7.9 (m, 2H), 4.08 (s, 3H); MS (EI) m/z 236 (M)], methyl 3-bromo-4-cyano-1-naphthoate (21.9 mg; 20.6%) [1H NMR (CDCl3) δ 8.86 (m, 1H), 8.31 (s, 1H), 8.28 (m, 1H). 7.75 (m, 2H), 4.05 (s, 3H); MS (EI) m/z 289 (M).], and methyl 4-bromo-3-cyano-1-naphthoate (28.3 mg; 26.6%) [1H NMR (CDCl3) δ 9.02 (m, 1H), 8.43 (m, 1H), 8.28 (s, 1H), 7.8 (m, 2H) 4.04 (s, 3H); MS (EI) m/z 289 (M)]的产率得到methyl 3,4-dicyano-1-naphthoate
  参考文献：
  名称：

  N-substituted naphthalene carboxamides as neurokinin-receptor antagonists

  摘要：

  化合物I的化学式为：其中R为烷基；R1为可选取代的苯基2-氧代四氢-1（2H）-嘧啶基，或2-氧代-1-哌啶基；R2为氢、烷氧基、烷酰氧基、烷氧羰基、烷酰胺基、酰基、烷基、氨基甲酰、N-烷基氨基甲酰、N,N-二烷基氨基甲酰（其中烷基可以相同或不同）、羟基、硫代酰基、硫代氨基甲酰、N-烷基硫代氨基甲酰或N,N-二烷基硫代氨基甲酰（其中烷基可以相同或不同）。X1和X2独立地为氢或卤素，但至少其中之一为卤素；R3、R4、R5和R6独立地为氢、氰基、硝基、三氟甲氧基、三氟甲基或烷基磺酰基，是至少一种速激肽受体的拮抗剂，可用于治疗抑郁症、焦虑症、哮喘、疼痛、炎症、尿失禁和其他疾病。描述了它们的制备过程，以及含有它们的组合物和它们的用途。

  公开号：

  US06365602B1

文献信息

• [EN] N-SUBSTITUTED NAPHTHALENE CARBOXAMIDES AS NEUROKININ-RECEPTOR ANTAGONISTS<br/>[FR] NAPHTALENE CARBOXAMIDES N-SUBSTITUES EN TANT QU'ANTAGONISTES DE RECEPTEURS DES NEUROKININES
  申请人：ZENECA LTD

  公开号：WO2000002859A1

  公开（公告）日：2000-01-20

  A compound of formula (I) wherein: R is alkyl; R1 is optionally substituted phenyl, 2-oxo-tetrahydro-1(2H)-pyrimidinyl, or 2-oxo-1-piperidinyl; R2 is hydrogen, alkoxy, alkanoyloxy, alkoxycarbonyl, alkanoylamino, acyl, alkyl, carbamoyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl where the alkyl groups are the same or different, hydroxy, thioacyl, thiocarbamoyl, N-alkylthiocarbamoyl, or N,N-dialkylthiocarbamoyl where the alkyl groups are the same or different. X¿1? and X2 are independently hydrogen or halo, provided that at least one of X1 or X2 is halo; and R?3, R4, R5, and R6¿ are independently hydrogen, cyano, nitro, trifluoromethoxy, trifluoromethyl, or alkylsulfonyl are antagonists of at least one tachykinin receptor and are useful in the treatment of depression, anxiety, asthma, pain, inflammation, urinary incontinence and other disease conditions. Processes for their preparation are described, as are compositions containing them and their use.

  化合物的化学式(I)，其中：R为烷基; R1为可选取代的苯基，2-氧代-四氢-1(2H)-嘧啶基或2-氧代-1-哌啶基; R2为氢、烷氧基、烷酰氧基、烷氧羰基、烷酰胺、烷基、氨基甲酰、N-烷基氨基甲酰、N,N-二烷基氨基甲酰，其中烷基团相同或不同，羟基、硫代酰基、硫代氨基、N-烷基硫代氨基、N,N-二烷基硫代氨基，其中烷基团相同或不同。X1和X2独立地为氢或卤素，但至少其中之一为卤素; R3、R4、R5和R6独立地为氢、氰基、硝基、三氟甲氧基、三氟甲基或烷基磺酰基，是至少一种快速激动肽受体的拮抗剂，可用于治疗抑郁症、焦虑症、哮喘、疼痛、炎症、尿失禁和其他疾病。描述了它们的制备过程，以及包含它们和它们的使用的组合物。
• N-SUBSTITUTED NAPHTHALENE CARBOXAMIDES AS NEUROKININ-RECEPTOR ANTAGONISTS
  申请人：AstraZeneca AB

  公开号：EP1097137A1

  公开（公告）日：2001-05-09
• US6365602B1
  申请人：——

  公开号：US6365602B1

  公开（公告）日：2002-04-02