3-cyano-2-methoxy-1-naphthoic acid | 263387-97-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-cyano-2-methoxy-1-naphthoic acid
• 英文别名: 3-cyano-2-methoxynaphthalene-1-carboxylic acid
• CAS: 263387-97-9
• 化学式: C₁₃H₉NO₃
• 分子量: 227.219
• InChiKey: RNJQXQYJXMLIAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  70.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-cyano-2-methoxy-1-naphthoic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-Methoxy-3-cyano-1-naphthoyl Chloride
  参考文献：
  名称：

  Naphtho[2,1-b][1,5] and [1,2-f][1,4]oxazocines as selective NK1 antagonists

  摘要：

  Previously we reported on the synthesis and properties of a series of highly potent piperidinyl 2-subsituted-3-cyano-1-naphthamide NK1 antagonists that includes 3 and 4. Here we report our efforts to alleviate a troublesome atropisomeric property of those derivatives by introduction of a tethering bridge that, in addition, could be used to lock the resulting cyclic derivatives in a purported NK1 pharmacophore conformation. Using 3 as a starting point, the naphtho[2, 1-b][1,5]oxazocine, 17, was found to contain the optimal ring tether size (8) for retaining NK1 activity, was more NK1 versus NK2 selective, and reduced the number of atropisomers from four to two. Cyclic derivatives 29 and 32, which exist as essentially single atropisomers in the purported pharmacophore conformation. were prepared in the closely related naphtho[1,2-f][1,4]oxazocine series as part of an effort to use mono methyl substitution of the tethering bridge as a conformation stabilizing factor. Both 29 and 32 were found to be less active as NK1 antogonists than the non-methylated parent 28 possibly due to methyl group destabilization of receptor interaction. We discuss the above findings in the context of a previously proposed NK1 pharmacophore model and present a further refinement of that model. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.03.015
• 作为产物：
  描述：

  2-甲氧基-3-氰基-1-萘酸甲酯 在 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 3-cyano-2-methoxy-1-naphthoic acid
  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

文献信息

• [EN] NAPHTHYL ETHER COMPOUNDS AND THEIR USE<br/>[FR] COMPOSES DE NAPHTYL ETHER ET LEUR UTILISATION
  申请人：ASTRAZENECA AB

  公开号：WO2004022539A1

  公开（公告）日：2004-03-18

  Compounds having the following structure wherein R1, R2, R3, R4, R5, R6, R7 m and n are as defined in the specification, in vivo-hydrolysable precursors thereof, pharmaceutically-acceptable salts thereof, the use in therapy and pharmaceutical compositions and methods of treatment using the same.

  具有以下结构的化合物，其中R1、R2、R3、R4、R5、R6、R7、m和n如规范中定义，其体内可水解的前体，其药用盐，以及在治疗中的使用、制药组合物和使用相同的治疗方法。
• [EN] NAPHTHAMIDE DERIVATIVES AND THEIR USE<br/>[FR] DERIVES DE NAPHTAMIDE ET LEUR UTILISATION
  申请人：ASTRAZENECA AB

  公开号：WO2004020411A1

  公开（公告）日：2004-03-11

  Compounds having the following structure wherein R1, R2, R3, R4, m and n are as defined in the specification, in vivo-hydrolysable precursors thereof, pharmaceutically-acceptable salts thereof, the use in therapy and pharmaceutical compositions and methods of treatment using the same.

  具有以下结构的化合物，其中R1、R2、R3、R4、m和n如规范中定义，其体内可水解的前体，其药用可接受的盐，以及在治疗中的使用、制药组合物和使用相同方法的治疗方法。
• [EN] PIPERIDINE AMINE COMPOUNDS AND THEIR USE<br/>[FR] COMPOSES D'AMINE PIPERIDINE ET LEUR UTILISATION
  申请人：ASTRAZENECA AB

  公开号：WO2004056771A1

  公开（公告）日：2004-07-08

  Compounds having the formula[Chemical formula should be inserted here. Please see paper copy] wherein R1, R2, R3, R6, R7 and Ar are as defined in the specification, in vivo-hydrolysable precursors thereof, pharmaceutically-acceptable salts thereof, the use in therapy and pharmaceutical compositions and methods of treatment using the same.

  具有化学式[化学式应在此处插入。请参阅纸质副本]的化合物，其中R1、R2、R3、R6、R7和Ar如规范中定义，其体内可水解的前体，其药用可接受的盐，以及在治疗中的使用和使用相同的药物组合物和治疗方法。
• Novel n-( 2-phenyl-3-aminopropyl)naphtamides
  申请人：——

  公开号：US20040014809A1

  公开（公告）日：2004-01-22

  A compound of the formula 1 wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X 1 and X 2 are as defined in the specification useful for the treatment of diseases in which action of the neurokinin 1 receptor is implicated, methods of using such compounds and pharmaceutical compositions comprising such compounds.

  一种化合物的公式如下，其中R1、R2、R3、R4、R5、R6、X1和X2如规范中定义，用于治疗神经激肽1受体作用所涉及的疾病，使用这种化合物的方法以及包含这种化合物的药物组合物。
• N-(2-phenyl-4-amino-butyl)-1-naphthamides as neurokinin-1 receptor antagonists
  申请人：Astrazeneca AB

  公开号：US06476077B1

  公开（公告）日：2002-11-05

  A compound having the general formula (I): R1R2N—CH2CH2—CHAr1—CH2—NR3—CO—R4 wherein: R1 is hydrogen, C1-6 alkyl, C2-6 alkenyl, aryl, C1-6 alkanoyl C1-6 alkoxycarbonyl or arylcarbonyl; any of such groups being optionally substituted; R2 is hydrogen or C1-6 alkyl; or R1 or R2 are joined to form an optionally substituted morpholino ring; Ar1 is phenyl mono- or di-substituted by halo; R3 is hydrogen or C1-6 alkyl; R4 is optionally substituted naphth-1-yl; or pharmaceutically acceptable salts thereof. These compounds antagonize the pharmacological actions of the endogenous neuropeptide tachykinins, particularly the neurokinin 1 (NK1) receptor.

  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。