6-fluoro-3-methylisoquinolin-5-amine | 608515-64-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 6-fluoro-3-methylisoquinolin-5-amine
• 英文别名: 5-amino-6-fluoro-3-methylisoquinoline
• CAS: 608515-64-6
• 化学式: C₁₀H₉FN₂
• 分子量: 176.193
• InChiKey: JJQKJVZURBXDCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  38.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-fluoro-3-methylisoquinolin-5-amine 在 吡啶 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.17h， 生成 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1R,3R)-3-methyl-3-phenylcyclopentyl]urea
  参考文献：
  名称：

  TRPV1 Antagonists

  摘要：

  本文揭示了具有以下式（I）的化合物或药用可接受的盐、溶剂或其组合物，其中X1、X2、X3、X4、J、K、L、X5、X6、Rb、G2和m在规范中有定义。还披露了包含这些化合物的组合物以及使用这些化合物和组合物治疗疾病和疾病的方法。

  公开号：

  US20120245163A1
• 作为产物：
  描述：

  2-溴-4-氟苯甲醛 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide nitronium tetrafluoborate 、 氢气 、 三乙胺 作用下， 以 环丁砜 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~71.0 ℃ 、206.85 kPa 条件下， 反应 5.13h， 生成 6-fluoro-3-methylisoquinolin-5-amine
  参考文献：
  名称：

  TRPV1 Antagonists

  摘要：

  本文揭示了具有以下式（I）的化合物或药用可接受的盐、溶剂或其组合物，其中X1、X2、X3、X4、J、K、L、X5、X6、Rb、G2和m在规范中有定义。还披露了包含这些化合物的组合物以及使用这些化合物和组合物治疗疾病和疾病的方法。

  公开号：

  US20120245163A1

文献信息

• [EN] TRPV1 ANTAGONISTS<br/>[FR] ANTAGONISTES DE TRPV1
  申请人：ABBOTT LAB

  公开号：WO2010045401A1

  公开（公告）日：2010-04-22

  Disclosed herein are compounds of Formula (I), or pharmaceutically acceptable salts, solvates, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, R4, and m are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

  本文披露了式（I）的化合物，或其药用可接受的盐、溶剂化合物、前药、前药的盐或它们的组合，其中R1、R2、R3、R4和m在规范中有定义。还披露了包含这种化合物的组合物以及使用这种化合物和组合物治疗疾病和疾病的方法。
• [EN] AMINO-HETEROCYCLES AS VR-1 ANTAGONISTS FOR TREATING PAIN<br/>[FR] HETEROCYCLES AMINES EN TANT QU'ANTAGONISTES DU RECEPTEUR VANILLOIDE (VR-1) POUR LE TRAITEMENT DE LA DOULEUR
  申请人：MERCK SHARP & DOHME

  公开号：WO2004046133A1

  公开（公告）日：2004-06-03

  the present invention provides a compound of formula (I): wherein V represents NR5, O, S, SO or S(O)2; W and X each independently represent CH or N; Y represents N, CH or C-Ar2, with the proviso that at least one, but no more than two, of W, X and Y are N; Z represents CH or C-Ar2, with the proviso that when Y is N or CH then Z is C-Ar2, and with the further proviso that when Y is C-Ar2 then Z is CH; Ar1 represents a fused 9 or 10 membered heterobicyclic ring system containing one, two, three or four heteroatoms selected from nitrogen, oxygen and sulfur, wherein at least one of the rings in said ring system is aromatic; Ar2 represents an aromatic ring selected from phenyl, pyridyl, pyrimidinyl and pyridazinyl which is optionally fused and substituted; R1 represents halogen, hydroxy, oxo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, haloC1-6alkyl, hydroxyC1-6alkyl, C1-6alkoxy, haloC1-6alkoxy, hydroxyC1-6alkoxy, C3-7cycloalkyl, C3-7cycloalkoxy, C3-5cycloalkylC1-4alkyl, cyano, nitro, SR6, SOR6, SO2R6, COR6, NR3COR6, CONR3R4, NR3SO2R6, SO2NR3R4, -(CH2)mcarboxy, esterified -(CH2)mcarboxy or -(CH2)mNR3R4; R2 represents hydrogen, halogen, hydroxy, C1-6alkyl, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy, haloC1-6alkoxy, unsubstituted phenyl or phenyl substituted with one or two groups selected from halogen, C1-6alkyl, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy or haloC1-6alkoxy; R3 and R4 are each independently hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl or fluoroC1-6alkyl; or R3 and R4 and the nitrogen atom to which they are attached together form a heteroaliphatic ring of 4 to 7 ring atoms, optionally substituted by one or two groups selected from hydroxy or C1-4alkoxy, which ring may optionally contain as one of the said ring atoms an oxygen or a sulfur atom, S(O), S(O)2, or NR5; R5 represents hydrogen, C1-4alkyl, hydroxyC1-4alkyl or C1-4alkoxyC1-4alkyl; R6 represents hydrogen, C1-6alkyl, fluoroC1-6alkyl, C3-7cycloalkyl, unsubstituted phenyl, or phenyl substituted with one or two groups selected from halogen, C1-6alkyl, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy or haloC1-6alkoxy; m is either zero or an integer from 1 to 4; n is either zero or an integer from 1 to 3; or a pharmaceutically acceptable salt, N-oxide or a prodrug thereof; a pharmaceutical composition comprising it; its use in methods of treatment; use of it for the manufacture of a medicament for treating VR-1 related conditions such as those in which pain and/or inflammation predominate; and methods of treatment using it.

  本发明提供了一种具有以下结构的化合物（I）：其中V代表NR5、O、S、SO或S(O)2；W和X分别独立地代表CH或N；Y代表N、CH或C-Ar2，但至少有一个但不超过两个W、X和Y为N；Z代表CH或C-Ar2，但当Y为N或CH时，则Z为C-Ar2，并进一步规定当Y为C-Ar2时，Z为CH；Ar1代表包含一个、两个、三个或四个从氮、氧和硫中选择的杂原子的融合的9或10成员杂双环系统，其中所述环系中的至少一个环是芳香的；Ar2代表选择自苯基、吡啶基、嘧啶基和吡啶嗪基的芳香环，可以是可选地融合和取代的；R1代表卤素、羟基、氧、C1-6烷基、C2-6烯基、C2-6炔基、卤代C1-6烷基、羟基C1-6烷基、C1-6烷氧基、卤代C1-6烷氧基、羟基C1-6烷氧基、C3-7环烷基、C3-7环烷氧基、C3-5环烷基C1-4烷基、氰基、硝基、SR6、SOR6、SO2R6、COR6、NR3COR6、CONR3R4、NR3SO2R6、SO2NR3R4、-(CH2)m羧基、酯化的-(CH2)m羧基或-(CH2)mNR3R4；R2代表氢、卤素、羟基、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基、卤代C1-6烷氧基、未取代的苯基或苯基，其上取代有一个或两个从卤素、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基或卤代C1-6烷氧基中选择的基团；R3和R4各自独立地代表氢、C1-6烷基、C2-6烯基、C2-6炔基、C3-7环烷基或氟代C1-6烷基；或R3和R4和它们连接的氮原子共同形成一个由4到7个环原子组成的杂原烷环，可选地取代为一个或两个从羟基或C1-4烷氧基中选择的基团，该环可能可选地包含作为所述环原子之一的氧或硫原子、S(O)、S(O)2或NR5；R5代表氢、C1-4烷基、羟基C1-4烷基或C1-4烷氧基C1-4烷基；R6代表氢、C1-6烷基、氟代C1-6烷基、C3-7环烷基、未取代的苯基或苯基，其上取代有一个或两个从卤素、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基或卤代C1-6烷氧基中选择的基团；m为零或从1到4的整数；n为零或从1到3的整数；或其药学上可接受的盐、N-氧化物或前药；包含它的药物组合物；其在治疗方法中的用途；用于制造用于治疗VR-1相关病症的药物，例如疼痛和/或炎症占优势的病症的用途；以及使用它的治疗方法。
• Heteroaromatic urea derivatives as vr-1receptor modulators for treating pain
  申请人：Brown Elizabeth Rebecca

  公开号：US20050107388A1

  公开（公告）日：2005-05-19

  The present invention provides compounds of formula (I); pharmaceutically acceptable salts and N-oxides thereof in which A, B, D and E are C or N with the proviso that one or more are N, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are simple substituents, n is 0-3 and y is an aryl, heteroaryl, carbocyclyl or fused-carbocyclyl group; as VR-1 antagonists for treating conditions or diseases in which pain and/or inflammation predominates; the use of the same for manufacturing medicaments, pharmaceutical compositions comprising them and methods of treatment utilising them.

  本发明提供了式（I）的化合物；其药学上可接受的盐和N-氧化物，其中A，B，D和E是C或N，但其中一个或多个是N，R1，R2，R3，R4，R5和R6是简单的取代基，n是0-3，y是芳基，杂环芳基，碳环芳基或融合的碳环芳基基团；作为VR-1拮抗剂，用于治疗疼痛和/或炎症占优势的疾病或症状；同样的用于制造药物、包含它们的制剂和利用它们的治疗方法。
• Amino-heterocycles as vr-1 antagonists for treating pain
  申请人：Blurton Peter

  公开号：US20060040947A1

  公开（公告）日：2006-02-23

  the present invention provides a compound of formula (I): wherein V represents NR 5 , O, S, SO or S(O) 2 ; W and X each independently represent CH or N; Y represents N, CH or C—Ar 2 , with the proviso that at least one, but no more than two, of W, X and Y are N; Z represents CH or C—Ar 2 , with the proviso that when Y is N or CH then Z is C—Ar 2 , and with the further proviso that when Y is C—Ar 2 then Z is CH; Ar 1 represents a fused 9 or 10 membered heterobicyclic ring system containing one, two, three or four heteroatoms selected from nitrogen, oxygen and sulfur, wherein at least one of the rings in said ring system is aromatic; Ar 2 represents an aromatic ring selected from phenyl, pyridyl, pyrimidinyl and pyridazinyl which is optionally fused and substituted; R 1 represents halogen, hydroxy, oxo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, haloC 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 alkoxy, haloC 1-6 alkoxy, hydroxyC 1-6 alkoxy, C 3-7 cycloalkyl, C 3-7 cycloalkoxy, C 3-5 cycloalkylC 1-4 alkyl, cyano, nitro, SR 6 , SOR 6 , SO 2 R 6 , COR 6 , NR 3 COR 6 , CONR 3 R 4 , NR 3 SO 2 R 6 , SO 2 NR 3 R 4 , —(CH 2 ) m carboxy, esterified —(CH 2 ) m carboxy or —(CH 2 ) m NR 3 R 4 ; R 2 represents hydrogen, halogen, hydroxy, C 1-6 alkyl, haloC 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 alkoxy, haloC 1-6 alkoxy, unsubstituted phenyl or phenyl substituted with one or two groups selected from halogen, C 1-6 alkyl, haloC 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 alkoxy or haloC 1-6 alkoxy; R 3 and R 4 are each independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl or fluoroC 1-6 alkyl; or R 3 and R 4 and the nitrogen atom to which they are attached together form a heteroaliphatic ring of 4 to 7 ring atoms, optionally substituted by one or two groups selected from hydroxy or C 1-4 alkoxy, which ring may optionally contain as one of the said ring atoms an oxygen or a sulfur atom, S(O), S(O) 2 , or NR 5 ; R 5 represents hydrogen, C 1-4 alkyl, hydroxyC 1-4 alkyl or C 1-4 alkoxyC 1-4 alkyl; R 6 represents hydrogen, C 1-6 alkyl, fluoroC 1-6 alkyl, C 3-7 cycloalkyl, unsubstituted phenyl, or phenyl substituted with one or two groups selected from halogen, C 1-6 alkyl, haloC 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 alkoxy or haloC 1-6 alkoxy; m is either zero or an integer from 1 to 4; n is either zero or an integer from 1 to 3; or a pharmaceutically acceptable salt, N-oxide or a prodrug thereof; a pharmaceutical composition comprising it; its use in methods of treatment; use of it for the manufacture of a medicament for treating VR-1 related conditions such as those in which pain and/or inflammation predominate; and methods of treatment using it.

  本发明提供了一种化合物，其化学式为（I）：其中V代表NR5、O、S、SO或S（O）2；W和X各自独立地代表CH或N；Y代表N、CH或C-Ar2，但至少有一个，但不超过两个，W、X和Y是N；Z代表CH或C-Ar2，但当Y为N或CH时，Z为C-Ar2，且进一步规定当Y为C-Ar2时，Z为CH；Ar1代表一个融合的9或10个成员的杂双环环系统，其中包含从氮、氧和硫中选择的一个、两个、三个或四个杂原子，其中至少一个环为芳香环；Ar2代表一种芳香环，选择自苯基、吡啶基、嘧啶基和吡啶嗪基，可选地融合和取代；R1代表卤素、羟基、氧代、C1-6烷基、C2-6烯基、C2-6炔基、卤代C1-6烷基、羟基C1-6烷基、C1-6烷氧基、卤代C1-6烷氧基、羟基C1-6烷氧基、C3-7环烷基、C3-7环烷氧基、C3-5环烷基C1-4烷基、氰基、硝基、SR6、SOR6、SO2R6、COR6、NR3COR6、CONR3R4、NR3SO2R6、SO2NR3R4、-(CH2)m羧基、酯化的-(CH2)m羧基或-(CH2)mNR3R4；R2代表氢、卤素、羟基、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基、卤代C1-6烷氧基、未取代苯基或取代一个或两个群的苯基，所述群从卤素、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基或卤代C1-6烷氧基中选择；R3和R4各自独立地代表氢、C1-6烷基、C2-6烯基、C2-6炔基、C3-7环烷基或氟代C1-6烷基；或R3和R4及它们所连接的氮原子一起形成4至7个环原子的杂脂环，可选地取代一个或两个群，所述群从羟基或C1-4烷氧基中选择，该环可以选择地包含一个氧原子或硫原子、S（O）、S（O）2或NR5作为其中一个所述环原子；R5代表氢、C1-4烷基、羟基C1-4烷基或C1-4烷氧基C1-4烷基；R6代表氢、C1-6烷基、氟代C1-6烷基、C3-7环烷基、未取代苯基或取代一个或两个群的苯基，所述群从卤素、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基或卤代C1-6烷氧基中选择；m为零或1至4的整数；n为零或1至3的整数；或其药学上可接受的盐、N-氧化物或前药；包含它的制药组合物；它在治疗方法中的用途；用于制造治疗VR-1相关疾病的药物，例如疼痛和/或炎症占主导地位的疾病；以及使用它的治疗方法。
• Heteroaromatic urea derivatives as VR-1 receptor modulators for treating pain
  申请人：——

  公开号：US07285563B2

  公开（公告）日：2007-10-23

  The present invention provides compounds of formula (I); pharmaceutically acceptable salts and N-oxides thereof in which A, B, D and E are C or N with the proviso that one or more are N, R1, R2, R3, R4, R5 and R6 are simple substituents, n is 0-3 and y is an aryl, heteroaryl, carbocyclyl or fused-carbocyclyl group; as VR-1 antagonists for treating conditions or diseases in which pain and/or inflammation predominates; the use of the same for manufacturing medicaments, pharmaceutical compositions comprising them and methods of treatment utilizing them

  本发明提供了式(I)的化合物；其药学上可接受的盐和N-氧化物，其中A、B、D和E是C或N，但至少一个是N，R1、R2、R3、R4、R5和R6是简单的取代基，n为0-3，y是芳香基，杂环芳基，碳环基或融合碳环基；作为VR-1拮抗剂，用于治疗疼痛和/或炎症占优势的疾病或症状；将其用于制造药物，制备包含它们的制药组合物和利用它们的治疗方法。