tert-butyl 6-fluoro-1-methyl-1H-indazol-4-ylcarbamate | 697739-08-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: tert-butyl 6-fluoro-1-methyl-1H-indazol-4-ylcarbamate
• 英文别名: tert-butyl N-(6-fluoro-1-methylindazol-4-yl)carbamate
• CAS: 697739-08-5
• 化学式: C₁₃H₁₆FN₃O₂
• 分子量: 265.287
• InChiKey: VDDRFUNTBYTEHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  56.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 6-fluoro-1-methyl-1H-indazol-4-ylcarbamate 在 盐酸 作用下， 以 甲醇 为溶剂， 以83%的产率得到6-氟-1-甲基-1H-吲唑-4-胺
  参考文献：
  名称：

  [EN] AMINO-HETEROCYCLES AS VR-1 ANTAGONISTS FOR TREATING PAIN
  [FR] HETEROCYCLES AMINES EN TANT QU'ANTAGONISTES DU RECEPTEUR VANILLOIDE (VR-1) POUR LE TRAITEMENT DE LA DOULEUR

  摘要：

  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。

  公开号：

  WO2004046133A1
• 作为产物：
  描述：

  6-Fluoro-4-isocyanato-1-methylindazole 、 叔丁醇 以 甲苯 为溶剂， 生成 tert-butyl 6-fluoro-1-methyl-1H-indazol-4-ylcarbamate
  参考文献：
  名称：

  [EN] DERIVATIVES OF N-(1H-INDAZOLYL)- AND N-(1H-INDOLYL)-UREA AS WELL AS RELATED COMPOUNDS AS MODULATORS OF THE VANILLOID-1 RECEPTOR (VR1) FOR THE TREATMENT OF PAIN
  [FR] UREES HETEROAROMATIQUES MODULANT LA FONCTION DU RECEPTEUR VANILLOIODE-1 (VR1)

  摘要：

  公开号：

  WO2005028445A3

文献信息

• [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。
• Derivatives of n-(1h-indazolyl)-and n-(1h-indolyl)-urea as well as related compounds as modulators of the vanilloid-1 receptor (vr1) for treatment of pain
  申请人：Fletcher Robert Stephen

  公开号：US20070078156A1

  公开（公告）日：2007-04-05

  Compounds of formula (I): wherein A, B and D are each C, N, O or S; E is C or N; the dotted circle within the five-membered ring indicates that the ring may be unsaturated or partially saturated; R 1 is halogen, hydroxy, C 1-6 alkyl, haloC 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, hydroxyC 1-6 alkoxy, C 3-7 cycloalkyl, C 3-5 cycloalkylC 1-4 alkyl, NR 7 R 8 , C 1-6 alkyl substituted with NR 7 R 8 , C, 1-6 alkoxy substituted with NR 7 R 8 , oxo, cyano, SO 2 NR 7 R 8 , CONR 7 R 8 , NHCOR 9 or NHSO 2 R 9 ; R 2 is halogen, hydroxy, C 1-6 alkyl, halo C 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, hydroxyC 1-6 alkoxy, C 3-7 cycloalkyl, C 3-5 cycloalkylC 1-4 alkyl, NR 7 R 8 , C 1-6 alkyl substituted with NR 7 R 8 , C 1-6 , alkoxy substituted with NR 7 R 8 , cyano, SON 2 R 7 R 8 , CONR 7 R 8 , NHCOR 9 , or NHSO 2 R 9 ; R 3 and R 4 are each independently hydrogen, C 1-6 , alkyl, phenyl or halophenyl; R 5 and R 6 are, at each occurrence, independently hydrogen, C 1-6 alkyl, phenyl, halophenyl or carboxy; X is an oxygen or sulfur atom; Y is an aryl, heteroaryl, carbocyclyl or fused-carbocyclyl group; n is either zero or an integer from 1 to 3; p is either zero or an integer from, 1 to 4; and q is either zero or an integer from 1 to 3; the other substituents are defined in claim 1; are useful as therapeutic compounds, particularly in the treatment of pain and other conditions ameliorated by the modulation of the function of the vanilloid-1 receptor (VR1).

  式(I)的化合物：其中A、B和D分别为C、N、O或S；E为C或N；五元环内的点圈表示该环可能不饱和或部分饱和；R1为卤素、羟基、C1-6烷基、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、C3-5环烷基C1-4烷基、NR7R8、C1-6烷基取代的NR7R8、C1-6烷氧基取代的NR7R8、氧代、氰基、SO2NR7R8、CONR7R8、NHCOR9或NHSO2R9；R2为卤素、羟基、C1-6烷基、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、C3-5环烷基C1-4烷基、NR7R8、C1-6烷基取代的NR7R8、C1-6烷氧基取代的NR7R8、氰基、SON2R7R8、CONR7R8、NHCOR9或NHSO2R9；R3和R4分别独立地为氢、C1-6烷基、苯基或卤代苯基；R5和R6在每次出现时独立地为氢、C1-6烷基、苯基、卤代苯基或羧基；X为氧或硫原子；Y为芳基、杂芳基、碳环基或融合碳环基基团；n为零或1至3的整数；p为零或1至4的整数；q为零或1至3的整数；其他取代基在权利要求中定义；在治疗疼痛和其他通过调节vanilloid-1受体（VR1）功能改善的疾病中特别有用的治疗化合物。
• DERIVATIVES OF N-(1H-INDAZOLYL)- AND N-(1H-INDOLYL)-UREA AS WELL AS RELATED COMPOUNDS AS MODULATORS OF THE VANILLOID-1 RECEPTOR (VR1) FOR THE TREATMENT OF PAIN
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP1675587A2

  公开（公告）日：2006-07-05
• [EN] HETEROAROMATIC UREAS WHICH MODULATE THE FUNCTION OF THE VANILLOID-1 RECEPTOR (VR1)<br/>[FR] UREES HETEROAROMATIQUES MODULANT LA FONCTION DU RECEPTEUR VANILLOIODE-1 (VR1)
  申请人：MERCK SHARP & DOHME

  公开号：WO2005028445A2

  公开（公告）日：2005-03-31

  Compounds of formula (I): wherein A, B and D are each C, N, O or S; E is C or N; the dotted circle within the five-membered ring indicates that the ring may be unsaturated or partially saturated;. R 1 is halogen, hydroxy, C 1-6 álkyl, haloC 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, hydroxyC 1-6 alkoxy, C 3-7 cycloalkyl, C 3-5 cycloalkylC 1-4 alkyl, NR7R8, C 1-6 alkyl substituted with NR7R8, C, 1-6 alkoxy substituted with NR7R8, oxo, cyano, SO2NR7R8, CONR7R8, NHCOR9 or NHSO2R 9 ; R2 is halogen, hydroxy, C 1-6 alkyl, halo C 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, hydroxyC 1-6 alkoxy, C 3-7 cycloalkyl, C 3-5 cycloalkylC 1-4 alkyl, NR7R8, C 1-6 alkyl substituted with NR7R8, C 1-6 , alkoxy substituted with NR7R8, cyano, SON2R7R8, CONR7R8, NHCOR9 , or NHSO2R9; R3 and R 4 are each independently hydrogen, C 1-6 ,alkyl, phenyl or halophenyl; R5 and R 6 are, at each occurrence, independently hydrogen, C 1-6 alkyl, phenyl, halophenyl or carboxy; X is an oxygen or sulfur atom; Y is an aryl, heteroaryl, carbocyclyl or fused-carbocyclyl group; n is either zero or an integer from 1 to 3; p is either zero or an integer from, 1 to 4; and q is either zero or an integer from 1 to 3; the other substituents are defined in claim 1; are useful as therapeutic compounds, particularly in the treatment of pain and other conditions ameliorated by the modulation of the function of the vanilloid-1 receptor (VR1).
• [EN] DERIVATIVES OF N-(1H-INDAZOLYL)- AND N-(1H-INDOLYL)-UREA AS WELL AS RELATED COMPOUNDS AS MODULATORS OF THE VANILLOID-1 RECEPTOR (VR1) FOR THE TREATMENT OF PAIN<br/>[FR] UREES HETEROAROMATIQUES MODULANT LA FONCTION DU RECEPTEUR VANILLOIODE-1 (VR1)
  申请人：MERCK SHARP & DOHME

  公开号：WO2005028445A3

  公开（公告）日：2005-06-02