N-(2,5-difluorobenzyl)-6-{[3-hydroxy-1-(4-methoxy-phenyl)propyl]amino}pyridazine-3-carboxamide | 1431839-31-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-(2,5-difluorobenzyl)-6-{[3-hydroxy-1-(4-methoxy-phenyl)propyl]amino}pyridazine-3-carboxamide
• 英文别名: N-[(2,5-difluorophenyl)methyl]-6-[[3-hydroxy-1-(4-methoxyphenyl)propyl]amino]pyridazine-3-carboxamide
• CAS: 1431839-31-4
• 化学式: C₂₂H₂₂F₂N₄O₃
• 分子量: 428.438
• InChiKey: APUVFFKBKUSCEN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  96.4
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-氨基-3-(对甲氧基苯基)-1-丙醇 、 6-chloro-N-[(2,5-difluorophenyl)methyl]pyridazine-3-carboxamide 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 48.0h， 生成 N-(2,5-difluorobenzyl)-6-{[3-hydroxy-1-(4-methoxy-phenyl)propyl]amino}pyridazine-3-carboxamide
  参考文献：
  名称：

  [EN] Pyridazine Derivatives Useful in Therapy
  [FR] DÉRIVÉS DE PYRIDAZINE UTILES EN THÉRAPIE

  摘要：

  本发明提供了式I的化合物，其中：R表示从苯基、杂环芳基、杂环基和C3-6环烷基中选择的环状基团；其中每个环状基团可选地被从1到3个取代基所取代，所述取代基包括卤素、C-6烷基（可选地取代为1-3个卤素原子）、苯基、C-6烷氧基（可选地取代为1-3个卤素原子）、氰基、杂环芳基1a和杂环基1a；并且每个环状基团可选地融合到苯环或含有1到3个杂原子（所选的杂原子为N、O和S）的5-或16元杂芳香基或杂环基中；当基团被取代时，取代可以发生在可选融合的环系统的任何地方；并且其中，杂环基和杂环基1a可以另外被取代为=O；X表示键或C-6烷基（可以是直链或支链）；R2表示H或C-6烷基；R3表示H或C-6烷基；Y表示键或C-6烷基（可以是直链或支链，并可选地被OH或CF3取代）；R4表示从苯基、杂环芳基4、杂环基4和C3-6环烷基中选择的环状基团；其中每个环状基团可选地被从1到3个取代基所取代，所述取代基包括卤素、C-6烷基（可选地取代为1-3个卤素原子）、苯基、C-6烷基（可选地取代为1-3个卤素原子）、氰基、杂环芳基4a和杂环基4a；并且每个环状基团可选地融合到苯环或含有1到3个杂原子（所选的杂原子为N、O和S）的5-或6元杂芳香基或杂环基中；当基团被取代时，取代可以发生在可选融合的环系统的任何地方；并且其中，杂环基4和杂环基4a可以另外被取代为=O；杂环芳基、杂环芳基1a、杂环芳基4和杂环芳基4a独立地表示包含1到3个杂原子（所选的杂原子为N、O和S）的5-或6元杂芳香基；杂环基、杂环基1a、杂环基4和杂环基4a独立地表示包含1到3个杂原子（所选的杂原子为N、O和S）的5-或6元杂环基；以及其药学上可接受的盐和溶剂。该化合物可用作制药用途，特别是用于治疗纤维化疾病、癌症和疼痛。

  公开号：

  WO2013061297A1

文献信息

• Substituted pyridazines for the treatment of pain
  申请人：INHIBITAXIN LIMITED

  公开号：US10016420B2

  公开（公告）日：2018-07-10

  The invention provides compounds of formula I, wherein: R1 represents a cyclic group selected from phenyl, heteroaryl1, heterocyclyl1 and C3-6 cycloalkyl; wherein each cyclic group is optionally substituted with from 1 to 3 substituents selected from halo, C1-6 alkyl optionally substituted with 1-3 halogen atoms, phenyl, C1-6 alkoxy optionally substituted with 1-3 halogen atoms, cyano, heteroaryl1a and heterocyclyl1a; and wherein each cyclic group is optionally fused to a benzene ring or a 5- or 6-membered heteroaromatic or heterocyclic ring each containing from 1 to 3 heteroatoms (selected from N, O and S); and when the group is substituted the substitution may occur anywhere on the optionally fused ring system as a whole; and wherein heterocyclyl1 and heterocyclyl1a may additionally be substituted with ═O; X represents a bond or C1-6 alkylene (which may be straight or branched); R2 represents H or C1-6 alkyl; R3 represents H or C1-6 alkyl; Y represents a bond or C1-6 alkylene (which may be straight or branched, and optionally substituted with OH or CF3); R4 represents a cyclic group selected from phenyl, heteroaryl4, heterocyclyl4 and C3-6 cycloalkyl; wherein each cyclic group is optionally substituted with from 1 to 3 substituents selected from halo, C1-6 alkyl optionally substituted with 1-3 halogen atoms, phenyl, C1-6 alkyl substituted with phenyl, C1-6 alkoxy optionally substituted with 1-3 halogen atoms, cyano, heteroaryl4a and heterocyclyl4a; and wherein each cyclic group is optionally fused to benzene ring or a 5- or 6-membered heteroaromatic or heterocyclic ring each containing from 1 to 3 heteroatoms (selected from N, O and S); and when the group is substituted the substitution may occur anywhere on the optionally fused ring system as a whole; and wherein heterocyclyl4 and heterocyclyl4a may additionally be substituted with ═O; heteroaryl1, heteroaryl1a, heteroaryl4 and heteroaryl4a independently represent a 5- or 6-membered heteroaryl group containing from 1 to 3 heteroatoms (selected from N, O and S); and heterocyclyl1, heterocyclyl1a, heterocyclyl4 and heterocyclyl4a independently represent a 5- or 6-membered heterocyclyl group containing from 1 to 3 heteroatoms (selected from N, O and S); and pharmaceutically acceptable salts and solvates thereof. The compounds are useful as pharmaceuticals, particularly in the treatment of fibrotic diseases, cancer and pain.

  本发明提供了式 I 的化合物、 其中 R1 代表选自苯基、杂芳基1 、杂环基1 和 C3-6 环烷基的环状基团； 其中每个环状基团任选被 1 至 3 个取代基取代，这些取代基选自卤、任选被 1 至 3 个卤素原子取代的 C1-6 烷基、苯基、任选被 1 至 3 个卤素原子取代的 C1-6 烷氧基、氰基、杂芳基1a 和杂环基1a； 其中每个环状基团可选择与苯环或 5 或 6 元杂芳环或杂环融合，每个环含有 1 至 3 个杂原子（选自 N、O 和 S）；当基团被取代时，取代可发生在整个可选择融合环系统的任何位置； 其中杂环烯1 和杂环烯1a 可另外被═O 取代； X代表键或C1-6亚烷基(可以是直链或支链) R2 代表 H 或 C1-6 烷基； R3 代表 H 或 C1-6 烷基； Y 代表键或 C1-6 亚烷基（可以是直链或支链，可选择被 OH 或 CF3 取代）； R4 代表选自苯基、杂芳基4 、杂环基4 和 C3-6 环烷基的环状基团； 其中每个环状基团任选被 1 至 3 个取代基取代，这些取代基选自卤、任选被 1-3 个卤素原子取代的 C1-6 烷基、苯基、被苯基取代的 C1-6 烷基、任选被 1-3 个卤素原子取代的 C1-6 烷氧基、氰基、杂芳基4a 和杂环基4a； 其中每个环状基团可选择与苯环或 5 或 6 元杂芳环或杂环融合，每个环含有 1 至 3 个杂原子（选自 N、O 和 S）；当基团被取代时，取代可发生在整个可选择融合环系统的任何位置； 其中杂环基 4 和杂环基 4a 可另外被═O 取代； 杂芳基1、杂芳基1a、杂芳基4和杂芳基4a独立地代表含有1至3个杂原子(选自N、O和S)的5或6元杂芳基；以及 杂环基 1、杂环基 1a、杂环基 4 和杂环基 4a 独立地代表含有 1 至 3 个杂原子（选自 N、O 和 S）的 5 或 6 元杂环基； 及其药学上可接受的盐和溶剂。 这些化合物可用作药物，特别是用于治疗纤维化疾病、癌症和疼痛。
• PYRIDAZINE DERIVATIVES USEFUL IN THERAPY
  申请人：Inhibitaxin Limited

  公开号：EP2771325B1

  公开（公告）日：2017-06-28
• US20140275100A1
  申请人：——

  公开号：US20140275100A1

  公开（公告）日：2014-09-18
• SUBSTITUTED PYRIDAZINES FOR THE TREATMENT OF PAIN
  申请人：INHIBITAXIN LIMITED

  公开号：US20160287584A1

  公开（公告）日：2016-10-06

  The invention provides compounds of formula I, wherein: R 1 represents a cyclic group selected from phenyl, heteroaryl 1 , heterocyclyl 1 and C 3-6 cycloalkyl; wherein each cyclic group is optionally substituted with from 1 to 3 substituents selected from halo, C 1-6 alkyl optionally substituted with 1-3 halogen atoms, phenyl, C 1-6 alkoxy optionally substituted with 1-3 halogen atoms, cyano, heteroaryl 1a and heterocyclyl 1a ; and wherein each cyclic group is optionally fused to a benzene ring or a 5- or 6-membered heteroaromatic or heterocyclic ring each containing from 1 to 3 heteroatoms (selected from N, O and S); and when the group is substituted the substitution may occur anywhere on the optionally fused ring system as a whole; and wherein heterocyclyl 1 and heterocyclyl 1a may additionally be substituted with ═O; X represents a bond or C 1-6 alkylene (which may be straight or branched); R 2 represents H or C 1-6 alkyl; R 3 represents H or C 1-6 alkyl; Y represents a bond or C 1-6 alkylene (which may be straight or branched, and optionally substituted with OH or CF 3 ); R 4 represents a cyclic group selected from phenyl, heteroaryl 4 , heterocyclyl 4 and C 3-6 cycloalkyl; wherein each cyclic group is optionally substituted with from 1 to 3 substituents selected from halo, C 1-6 alkyl optionally substituted with 1-3 halogen atoms, phenyl, C 1-6 alkyl substituted with phenyl, C 1-6 alkoxy optionally substituted with 1-3 halogen atoms, cyano, heteroaryl 4a and heterocyclyl 4a ; and wherein each cyclic group is optionally fused to benzene ring or a 5- or 6-membered heteroaromatic or heterocyclic ring each containing from 1 to 3 heteroatoms (selected from N, O and S); and when the group is substituted the substitution may occur anywhere on the optionally fused ring system as a whole; and wherein heterocyclyl 4 and heterocyclyl 4a may additionally be substituted with ═O; heteroaryl 1 , heteroaryl 1a , heteroaryl 4 and heteroaryl 4a independently represent a 5- or 6-membered heteroaryl group containing from 1 to 3 heteroatoms (selected from N, O and S); and heterocyclyl 1 , heterocyclyl 1a , heterocyclyl 4 and heterocyclyl 4a independently represent a 5- or 6-membered heterocyclyl group containing from 1 to 3 heteroatoms (selected from N, O and S); and pharmaceutically acceptable salts and solvates thereof. The compounds are useful as pharmaceuticals, particularly in the treatment of fibrotic diseases, cancer and pain.
• US9273011B2
  申请人：——

  公开号：US9273011B2

  公开（公告）日：2016-03-01