4-[5-fluoro-2(-4-methylpiperazin-1-yl)thiazol-4-yl]benzoic acid | 1059549-52-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-[5-fluoro-2(-4-methylpiperazin-1-yl)thiazol-4-yl]benzoic acid
• 英文别名: 4-[5-Fluoro-2-(4-methyl-piperazin-1-yl)-thiazol-4-yl]-benzoic acid；4-[5-fluoro-2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]benzoic acid
• CAS: 1059549-52-8
• 化学式: C₁₅H₁₆FN₃O₂S
• 分子量: 321.375
• InChiKey: LJVWINDNWIUBPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[5-fluoro-2(-4-methylpiperazin-1-yl)thiazol-4-yl]benzoic acid 在 盐酸 作用下， 以 水 为溶剂， 以79%的产率得到4-(5-fluoro-2-(4-methylpiperazin-1-yl)thiazol-4-yl)benzoic acid dihydrochloride
  参考文献：
  名称：

  Cysteine Protease Inhibitors

  摘要：

  II式化合物：其中R2为亮氨酸、异亮氨酸、环己基甘氨酸、O-甲基苏氨酸、4-氟亮氨酸或3-甲氧基缬氨酸的侧链；R3为H、甲基或F；Rq为三氟甲基，Rq′为H或Rq和Rq′定义酮基；Q为p-(C1-C6烷基磺酰基)苯基-或一个可选择取代的4-(C1-C6烷基)哌嗪-1-基噻唑-4-基-部分，用于治疗由于卡托普斯底蛋白K的不当表达或激活而表现出的疾病，例如骨质疏松症、骨关节炎、类风湿性关节炎或骨转移。

  公开号：

  US20090023748A1
• 作为产物：
  描述：

  4-(5-fluoro-2-(4-methylpiperazin-1-yl)thiazol-4-yl)benzoic acid methyl ester 在 lithium hydroxide 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以100%的产率得到4-[5-fluoro-2(-4-methylpiperazin-1-yl)thiazol-4-yl]benzoic acid
  参考文献：
  名称：

  Cysteine Protease Inhibitors

  摘要：

  II式化合物：其中R2为亮氨酸、异亮氨酸、环己基甘氨酸、O-甲基苏氨酸、4-氟亮氨酸或3-甲氧基缬氨酸的侧链；R3为H、甲基或F；Rq为三氟甲基，Rq′为H或Rq和Rq′定义酮基；Q为p-(C1-C6烷基磺酰基)苯基-或一个可选择取代的4-(C1-C6烷基)哌嗪-1-基噻唑-4-基-部分，用于治疗由于卡托普斯底蛋白K的不当表达或激活而表现出的疾病，例如骨质疏松症、骨关节炎、类风湿性关节炎或骨转移。

  公开号：

  US20090023748A1

文献信息

• [EN] PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE PROTÉASES
  申请人：MEDIVIR AB

  公开号：WO2010034788A1

  公开（公告）日：2010-04-01

  Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem subsituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one Of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O-C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.

  公式II的化合物：其中R1和R2分别为H、F或CH3；或者R1形成乙炔键，R2为H或C3-C6环烷基，可选地被一个或两个从甲基、CF3、OMe或卤素中独立选择的取代基取代；R3为C1-C3烷基或C3-C6环烷基，两者可选地被一个或两个甲基和/或氟、三氟甲基或甲氧基取代，当R3为C3-C6环烷基时，它也可以选择地被氟原子取代；R4为甲基或氟；m为0、1或2；E为键，或噻唑基，可选地被甲基或氟取代；A1为CH或N，A2为CR6R7或NR6，至少其中一个为N；R6为H、C1-C4烷基、C1-C4卤代烷基、C1-C3烷氧基-C1-C3烷基，或当A2为C时，R6也可以是C1-C4烷氧基或F；R7为H、C1-C4烷基或F或其药学上可接受的盐、N-氧化物或水合物，在治疗由于cathepsin K的不恰当表达或活化而表征的疾病方面具有用途，例如骨质疏松症、骨关节炎、类风湿关节炎或骨转移。
• Cysteine protease inhibitors
  申请人：Medivir AB

  公开号：US07893067B2

  公开（公告）日：2011-02-22

  Compounds of the formula II: wherein R2 is the side chain of leucine, isoleucine, cyclohexylglycine, O-methyl threonine, 4-fluoroleucine or 3-methoxyvaline; R3 is H, methyl or F; Rq is trifluoromethyl and Rq′ is H or Rq and Rq′ define keto; Q is a p-(C1-C6alkylsulphonyl)phenyl- or an optionally substituted 4-(C1-C6alkyl)piperazin-1-yl-thiazol-4-yl- moiety have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.

  公式II的化合物：其中R2是亮氨酸、异亮氨酸、环己基甘氨酸、O-甲基苏氨酸、4-氟亮氨酸或3-甲氧基缬氨酸的侧链；R3是H、甲基或F；Rq是三氟甲基，Rq′是H或Rq，且Rq和Rq′定义为酮基；Q是p-(C1-C6烷基磺酰基)苯基-或可选取代的4-(C1-C6烷基)哌嗪-1-基噻唑-4-基基团，在治疗因过度表达或激活猫hepsin K而表现为骨质疏松症、骨关节炎、类风湿性关节炎或骨转移的疾病中具有用途。
• CYSTEINE PROTEASE INHIBITORS
  申请人：NILSSON Magnus

  公开号：US20110105524A1

  公开（公告）日：2011-05-05

  Compounds of the formula II: wherein R 2 is the side chain of leucine, isoleucine, cyclohexylglycine, O-methyl threonine, 4-fluoroleucine or 3-methoxyvaline; R 3 is H, methyl or F; Rq is trifluoromethyl and Rq′ is H or Rq and Rq′ define keto; Q is a p-(C 1 -C 6 alkylsulphonyl)phenyl- or an optionally substituted 4-(C 1 -C 6 alkyl)piperazin-1-yl-thiazol-4-yl-moiety have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.

  式II的化合物： 其中，R2是亮氨酸、异亮氨酸、环己基甘氨酸、O-甲基苏氨酸、4-氟亮氨酸或3-甲氧基缬氨酸的侧链；R3是H、甲基或F；Rq是三氟甲基，Rq'是H或Rq，且Rq'定义为酮基；Q是p-(C1-C6烷基磺酰)苯基或可选取代的4-(C1-C6烷基)哌嗪-1-基噻唑-4-基基团。 该化合物在治疗因过度表达或激活卡他普星K而表现出的疾病（如骨质疏松、骨关节炎、类风湿性关节炎或骨转移）方面具有应用价值。
• PROTEASE INHIBITORS
  申请人：ODÉN Lourdes Salvador

  公开号：US20120289519A1

  公开（公告）日：2012-11-15

  Compounds of the formula II: wherein R 1 and R 2 are independently H, F or CH 3 ; or R 1 forms an ethynyl bond and R 2 is H or optionally substituted C 3 -C 6 cycloalkyl; R 3 is (optionally substituted) C 1 -C 3 alkyl or C 3 -C 6 cycloalkyl; R 4 is methyl or fluoro; m is 0-2; E is optionally substituted thiazolyl; A 1 and A 2 together define an optionally substituted piperazine or piperidine ring have utility in the treatment of osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.

  公式II的化合物： 其中， R1和R2独立地为H、F或CH3；或者R1形成一个乙炔键，R2是H或者可选取代的C3-C6环烷基； R3是（可选取代的）C1-C3烷基或C3-C6环烷基； R4是甲基或氟代甲基； m为0-2； E是可选取代的噻唑基； A1和A2共同定义一个可选取代的哌嗪环或哌啶环。 该化合物在治疗骨质疏松症、骨关节炎、类风湿性关节炎或骨转移方面具有用途。
• Protease inhibitors
  申请人：Medivir AB

  公开号：US08242119B2

  公开（公告）日：2012-08-14

  Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.

  化合物II的式子： 其中，R1和R2独立地为H、F或CH3；或者R1形成一个乙炔键，R2为H或C3-C6环烷基，该环烷基可选地被一个或两个取代基独立地选择为甲基、CF3、OMe或卤素； R3为C1-C3烷基或C3-C6环烷基，其中任一种均可选地被一个或两个甲基和/或氟、三氟甲基或甲氧基取代，当R3为C3-C6环烷基时，它可以选择地被氟取代； R4为甲基或氟；m为0、1或2；E为键或噻唑基，该噻唑基可选地被甲基或氟取代； A1为CH或N，A2为CR6R7或NR6，其中至少一个为N；R6为H、C1-C4烷基、C1-C4卤代烷基、C1-C3烷基-O-C1-C3烷基，当A2为C时，R6也可以是C1-C4烷氧基或F；R7为H、C1-C4烷基或对于药学上可接受的盐、N-氧化物或其水合物，在治疗因cathepsin K不适当表达或激活所致的疾病方面具有用途，如骨质疏松症、骨关节炎、类风湿性关节炎或骨转移。