2-(4-fluoro-phenyl)-6-methanesulfonyl-3-(4-methanesulfonyl-phenyl)-pyrazolo[1,5-b]pyridazine | 221148-47-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-fluoro-phenyl)-6-methanesulfonyl-3-(4-methanesulfonyl-phenyl)-pyrazolo[1,5-b]pyridazine
• 英文别名: 2-(4-fluorophenyl)-6-methylsulfonyl-3-(4-methylsulfonylphenyl)pyrazolo[1,5-b]pyridazine
• CAS: 221148-47-6
• 化学式: C₂₀H₁₆FN₃O₄S₂
• 分子量: 445.495
• InChiKey: XQLBZTCUEJYJOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  115
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-(4-氟苯基)-2-丙炔酸甲酯 在 sodium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 碳酸氢钠 、 sodium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙二醇二甲醚 、 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 2-(4-fluoro-phenyl)-6-methanesulfonyl-3-(4-methanesulfonyl-phenyl)-pyrazolo[1,5-b]pyridazine
  参考文献：
  名称：

  Identification of 2,3-diaryl-pyrazolo[1,5-b]pyridazines as potent and selective cyclooxygenase-2 inhibitors

  摘要：

  GW406381 (8), currently undergoing clinical evaluation for the treatment of inflammatory pain is a member of a novel series of 2,3-diaryl-pyrazolo[1,5-b]pyridazine based cyclooxygenase-2 (COX-2) inhibitors, which have been shown to be highly potent and selective. Several examples of the series, in addition to possessing favourable pharmacokinetic profiles and analgesic activity in vivo, have also demonstrated relatively high brain penetration in the rat compared with the clinically available compounds, which may ultimately prove beneficial in the treatment of pain. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.089

文献信息

• 2,3-Diaryl-pyrazolo[1,5-b]pyridazines derivatives, their preparation and their use as cyclooxygenase 2(COX-2) inhibitors
  申请人：Smithkline Beecham Corporation

  公开号：US06451794B1

  公开（公告）日：2002-09-17

  The invention provides the compounds of formula (I) and pharmaceutically acceptable derivatives thereof in which: R0 is halogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy substituted by one or more fluorine atoms, or O(CH2)nNR4R5; R1 and R2 are independently selected from H, C1-6alkyl, C1-6alkyl, substituted by one or more fluorine atoms, C1-6alkoxy, C1-6hydroxyalkyl, SC1-6alkyl, C(O)H, C(O)C1-6alkyl, C1-6alkylsulphonyl, C1-6alkoxy substituted by one or more fluorine atoms, O(CH2)nCO2C1-6alkyl, O(CH2)nSC1-6alkyl, (CH2)nNR4R5, (CH2)nSC1-6alkyl or C(O)NR4R5; with the proviso that when R0 is at the 4-position and is halogen, at least one of R1 and R2 is C1-6alkylsulphonyl, C1-6alkoxy substituted by one or more fluorine atoms, O(CH2)nCO2C1-6alkyl, O(CH2)nSC1-6alkyl, (CH2)nNR4R5 or (CH2)nSC1-6alkyl, C(O)NR4R5; R3 is C1-6alkyl or NH2; R4 and R5 are independently selected from H, or C1-6alkyl or, together with the nitrogen atom to which they are attached, form a 4-8 membered saturated ring; and n is 1-4. Compounds of formula (I) are potent and selective inhibitors of COX-2 and are of use in the treatment of the pain, fever, inflammation of a variety of conditions and diseases.

  该发明提供了式（I）的化合物及其在药学上可接受的衍生物，其中：R0为卤素，C1-6烷基，C1-6烷氧基，C1-6烷氧基上取代一个或多个氟原子，或O(CH2)nNR4R5；R1和R2分别选择自H，C1-6烷基，C1-6烷基，取代一个或多个氟原子，C1-6烷氧基，C1-6羟基烷基，SC1-6烷基，C(O)H，C(O)C1-6烷基，C1-6烷基磺酰基，C1-6烷氧基上取代一个或多个氟原子，O( )nCO2C1-6烷基，O( )nSC1-6烷基，( )nNR4R5，( )nSC1-6烷基或C(O)NR4R5；但当R0位于4位且为卤素时，R1和R2中至少一个为C1-6烷基磺酰基，C1-6烷氧基上取代一个或多个氟原子，O( )nCO2C1-6烷基，O( )nSC1-6烷基，( )nNR4R5或( )nSC1-6烷基，C(O)NR4R5；R3为C1-6烷基或NH2；R4和R5分别选择自H，或C1-6烷基，或与它们连接的氮原子一起形成4-8成员饱和环；n为1-4。式（I）的化合物是COX-2的有效且选择性抑制剂，并可用于治疗疼痛、发热、炎症等多种疾病和症状。
• [EN] 2,3-DIARYL-PYRAZOLO[1,5-B]PYRIDAZINES DERIVATIVES, THEIR PREPA RATION AND THEIR USE AS CYCLOOXYGENASE 2 (COX-2) INHIBITORS<br/>[FR] DERIVES DE 2,3-DIARYL-PYRAZOLO[1,5-B]PYRIDAZINE, LEUR PREPARATION ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE CYCLOOXYGENASE 2 (COX-2)
  申请人：GLAXO GROUP LIMITED

  公开号：WO1999012930A1

  公开（公告）日：1999-03-18

  (EN) The invention provides the compounds of formula (I) and pharmaceutically acceptable derivatives thereof in which: R0 is halogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy substituted by one or more fluorine atoms, or O(CH2)nNR4R5; R1 and R2 are independently selected from H, C1-6alkyl, C1-6alkyl, substituted by one or more fluorine atoms, C1-6alkoxy, C1-6hydroxyalkyl, SC1-6alkyl, C(O)H, C(O)C1-6alkyl, C1-6alkylsulphonyl, C1-6alkoxy substituted by one or more fluorine atoms, O(CH2)nCO2C1-6alkyl, O(CH2)nSC1-6alkyl, (CH2)nNR4R5, (CH2)nSC1-6alkyl or C(O)NR4R5; with the proviso that when R0 is at the 4-position and is halogen, at least one of R1 and R2 is C1-6alkylsulphonyl, C1-6alkoxy substituted by one or more fluorine atoms, O(CH2)nCO2C1-6alkyl, O(CH2)nSC1-6alkyl, (CH2)nNR4R5 or (CH2)nSC1-6alkyl, C(O)NR4R5; R3 is C1-6alkyl or NH2; R4 and R5 are independently selected from H, or C1-6alkyl or, together with the nitrogen atom to which they are attached, form a 4-8 membered saturated ring; and n is 1-4. Compounds of formula (I) are potent and selective inhibitors of COX-2 and are of use in the treatment of the pain, fever, inflammation of a variety of conditions and diseases.(FR) L'invention concerne les composés représentés par la formule (I) (I), ainsi que leurs sels acceptables sur le plan pharmaceutique, dans laquelle: R0 représente halogène, alkyle C1-C6, alkoxy C1-C6, alkoxy C1-C6 substitué par un ou plusieurs atomes de fluor, ou O(CH2)nNR4R5; R1 et R2 sont sélectionnés indépendamment dans H, alkyle C1-C6, alkyle C1-C6 substitué par un ou plusieurs atomes de fluor, alkoxy C1-C6, hydroxyalkyle C1-C6, alkyle SC1-C6, C(O)H, alkyle C(O)C1-C6, alkylsulfonyle C1-C6, alkoxy C1-C6 substitué par un ou plusieurs atomes de fluor, O(CH2)nCO2 alkyle C1-C6, O(CH2)nalkyle SC1-C6, (CH2)nNR4R5, (CH2)nalkyle SC1-C6, ou C(O)NR4R5; à condition que quand R0 est en position 4 et représente halogène, au moins un de R1 et de R2 représente alkylsulfonyle C1-C6, alkoxy C1-C6 substitué par un ou plusieurs atomes de fluor, O(CH2)nCO2alkyle C1-C6, O(CH2)n alkyle SC1-C6, (CH2)nNR4R5 ou (CH2)nalkyle SC1-C6, C(O)NR4R5; R3 représente alkyle C1-C6 ou NH2; R4 et R5 sont sélectionnés indépendamment dans H, ou alkyle C1-C6 et forment, avec l'atome d'azote auquel ils sont reliés, un noyau saturés à 4-8 éléments; et n est 1-4. Ces composés sont des inhibiteurs puissants et sélectifs de COX-2 et sont utiles pour traiter la douleur, la fièvre, l'inflammation dans une variété d'états et de maladies.

  该发明提供了式（I）化合物及其在药学上可接受的衍生物，其中：R0是卤素，C1-6烷基，C1-6烷氧基，C1-6烷氧基被一个或多个氟原子取代，或O（CH2）nNR4R5; R1和R2独立地选择自H，C1-6烷基，C1-6烷基，被一个或多个氟原子取代，C1-6烷氧基，C1-6羟基烷基，SC1-6烷基，C（O）H，C（O）C1-6烷基，C1-6烷基磺酰基，C1-6烷氧基被一个或多个氟原子取代，O（ ）nCO2C1-6烷基，O（ ）nSC1-6烷基，（ ）nNR4R5，（ ）nSC1-6烷基或C（O）NR4R5; 前提是当R0在4位且为卤素时，R1和R2中至少有一个是C1-6烷基磺酰基，C1-6烷氧基被一个或多个氟原子取代，O（ ）nCO2C1-6烷基，O（ ）nSC1-6烷基，（ ）nNR4R5或（ ）nSC1-6烷基，C（O）NR4R5; R3是C1-6烷基或NH2; R4和R5独立地选择自H，或C1-6烷基或与它们连接的氮原子一起形成4-8成员饱和环; n为1-4。式（I）化合物是COX-2的有效和选择性抑制剂，并可用于治疗各种疾病的疼痛，发热，炎症。
• 2,3-Diaryl-pyrazolo[1,5-B]pyridazines derivatives, their preparation and their use as cyclooxygenase 2 (COX-2) inhibitors
  申请人：——

  公开号：US20030008872A1

  公开（公告）日：2003-01-09

  The invention provides the compounds of formula (I) 1 and pharmaceutically acceptable derivatives thereof in which: R 0 is halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy substituted by one or more fluorine atoms, or O(CH 2 ) n NR 4 R 5 ; R 1 and R 2 are independently selected from H, C 1-6 alkyl, C 1-6 alkyl substituted by one or more fluorine atoms, C 1-6 alkoxy, C 1-6 hydroxyalkyl, SC 1-6 alkyl, C(O)H, C(O)C 1-6 alkyl, C 1-6 alkylsulphonyl, C 1-6 alkoxy substituted by one or more fluorine atoms, O(CH 2 ) n CO 2 C 1-6 alkyl, O(CH 2 ) n SC 1-6 alkyl, (CH 2 ) n NR 4 R 5 , (CH 2 ) n SC 1-6 alkyl or C(O)NR 4 R 5 ; with the proviso that when R 0 is at the 4-position and is halogen, at least one of R 1 and R 2 is C 1-6 alkylsulphonyl, C 1-6 alkoxy substituted by one or more fluorine atoms, O(CH 2 ) n CO 2 C 1-6 alkyl, O(CH 2 ) n SC 1-6 alkyl, (CH 2 ) n NR 4 R 5 or (CH 2 ) n SC 1-6 alkyl, C(O)NR 4 R 5 ; R 3 is C 1-6 alkyl or NH 2 ; R 4 and R 5 are independently selected from H, or C 1-6 alkyl or, together with the nitrogen atom to which they are attached, form a 4-8 membered saturated ring; and n is 1-4. Compounds of formula (I) are potent and selective inhibitors of COX-2 and are of use in the treatment of the pain, fever, inflammation of a variety of conditions and diseases.

  本发明提供了公式（I）1的化合物及其药学上可接受的衍生物，其中：R0是卤素，C1-6烷基，C1-6烷氧基，C1-6烷氧基被一个或多个氟原子取代，或O（CH2）nNR4R5；R1和R2分别选自H，C1-6烷基，C1-6烷基被一个或多个氟原子取代，C1-6烷氧基，C1-6羟基烷基，SC1-6烷基，C（O）H，C（O）C1-6烷基，C1-6烷基磺酰基，C1-6烷氧基被一个或多个氟原子取代，O（ ）nCO2C1-6烷基，O（ ）nSC1-6烷基，（ ）nNR4R5，（ ）nSC1-6烷基或C（O）NR4R5；但当R0位于4位且为卤素时，R1和R2中至少有一个为C1-6烷基磺酰基，C1-6烷氧基被一个或多个氟原子取代，O（ ）nCO2C1-6烷基，O（ ）nSC1-6烷基，（ ）nNR4R5或（ ）nSC1-6烷基，C（O）NR4R5；R3是C1-6烷基或NH2；R4和R5分别选自H，或C1-6烷基，或与它们所连接的氮原子一起形成一个4-8环饱和环；n为1-4。公式（I）的化合物是COX-2的有效和选择性抑制剂，并可用于治疗各种疾病的疼痛、发热、炎症。
• 2,3-diaryl-pyrazolo[1,5-b]pyridazines derivatives, their preparation and their use as cyclooxygenase, 2 (COX-2) inhibitors
  申请人：Beswick John Paul

  公开号：US20050113377A1

  公开（公告）日：2005-05-26

  The invention provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt, solvate, ester or salt or solvate of such ester, of a compound of formula (I) in which: R 0 is halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy substituted by one or more fluorine atoms, or O(CH 2 ) n NR 4 R 5 ; R 1 and R 2 are independently selected from H, C 1-6 alkyl, C 1-6 alkyl substituted by one or more fluorine atoms, C 1-6 alkoxy, C 1-6 hydroxyalkyl, SC 1-6 alkyl, C(O)H, C(O)C 1-6 alkyl, C 1-6 alkylsulphonyl, C 1-6 alkoxy substituted by one or more fluorine atoms, O(CH 2 ) n CO 2 C 1-6 alkyl, O(CH 2 ) n SC 1-6 alkyl, (CH 2 ) n NR 4 R 5 , (CH 2 ) n SC 1-6 alkyl or C(O)NR 4 R 5 ; with the proviso that when R 0 is at the 4-position and is halogen, at least one of R 1 and R 2 is C 1-6 alkylsulphonyl, C 1-6 alkoxy substituted by one or more fluorine atoms, O(CH 2 ) n CO 2 C 1-6 alkyl, O(CH 2 ) n SC 1-6 alkyl, (CH 2 ) n NR 4 R 5 or (CH 2 ) n SC 1-6 alkyl, C(O)NR 4 R 5 ; R 3 is C 1-6 alkyl or NH 2 ; R 4 and R 5 are independently selected from H and C 1-6 alkyl or, together with the nitrogen atom to which they are attached, form a 4-8 membered saturated ring; and n is 1-4; and an inhibitor of the release, or action, of tumour necrosis factor α.

  本发明提供了一种药物组合物，包括式(I)化合物或其药学上可接受的盐、溶剂化物、酯或其盐或酯的溶剂化物，其中：R0是卤素、C1-6烷基、C1-6烷氧基、经一或多个氟原子取代的C1-6烷氧基，或O(CH2)nNR4R5；R1和R2独立地选自H、C1-6烷基、经一或多个氟原子取代的C1-6烷基、C1-6烷氧基、C1-6羟基烷基、SC1-6烷基、C(O)H、C(O)C1-6烷基、C1-6烷基磺酰基、经一或多个氟原子取代的C1-6烷氧基、O( )nCO2C1-6烷基、O( )nSC1-6烷基、( )nNR4R5、( )nSC1-6烷基或C(O)NR4R5；但是，当R0位于4位且为卤素时，R1和R2中至少有一个是C1-6烷基磺酰基、经一或多个氟原子取代的C1-6烷氧基、O( )nCO2C1-6烷基、O( )nSC1-6烷基、( )nNR4R5或( )nSC1-6烷基、C(O)NR4R5；R3是C1-6烷基或NH2；R4和R5独立地选自H和C1-6烷基，或与它们所连接的氮原子一起形成4-8环饱和环；n为1-4；以及肿瘤坏死因子α释放或作用的抑制剂。
• 2,3-Diaryl-pyrazolo[1,5-b]pyridazines derivatives, their preparation and their use as cyclooxygenase 2 (COX-2) inhibirors
  申请人：——

  公开号：US20030040517A1

  公开（公告）日：2003-02-27

  The invention provides the compounds of formula (I) 1 and pharmaceutically acceptable derivatives thereof in which: R 0 is halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy substituted by one or more fluorine atoms, or O(CH 2 ) n NR 4 R 5 ; R 1 and R 2 are independently selected from H, C 1-6 alkyl, C 1-6 alkyl substituted by one or more fluorine atoms, C 1-6 alkoxy, C 1-6 hydroxyalkyl, SC 1-6 alkyl, C(O)H, C(O)C 1-6 alkyl, C 1-6 alkylsulphonyl, C 1-6 alkoxy substituted by one or more fluorine atoms, O(CH 2 ) n CO 2 C 1-6 alkyl, O(CH 2 ) n SC 1-6 alkyl, (CH 2 ) n NR 4 R 5 , (CH 2 ) n SC 1-6 alkyl or C(O)NR 4 R 5 ; with the proviso that when R 0 is at the 4-position and is halogen, at least one of R 1 and R 2 is C 1-6 alkylsulphonyl, C 1-6 alkoxy substituted by one or more fluorine atoms, O(CH 2 ) n CO 2 C 1-6 alkyl, O(CH 2 ) n SC 1-6 alkyl, (CH 2 ) n NR 4 R 5 or (CH 2 ) n SC 1-6 alkyl, C(O)NR 4 R 5 ; R 3 is C 1-6 alkyl or NH 2 ; R 4 and R 5 are independently selected from H, or C 1-6 alkyl or, together with the nitrogen atom to which they are attached, form a 4-8 membered saturated ring; and n is 1-4. Compounds of formula (I) are potent and selective inhibitors of COX-2 and are of use in the treatment of the pain, fever, inflammation of a variety of conditions and diseases.

  本发明提供了式（I）1的化合物及其药学上可接受的衍生物，其中： R0为卤素，C1-6烷基，C1-6烷氧基，C1-6烷氧基被一个或多个氟原子取代，或O（CH2）nNR4R5； R1和R2分别选自H，C1-6烷基，C1-6烷基被一个或多个氟原子取代，C1-6烷氧基，C1-6羟基烷基，SC1-6烷基，C（O）H，C（O）C1-6烷基，C1-6烷基磺酰基，C1-6烷氧基被一个或多个氟原子取代，O（ ）nCO2C1-6烷基，O（ ）nSC1-6烷基，（ ）nNR4R5，（ ）nSC1-6烷基或C（O）NR4R5；但当R0位于4位且为卤素时，R1和R2中至少有一个为C1-6烷基磺酰基，C1-6烷氧基被一个或多个氟原子取代，O（ ）nCO2C1-6烷基，O（ ）nSC1-6烷基，（ ）nNR4R5或（ ）nSC1-6烷基，C（O）NR4R5； R3为C1-6烷基或NH2； R4和R5分别选自H或C1-6烷基，或与它们所连接的氮原子一起形成4-8个成员的饱和环；以及 n为1-4。 式（I）的化合物是COX-2的有效和选择性抑制剂，并可用于治疗各种疾病和病症的疼痛、发热、炎症。