2-(3-fluoro-phenyl)-6-methoxy-pyrazolo[1,5-b]pyridazine-3-carboxylic acid methyl ester | 221148-39-6

• 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-(3-fluoro-phenyl)-6-methoxy-pyrazolo[1,5-b]pyridazine-3-carboxylic acid methyl ester
• 英文别名: methyl 2-(3-fluorophenyl)-6-methoxypyrazolo[1,5-b]pyridazine-3-carboxylate
• CAS: 221148-39-6
• 化学式: C₁₅H₁₂FN₃O₃
• 分子量: 301.277
• InChiKey: MHRUMWCBGSARNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  65.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(3-fluoro-phenyl)-6-methoxy-pyrazolo[1,5-b]pyridazine-3-carboxylic acid methyl ester 在 sodium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 水 、 吡啶盐酸盐 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 2-(3-fluorophenyl)-7H-pyrazolo[1,5-b]pyridazin-6-one
  参考文献：
  名称：

  [EN] USE OF CYCLOOXYGENASE-2 INHIBITORS FOR THE TREATMENT OF DEPRESSIVE DISORDERS
  [FR] UTILISATION DES INHIBITEURS DE LA CYCLOOXYGENASE-2 DANS LE TRAITEMENT DES TROUBLES DEPRESSIFS

  摘要：

  公开号：

  WO2005048999A3
• 作为产物：
  描述：

  1-(2,2-dibromo-vinyl)-3-fluoro-benzene 在 正丁基锂 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 hexanes 、 乙腈 为溶剂， 反应 21.0h， 生成 2-(3-fluoro-phenyl)-6-methoxy-pyrazolo[1,5-b]pyridazine-3-carboxylic acid methyl ester
  参考文献：
  名称：

  [EN] USE OF CYCLOOXYGENASE-2 INHIBITORS FOR THE TREATMENT OF DEPRESSIVE DISORDERS
  [FR] UTILISATION DES INHIBITEURS DE LA CYCLOOXYGENASE-2 DANS LE TRAITEMENT DES TROUBLES DEPRESSIFS

  摘要：

  公开号：

  WO2005048999A3

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(CH2)nCO2C1-6烷基，O(CH2)nSC1-6烷基，(CH2)nNR4R5，(CH2)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(CH2)nCO2C1-6烷基，O(CH2)nSC1-6烷基，(CH2)nNR4R5或(CH2)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（CH2）nCO2C1-6烷基，O（CH2）nSC1-6烷基，（CH2）nNR4R5，（CH2）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（CH2）nCO2C1-6烷基，O（CH2）nSC1-6烷基，（CH2）nNR4R5或（CH2）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（CH2）nCO2C1-6烷基，O（CH2）nSC1-6烷基，（CH2）nNR4R5，（CH2）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（CH2）nCO2C1-6烷基，O（CH2）nSC1-6烷基，（CH2）nNR4R5或（CH2）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(CH2)nCO2C1-6烷基、O(CH2)nSC1-6烷基、(CH2)nNR4R5、(CH2)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(CH2)nCO2C1-6烷基、O(CH2)nSC1-6烷基、(CH2)nNR4R5或(CH2)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（CH2）nCO2C1-6烷基，O（CH2）nSC1-6烷基，（CH2）nNR4R5，（CH2）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（CH2）nCO2C1-6烷基，O（CH2）nSC1-6烷基，（CH2）nNR4R5或（CH2）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。