1-methyl-2,4-dioxo-3-[4-(5-thioxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-benzyl]-1,2,3,4-tetrahydro-thieno[2,3-d]pyrimidine-6-carboxylic acid 4-methoxy-benzylamide | 448967-07-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-methyl-2,4-dioxo-3-[4-(5-thioxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-benzyl]-1,2,3,4-tetrahydro-thieno[2,3-d]pyrimidine-6-carboxylic acid 4-methoxy-benzylamide
• 英文别名: N-[(4-methoxyphenyl)methyl]-1-methyl-2,4-dioxo-3-[[4-(5-sulfanylidene-2H-1,2,4-oxadiazol-3-yl)phenyl]methyl]thieno[2,3-d]pyrimidine-6-carboxamide
• CAS: 448967-07-5
• 化学式: C₂₅H₂₁N₅O₅S₂
• 分子量: 535.604
• InChiKey: OWWUZWBXKBJTDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  173
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-[4-(N-Hydroxycarbamimidoyl)-benzyl]-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-thieno[2,3-d]pyrimidine-6-carboxylic acid 4-methoxy-benzylamide 、 di(1H-imidazol-2-yl)methanethione 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 柠檬酸 以 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 4.0h， 以to give 1-methyl-2,4-dioxo-3-[4-(5-thioxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-benzyl]-1,2,3,4-tetrahydro-thieno[2,3-d]pyrimidine-6-carboxylic acid 4-methoxy-benzylamide (0.2511 g) as a tan powder的产率得到1-methyl-2,4-dioxo-3-[4-(5-thioxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-benzyl]-1,2,3,4-tetrahydro-thieno[2,3-d]pyrimidine-6-carboxylic acid 4-methoxy-benzylamide
  参考文献：
  名称：

  Fused pyrimidinone matrix metalloproteinase inhibitors

  摘要：

  选择性MMP-13抑制剂是式1的融合嘧啶酮或其药学上可接受的盐，其中：W与其连接的碳原子形成一个5元环二自由基2X为O、S、SO、SO2、NR5或CH2；3B为O或NR5；或A和B结合形成—C≡C—；R1、R4和R5为氢、烷基、烯基、炔基、(CH2)n芳基、(CH2)n环烷基、C1-C6烷酰基或(CH2)nheteroaryl；R2和R3为氢、烷基、烯基、炔基、CN、NO2、NR4R5、(CH2)n环烷基、(CH2)n芳基或(CH2)nheteroaryl；R2还可以是卤素；n为0到5的整数；当R4和R5与它们都连接的氮一起形成含碳原子的3-8元环时，该环可以选择性地含有O、S或N，且可能被取代或未取代；但是R1和R3不能同时选择自氢和C1-C6烷基。

  公开号：

  US20030004172A1

文献信息

• Fused pyrimidinone matrix metalloproteinase inhibitors
  申请人：——

  公开号：US20030004172A1

  公开（公告）日：2003-01-02

  Selective MMP-13 inhibitors are fused pyrimidinones of the formula 1 or a pharmaceutically acceptable salt thereof, wherein: W, together with the carbon atoms to which it is attached, form a 5-membered ring diradical 2 X is O, S, SO, SO 2 , NR 5 , or CH 2 ; 3 B is O or NR 5 ; or A and B are taken together to form —C≡C—; R 1 , R 4 , and R 5 are hydrogen, alkyl, alkenyl, alkynyl, (CH 2 ) n aryl, (CH 2 ) n cycloalkyl, C 1 -C 6 alkanoyl, or (CH 2 ) n heteroaryl; R 2 and R 3 are hydrogen, alkyl, alkenyl, alkynyl CN, NO 2 , NR 4 R 5 , (CH 2 ) n cycloalkyl, (CH 2 ) n aryl, or (CH 2 ) n heteroaryl; R 2 may further be halo; n is an integer of from 0 to 5; and R 4 and R 5 when taken together with a nitrogen to which they are both attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing O, S, or N, and substituted or unsubstituted; with the proviso that R 1 and R 3 are not both selected from hydrogen and C 1 -C 6 alkyl.

  选择性MMP-13抑制剂是具有以下结构的嘧啶酮类化合物或其药用盐： 其中： W与其连接的碳原子一起形成一个5元环二自由基； X为O、S、SO、SO2、NR5或CH2； B为O或NR5； 或A和B结合形成—C≡C—； R1、R4和R5为氢、烷基、烯基、炔基、(CH2)n芳基、(CH2)n环烷基、C1-C6烷酰基或(CH2)n杂环芳基； R2和R3为氢、烷基、烯基、炔基、CN、NO2、NR4R5、(CH2)n环烷基、(CH2)n芳基或(CH2)n杂环芳基；R2还可以是卤素； n为0到5的整数； R4和R5与它们都连接的氮一起形成含碳原子且可选择含有O、S或N的3-8元环，可以是取代或未取代的； 但要注意R1和R3不同时选择自氢和C1-C6烷基。
• Combination of an allosteric carboxylic inhibitor of matrix metalloproteinase-13 with celecoxib or valdecoxib
  申请人：——

  公开号：US20040019053A1

  公开（公告）日：2004-01-29

  This invention provides a combination, comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with celecoxib, or a pharmaceutically acceptable salt thereof, or valdecoxib, or a pharmaceutically acceptable salt thereof. This invention also provides a method of treating a disease that is responsive to inhibition of MMP-13 and cyclooxygenase-2, comprising administering to a patient suffering from such a disease the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with celecoxib, or a pharmaceutically acceptable salt thereof, or valdecoxib, or a pharmaceutically acceptable salt thereof. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with celecoxib, or a pharmaceutically acceptable salt thereof, or valdecoxib, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. The invention combination may also be further combined with other pharmaceutical agents depending on the disease being treated.

  该发明提供了一种组合物，包括MMP-13的变构羧酸抑制剂或其药用盐，与Celecoxib或其药用盐，或Valdecoxib或其药用盐。该发明还提供了一种治疗对MMP-13和环氧合酶-2抑制敏感的疾病的方法，包括向患有这种疾病的患者施用包括MMP-13的变构羧酸抑制剂或其药用盐，与Celecoxib或其药用盐，或Valdecoxib或其药用盐的组合物。该发明还提供了一种药物组合物，包括包括MMP-13的变构羧酸抑制剂或其药用盐，与Celecoxib或其药用盐，或Valdecoxib或其药用盐的组合物，以及药用载体、稀释剂或赋形剂。该发明组合物还可以根据所治疗的疾病进一步与其他药物代理结合。
• Combination of an allosteric carboxylic inhibitor of matrix metalloproteinase-13 with a selective inhibitor of cyclooxygenase-2 that is not celecoxib or valdecoxib
  申请人：——

  公开号：US20040019054A1

  公开（公告）日：2004-01-29

  This invention provides a combination, comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib. This invention also provides a method of treating a disease that is responsive to inhibition of MMP-13 and cyclooxygenase-2, comprising administering to a patient suffering from such a disease the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib, and a pharmaceutically acceptable carrier, diluent, or excipient. This invention also provides a combination comprising an NSAID, or a pharmaceutically acceptable salt thereof, and an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with an NSAID, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. This invention also provides a method of treating a disease that is responsive to inhibition of MMP-13 and cyclooxygenase-1 or cyclooxygenase-2, comprising administering to a patient suffering from such a disease the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with an NSAID, or a pharmaceutically acceptable salt thereof. The invention combinations may also be further combined with other pharmaceutical agents depending on the disease being treated.

  本发明提供一种组合物，包括MMP-13的变构羧酸抑制剂或其药用盐，以及COX-2的选择性抑制剂或其药用盐，但不包括司来昔布或瓦来昔布。本发明还提供一种治疗对MMP-13和环氧合酶-2抑制响应的疾病的方法，包括向患有该疾病的患者施用包括MMP-13的变构羧酸抑制剂或其药用盐，以及COX-2的选择性抑制剂或其药用盐的本发明组合物，但不包括司来昔布或瓦来昔布。本发明还提供一种药物组合物，包括MMP-13的变构羧酸抑制剂或其药用盐，以及COX-2的选择性抑制剂或其药用盐的本发明组合物，但不包括司来昔布或瓦来昔布，以及药用载体、稀释剂或赋形剂。本发明还提供一种组合物，包括NSAID或其药用盐，以及MMP-13的变构羧酸抑制剂或其药用盐。本发明还提供一种药物组合物，包括MMP-13的变构羧酸抑制剂或其药用盐，以及NSAID或其药用盐的本发明组合物，以及药用载体、稀释剂或赋形剂。本发明还提供一种治疗对MMP-13和环氧合酶-1或环氧合酶-2抑制响应的疾病的方法，包括向患有该疾病的患者施用包括MMP-13的变构羧酸抑制剂或其药用盐，以及NSAID或其药用盐的本发明组合物。根据所治疾病的不同，本发明组合物也可以与其他药物组合。
• THIENO[2,3-D]PYRIMIDINDIONE DERIVATIVES AS MATRIX METALLOPROTEINASE INHIBITORS
  申请人：Warner-Lambert Company LLC

  公开号：EP1370562A1

  公开（公告）日：2003-12-17
• PHARMACEUTICAL COMPOSITIONS COMPRISING AN ALLOSTERIC CARBOXYLIC INHIBITOR OF MATRIX METALLOPROTEINASE-13 AND A SELECTIVE INHIBITOR OF CYCLOOXYGENASE-2
  申请人：Warner-Lambert Company LLC

  公开号：EP1530475A2

  公开（公告）日：2005-05-18