4-[6-(3,4-dimethoxy-benzylcarbamoyl)-1-methyl-2,4-dioxo-1,4-dihydro-2H-thieno[2,3-d]pyrimidin-3-ylmethyl]-benzoic acid tert-butyl ester | 448965-37-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[6-(3,4-dimethoxy-benzylcarbamoyl)-1-methyl-2,4-dioxo-1,4-dihydro-2H-thieno[2,3-d]pyrimidin-3-ylmethyl]-benzoic acid tert-butyl ester
• 英文别名: tert-butyl 4-[[6-[(3,4-dimethoxyphenyl)methylcarbamoyl]-1-methyl-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]methyl]benzoate
• CAS: 448965-37-5
• 化学式: C₂₉H₃₁N₃O₇S
• 分子量: 565.647
• InChiKey: GJICHFIQNXDZNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  143
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-[6-(3,4-dimethoxy-benzylcarbamoyl)-1-methyl-2,4-dioxo-1,4-dihydro-2H-thieno[2,3-d]pyrimidin-3-ylmethyl]-benzoic acid tert-butyl ester 在 ethyl acetate n-hexane 作用下， 以 三氟乙酸 为溶剂， 反应 0.5h， 以to yield 4-[6-(3,4-dimethoxy-benzylcarbamoyl)-1-methyl-2,4-dioxo-1,4-dihydro-2H-thieno[2,3-d]pyrimidin-3-ylmethyl]-benzoic acid as a white solid (65 mg, 73%)的产率得到4-[6-(3,4-dimethoxy-benzylcarbamoyl)-1-methyl-2,4-dioxo-1,4-dihydro-2H-thieno[2,3-d]pyrimidin-3-ylmethyl]-benzoic acid
  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
• 作为产物：
  描述：

  3-(4-Tert-butyoxycarbonyl-benzyl)-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-thieno[2,3-d]pyrimidine-6-carboxylic acid 、 、 三乙胺 、 3,4-二甲氧基苄胺 以 二氯甲烷 为溶剂， 反应 16.0h， 以to yield 4-[6-(3,4-dimethoxy-benzylcarbamoyl)-1-methyl-2,4-dioxo-1,4-dihydro-2H-thieno[2,3-d]pyrimidin-3-ylmethyl]-benzoic acid tert-butyl ester as a white solid (78%)的产率得到4-[6-(3,4-dimethoxy-benzylcarbamoyl)-1-methyl-2,4-dioxo-1,4-dihydro-2H-thieno[2,3-d]pyrimidin-3-ylmethyl]-benzoic acid tert-butyl ester
  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

• 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
• [EN] THIENO'2,3-D PYRIMIDINDIONE DERIVATIVES AS MATRIX METALLOPROTEINASE INHIBITORS<br/>[FR] DERIVES DE THIENO'2,3-D PYRIMIDINONE UTILISES COMME INHIBITEURS DE METALLOPROTEINASES MATRICIELLES
  申请人：WARNER LAMBERT CO

  公开号：WO2002064598A1

  公开（公告）日：2002-08-22

  Selective MMP-13 inhibitors are fused pyrimidinones of the formula or a pharmaceutically acceptable salt thereof, wherein: W, together with the carbon atoms to which it is attached, form a 5-membered ring diradical Y is O, S, SO, SO2, NR5, or CH¿2, ?A is-C-or S-; B is O or NR?5¿; or A and B are taken together to form -C C-; R?1, R4, and R5¿ are hydrogen, alkyl, alkenyl, alkynyl, (CH¿2?)n aryl, (CH2)n cycloalkyl, C1 C6 alkanoyl, or (CH2)n heteroaryl; R?2 and R3¿ are hydrogen, alkyl, alkenyl, alkynyl CN, NO¿2?, NR?4R5, (CH¿2)n cycloalkyl, (CH2)n aryl, or (CH2)n heteroaryl; R2 may further be halo; n is an integer of from 0 to 5; and R?4 and R5¿ when taken together with the nitrogen to which they are 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 R3¿ are not both selected from hydrogen and C¿1-?C6 alkyl.