4-benzyl-5-oxo-4H-imidazo[1,2-a]quinazol-7-ylcarboxylic acid | 449211-42-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-benzyl-5-oxo-4H-imidazo[1,2-a]quinazol-7-ylcarboxylic acid
• 英文别名: 4-Benzyl-5-oxoimidazo[1,2-a]quinazoline-7-carboxylic acid
• CAS: 449211-42-1
• 化学式: C₁₈H₁₃N₃O₃
• 分子量: 319.32
• InChiKey: ZXINUVZOBOAVNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  75.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  O-<[cyano(ethoxycarbonyl)methylene]amino>-1,1,3,3-tetramethyluronium tetrafluoroborate 、 3,4-亚甲二氧基苄胺 、 4-benzyl-5-oxo-4H-imidazo[1,2-a]quinazol-7-ylcarboxylic acid 在 N,N-二异丙基乙胺 作用下， 以 N-甲基乙酰胺 为溶剂， 生成 4-Benzyl-5-oxo-4,5-dihydro-imidazo[1,2-a]quinazoline-7-carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide
  参考文献：
  名称：

  Triazolo compounds as MMP inhibitors

  摘要：

  从式（I）中选择的化合物：其中：W代表N或C—R1；其中R1如说明中所定义，X代表N或C—R2，其中R2如说明中所定义，Y代表从氧、硫、—NH和—N烷基中选择的基团，Z代表从氧、硫、—NR8中选择的基团，其中R8如说明中所定义，并根据Y的定义可选碳，n为0至8的整数（含0和8），Z1代表一个基团—CR9R10，其中R9和R10如说明中所定义，该基团可选地包含多个键或杂原子，A代表一个环状基团，m为0至7的整数（含0和7），基团R4如说明中所定义，R3代表从氢、烷基、烯基、炔基和式（2）所示的基团中选择的基团，其中p、Z2、B、q和R13如说明中所定义，可选地包括其外消旋体、同分异构体、N-氧化物及其药学上可接受的盐，以及含有其的药物制剂，作为第13型基质金属蛋白酶的特异性抑制剂是有用的。

  公开号：

  US20020151558A1

文献信息

• Combination of an allosteric inhibitor of matrix metalloproteinase-13 with a selective inhibitor of cyclooxygenase-2 that is not celecoxib or valdecoxib
  申请人：——

  公开号：US20040034085A1

  公开（公告）日：2004-02-19

  This invention provides a combination, comprising an allosteric inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, and 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 inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, and 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 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. The invention further provides a combination, comprising an allosteric inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with an NSAID, 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 inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with an NSAID, or a pharmaceutically acceptable salt thereof. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric 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. The invention combinations may also be further combined with other pharmaceutical agents depending on the disease being treated.

  本发明提供了一种组合物，包括MMP-13的变构抑制剂或其药学上可接受的盐，以及选择性COX-2抑制剂或其药学上可接受的盐，但不包括Celecoxib或Valdecoxib。本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，包括向患有此类疾病的患者投与包含MMP-13的变构抑制剂或其药学上可接受的盐和选择性COX-2抑制剂或其药学上可接受的盐的发明组合物。本发明还提供了一种制药组合物，包括MMP-13的变构抑制剂或其药学上可接受的盐，选择性COX-2抑制剂或其药学上可接受的盐，但不包括Celecoxib或Valdecoxib，以及药学上可接受的载体、稀释剂或赋形剂。本发明还提供了一种组合物，包括MMP-13的变构抑制剂或其药学上可接受的盐，以及NSAID或其药学上可接受的盐。本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，包括向患有此类疾病的患者投与包含MMP-13的变构抑制剂或其药学上可接受的盐和NSAID或其药学上可接受的盐的发明组合物。本发明的组合物也可以根据所治疾病进一步与其他药物组合使用。
• Method of determining potential allosterically-binding matrix metalloproteinase inhibitors
  申请人：Andrianjara Charles

  公开号：US20050004126A1

  公开（公告）日：2005-01-06

  Compounds are provided that bind allosterically to the catalytic domain of MMP-13 and comprise a hydrophobic group, first and second hydrogen bond acceptors and at least one, and preferably both, of a third hydrogen bond acceptor and a second hydrophobic group. Cartesian coordinates for centroids of the above features are defined in the specification. When the ligand binds to MMP-13, the first, second and third (when present) hydrogen bond acceptors bond respectively with Thr245, Thr 247 and Met 253, the first hydrophobic group locates within the S1′ channel of MMP-13 and the second hydrophobic group (when present) is relatively open to solvent. The compounds specifically inhibit the matrix metalloproteinase-13 enzyme and thus are useful for treating diseases resulting from tissue breakdown, such as heart disease, multiple sclerosis, arthritis, atherosclerosis, and osteoporosis.

  提供了一种与MMP-13催化域发生变构作用的化合物，其中包括一个疏水基团、第一和第二氢键受体以及至少一个第三氢键受体和第二个疏水基团，最好是两者都有。上述特征的笛卡尔坐标在说明书中有定义。当配体与MMP-13结合时，第一、第二和第三（存在时）氢键受体分别与Thr245、Thr 247和Met 253结合，第一疏水基团位于MMP-13的S1'通道内，第二疏水基团（存在时）相对于溶剂较为开放。这些化合物特异性地抑制了基质金属蛋白酶-13酶，因此可用于治疗由组织分解引起的疾病，如心脏病、多发性硬化症、关节炎、动脉粥样硬化和骨质疏松症。
• Combination of an allosteric inhibitor of matrix metalloproteinase-13 with celecoxib or valdecoxib
  申请人：——

  公开号：US20040034086A1

  公开（公告）日：2004-02-19

  This invention provides a combination, comprising an allosteric 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. This invention also provides a pharmaceutical composition, comprising the invention combination 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.

  本发明提供了一种组合物，包括MMP-13的异位抑制剂或其药学上可接受的盐与塞来昔布或其药学上可接受的盐或缬癸昔布或其药学上可接受的盐。本发明还提供了一种治疗对抑制 MMP-13 和环氧合酶-2 有反应的疾病的方法，包括向患有此类疾病的患者施用本发明的组合物。本发明还提供了一种药物组合物，包括本发明组合物和药学上可接受的载体、稀释剂或赋形剂。本发明组合物还可根据治疗的疾病进一步与其他药剂组合。
• TRIAZOLO COMPOUNDS AS MMP INHIBITORS
  申请人：Warner-Lambert Company LLC

  公开号：EP1362048B1

  公开（公告）日：2005-05-04
• COMBINATION OF AN ALLOSTERIC INHIBITOR OF MATRIX METALLOPROTEINASE-13 WITH A SELECTIVE INHIBITOR OF CYCLOOXYGENASE-2 THAT IS NOT CELECOXIB OR VALDECOXIB
  申请人：Warner-Lambert Company LLC

  公开号：EP1531904A1

  公开（公告）日：2005-05-25