methyl 2-[4-({[2-[2-(2,4-difluorophenyl)ethyl]-4-oxo-1(4H)-quinazolinyl]acetyl}{[4'-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]-2-methylpropanoate | 1019658-03-7

• 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: methyl 2-[4-({[2-[2-(2,4-difluorophenyl)ethyl]-4-oxo-1(4H)-quinazolinyl]acetyl}{[4'-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]-2-methylpropanoate
• 英文别名: methyl 2-[4-({[2-[2-(2,4-difluorophenyl)ethyl]-4-oxo-1(4H)-quinazolinyl]acetyl}-{[4'-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]-2-methylpropanoate；methyl 2-[4-({[2-[2-(2,4-difluorophenyl)ethyl]-4-oxo-1(4H)-quinazolinyl]acetyl} {[4'-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]-2-methylpropanoate；methyl 2-[4-[[2-[2-[2-(2,4-difluorophenyl)ethyl]-4-oxoquinazolin-1-yl]acetyl]-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]amino]piperidin-1-yl]-2-methylpropanoate
• CAS: 1019658-03-7
• 化学式: C₄₂H₄₁F₅N₄O₄
• 分子量: 760.804
• InChiKey: DDXZVKBGKWYFGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  55
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  82.5
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-溴代异丁酸甲酯 在 三乙酰氧基硼氢化钠 、 potassium carbonate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 18.5h， 生成 methyl 2-[4-({[2-[2-(2,4-difluorophenyl)ethyl]-4-oxo-1(4H)-quinazolinyl]acetyl}{[4'-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]-2-methylpropanoate
  参考文献：
  名称：

  METHODS OF TREATMENT AND PREVENTION OF NEURODEGENERATIVE DISEASES AND DISORDERS

  摘要：

  本发明提供了一种用于治疗和预防神经退行性疾病和神经相关疾病的组合物和方法，通过抑制Lp-PLA2。这些组合物和方法可用于治疗和预防具有异常血脑屏障（BBB）功能的疾病和疾病，例如具有可渗透BBB的神经退行性疾病，如但不限于阿尔茨海默病、亨廷顿病、帕金森病和血管性痴呆症。

  公开号：

  EP2977452A3

文献信息

• METHODS OF TREATMENT AND PREVENTION OF METABOLIC BONE DISEASES AND DISORDERS
  申请人：SHI Yi

  公开号：US20080280829A1

  公开（公告）日：2008-11-13

  The present invention provides compostions and methods useful for treating and preventing metabolic bone diseases and disorders by inhibition of Lp-PLA 2 . The compositions and methods are useful for treating and preventing metabolic bone diseases and disorders such as, for example osteoporosis, osteopenia and osteopenia related diseases and abnormal bone marrow.

  本发明提供了用于治疗和预防代谢性骨疾病和紊乱的组合物和方法，通过抑制Lp-PLA2。这些组合物和方法可用于治疗和预防代谢性骨疾病和紊乱，例如骨质疏松症、骨质疏松症和相关疾病以及异常骨髓。
• Bicyclic Heteroaromatic Compounds
  申请人：LEACH Colin Andrew

  公开号：US20080090853A1

  公开（公告）日：2008-04-17

  A compound of formula (I) wherein: R 1 is an aryl group, unsubstituted or substituted by 1, 2, 3 or 4 substituents which may be the same or different selected from the group consisting of C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, aryl C 1 -C 6 alkoxy, hydroxy, halo, CN, COR 6 , COOR 6 , NR 6 COR 7 , CONR 8 R 9 , SO 2 NR 8 R 9 , NR 6 SO 2 R 7 , NR 8 R 9 , halo C 1 -C 4 alkyl, and halo C 1 -C 4 alkoxy; W is CH and X is N, or W is N and X is CH, or W and X are CH; Y is C 2 -C 4 alkyl, R 2 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, aryl C 1 -C 6 alkoxy, hydroxy, halo, CN, COR 6 , carboxy, COOR 6 , NR 6 COR 7 , CONR 8 R 9 , SO 2 NR 8 R 9 , NR 6 SO 2 R 7 , NR 8 R 9 , mono to perfluoro-C 1 -C 6 alkyl, or mono to perfluoro-C 1 -C 6 alkoxy; n is 0-5; R 3 is C 1 -C 4 alkyl; R 4 is C 1 -C 4 alkyl; R 5 is hydrogen, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, halo C 1 -C 4 alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl C 1 -C 4 alkyl, C 5 -C 8 cycloalkenyl, C 5 -C 8 cycloalkenyl C 1 -C 4 alkyl, 3-8-membered heterocycloalkyl, 3-8-membered heterocycloalkyl C 1 -C 4 alkyl, C 6 -C 14 aryl, C 6 -C 14 aryl C 1 -C 10 alkyl, heteroaryl, or heteroaryl C 1 -C 10 alkyl; wherein each group is optionally one or more times by the same and/or a different group which is C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, aryl C 1 -C 6 alkoxy, hydroxy, halo, CN, NR 8 R 9 , or halo C 1 -C 4 alkoxy R 6 and R 7 are independently hydrogen or C 1 -C 10 alkyl; R 8 and R 9 are the same or different and are hydrogen or C 1 -C 10 alkyl, or R 9 and R 10 together with the nitrogen to which they are attached form a 5- to 7 membered ring optionally containing one or more further heteroatoms selected from oxygen, nitrogen and sulphur, and optionally substituted by one or two substituents selected from the group consisting of hydroxy, oxo, C 1 -C 4 alkyl, C 1 -C 4 alkylcarboxy, aryl, and aryl C 1 -C 4 alkyl; or a pharmaceutically acceptable salt thereof. These compounds are useful for treating atherosclerosis or other inflammatory diseases.

  式（I）的化合物中：R1是芳基，未取代或通过1、2、3或4个取代基取代，这些取代基可以是相同的或不同的，选自C1-C6烷基、C1-C6烷氧基、C1-C6烷硫基、芳基C1-C6烷氧基、羟基、卤素、CN、COR6、COOR6、NR6COR7、CONR8R9、SO2NR8R9、NR6SO2R7、NR8R9、卤代C1-C4烷基和卤代C1-C4烷氧基；W为CH，X为N，或W为N，X为CH，或W和X均为CH；Y为C2-C4烷基，R2为氢、C1-C6烷基、C1-C6烷氧基、C1-C6烷硫基、芳基C1-C6烷氧基、羟基、卤素、CN、COR6、羧基、COOR6、NR6COR7、CONR8R9、SO2NR8R9、NR6SO2R7、NR8R9、单氟至全氟C1-C6烷基或单氟至全氟C1-C6烷氧基；n为0-5；R3为C1-C4烷基；R4为C1-C4烷基；R5为氢、C1-C10烷基、C2-C10烯基、C2-C10炔基、卤代C1-C4烷基、C3-C8环烷基、C3-C8环烷基、C3-C8环烷基C1-C4烷基、C5-C8环烯基、C5-C8环烯基C1-C4烷基、3-8环杂环烷基、3-8环杂环烷基C1-C4烷基、C6-C14芳基、C6-C14芳基C1-C10烷基、杂芳基或杂芳基C1-C10烷基；其中每个基可以选择性地通过相同和/或不同的基取代一次或多次，该基为C1-C6烷氧基、C1-C6烷硫基、芳基C1-C6烷氧基、羟基、卤素、CN、NR8R9或卤代C1-C4烷氧基；R6和R7独立地是氢或C1-C10烷基；R8和R9相同或不同，是氢或C1-C10烷基，或R9和R10连同它们连接的氮原子形成一个5-至7-成员环，该环可以包含一个或多个进一步的氧、氮和硫杂原子，并且可以通过羟基、氧代、C1-C4烷基、C1-C4烷基羧基、芳基和芳基C1-C4烷基中的一个或两个取代基取代；或其药学上可接受的盐。这些化合物可用于治疗动脉粥样硬化或其他炎症性疾病。
• METHODS OF TREATMENT OF SKIN ULCERS
  申请人：Wilensky Robert

  公开号：US20100239565A1

  公开（公告）日：2010-09-23

  Methods for treating and/or preventing skin ulcers are provided featuring administration of pharmaceutical compositions comprising inhibitors of activity or expression Of Lp-PLA 2 protein to patients subject to or at risk of developing skin ulcers.

  提供了治疗和/或预防皮肤溃疡的方法，其中包括给予含有Lp-PLA2蛋白质活性或表达抑制剂的药物组合物给予患有或有发展皮肤溃疡风险的患者。
• Methods of treatment and prevention of metabolic bone diseases and disorders
  申请人：Shi Yi

  公开号：US08962633B2

  公开（公告）日：2015-02-24

  The present invention provides compostions and methods useful for treating and preventing metabolic bone diseases and disorders by inhibition of Lp-PLA2. The compositions and methods are useful for treating and preventing metabolic bone diseases and disorders such as, for example osteoporosis, osteopenia and osteopenia related diseases and abnormal bone marrow.

  本发明提供了用于治疗和预防代谢性骨疾病和疾病的组合物和方法，通过抑制Lp-PLA2。这些组合物和方法适用于治疗和预防代谢性骨疾病和疾病，例如骨质疏松症、骨质疏松和骨髓异常相关的疾病。
• Methods of treatment of skin ulcers
  申请人：Wilensky Robert

  公开号：US09029383B2

  公开（公告）日：2015-05-12

  Methods for treating and/or preventing skin ulcers are provided featuring administration of pharmaceutical compositions comprising inhibitors of activity or expression Of Lp-PLA2 protein to patients subject to or at risk of developing skin ulcers.

  提供了治疗和/或预防皮肤溃疡的方法，其中包括向患有或有发生皮肤溃疡风险的患者给予含有Lp-PLA2蛋白酶活性或表达抑制剂的药物组合物。