8-methyl-2-[5-[(E)-3-(4-methylpiperazin-1-yl)-3-oxoprop-1-enyl]-2-propoxyphenyl]-3H-quinazolin-4-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 8-methyl-2-[5-[(E)-3-(4-methylpiperazin-1-yl)-3-oxoprop-1-enyl]-2-propoxyphenyl]-3H-quinazolin-4-one
• 化学式: C₂₆H₃₀N₄O₃
• 分子量: 446.5
• InChiKey: JMBKUDXMIKPBIU-PKNBQFBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  4

文献信息

• Methods and compositions for nucleic acid delivery
  申请人：Johns Hopkins University

  公开号：US20020094326A1

  公开（公告）日：2002-07-18

  The present provides methods and compositions that enable effective delivery of nucleic acids to desired cells, including to a solid organ such as a mammalian heart. The methods and compositions enable effective gene transfer and subsequent expression to a majority of cells throughout a solid organ such as the heart. Methods and compositions of the invention preferably provide enhanced vascular permeability that enables increased gene transfer to targeted cells, but without significant degradation or injury to endothelial cell layers.

  本文提供了一种方法和组合物，可以有效地将核酸传递到所需的细胞，包括哺乳动物心脏等固体器官。这些方法和组合物可以实现有效的基因转移，并随后在固体器官（如心脏）的大多数细胞中表达。本发明的方法和组合物最好提供增强的血管通透性，从而使基因转移到靶向细胞的数量增加，但不会对内皮细胞层造成显著的降解或损伤。
• Methods for prevention and treatment of gastrointestinal disorders
  申请人：——

  公开号：US20020128171A1

  公开（公告）日：2002-09-12

  Disclosed are methods for preventing or treating a gastrointestinal (GI) disorder in a mammal such as a human patient. In one embodiment, the methods include administering to the mammal a therapeutically effective amount of a compound that modulates a nitric oxide (NO) signaling pathway, particularly in GI neurons. Methods of the invention are particularly useful for the treatment (including prophylactic treatment) of diabetic gastropathies and other GI disorders.

  本发明涉及一种预防或治疗哺乳动物（例如人类患者）胃肠道（GI）疾病的方法。在一种实施例中，该方法包括向哺乳动物（特别是GI神经元）中投与治疗效果的化合物，该化合物调节一氧化氮（NO）信号通路的数量。本发明的方法对于治疗（包括预防性治疗）糖尿病性胃病和其他GI疾病特别有用。
• cGMP PDE 5 Inhibitors for inhalation in the treatment of sexual dysfunction
  申请人：——

  公开号：US20010055570A1

  公开（公告）日：2001-12-27

  Treatment of sexual dysfunction by inhalation of a cGMP PDE 5 inhibitor, especially 5-[2-ethoxy-5-(4-methylpiperazinylsulfonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one, 4-phenylmethylamino-6-chloro-2-(1-imidazolyl) quinazoline, 4-phenylmethylamino-6-chloro-2-(3-pyridyl) quinazoline, 1,3-dimethyl-6-(2-propoxy-5-methanesulfonylamidophenyl)-1,5-dihydropyrazolo[3,4-d]pyrimidin-4-one or 1-cyclopentyl-3-ethyl-6-(3-ethoxy-4-pyridyl)-pyrazolo[3,4-d]pyrimidin-4-one.

  通过吸入cGMP PDE 5抑制剂治疗性功能障碍，特别是5-[2-乙氧基-5-(4-甲基哌嗪磺酰基)苯基]-1-甲基-3-正丙基-1,6-二氢-7H-吡唑并[4,3-d]嘧啶-7-酮、4-苯甲基氨基-6-氯-2-(1-咪唑基)喹唑啉、4-苯甲基氨基-6-氯-2-(3-吡啶基)喹唑啉、1,3-二甲基-6-(2-丙氧基-5-甲烷磺酰胺基苯基)-1,5-二氢-吡唑并[3,4-d]嘧啶-4-酮或1-环戊基-3-乙基-6-(3-乙氧基-4-吡啶基)-吡唑并[3,4-d]嘧啶-4-酮。
• cGMP PDE 5 inhibitors for inhalation in the treatment of sexual dysfunction
  申请人：——

  公开号：US20040214831A1

  公开（公告）日：2004-10-28

  Treatment of sexual dysfunction by inhalation of a cGMP PDE 5 inhibitor, especially 5-[2-ethoxy-5-(4-methylpiperazinylsulfonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one, 4-phenylmethylamino-6-chloro-2-(1-imidazolyl) quinazoline, 4-phenylmethylamino-6-chloro-2-(3-pyridyl) quinazoline, 1,3-dimethyl-6-(2-propoxy-5-methanesulfonylamidophenyl)-1,5-dihydropyrazolo[3,4-d]pyrimidin-4-one or 1-cyclopentyl-3-ethyl-6-(3-ethoxy-4-pyridyl)-pyrazolo[3,4-d]pyrimidin-4-one.

  通过吸入cGMP PDE 5抑制剂治疗性功能障碍，特别是5-[2-乙氧基-5-(4-甲基哌嗪磺酰基)苯基]-1-甲基-3-正丙基-1,6-二氢-7H-吡唑并[4,3-d]嘧啶-7-酮，4-苯甲氨基-6-氯-2-(1-咪唑基)喹唑啉，4-苯甲氨基-6-氯-2-(3-吡啶基)喹唑啉，1,3-二甲基-6-(2-丙氧基-5-甲磺酰胺基苯基)-1,5-二氢-吡唑并[3,4-d]嘧啶-4-酮或1-环戊基-3-乙基-6-(3-乙氧基-4-吡啶基)-吡唑并[3,4-d]嘧啶-4-酮。
• Pharmaceutical compositions for treating nitrate-induced tolerance
  申请人：Pfizer Limited

  公开号：EP1022026A2

  公开（公告）日：2000-07-26

  The present invention relates to methods for treating nitrate-induced tolerance in a mammal by administering a nitrate-induced tolerance treating amount of a compound of formulae (I), (II), (III) (IV), (V), (VI), (VII), (VIII), (IX), (XA) or (XB) as defined herein, or the pharmaceutically acceptable salts, prodrugs, polymorphs, hydrates, solvates, active metabolites or stereoisomers thereof. The invention also relates to pharmaceutical compositions for the treatment of nitrate-induced tolerance in a mammal comprising a nitrate-induced tolerance treating amount of a compound of formulae (I), (II), (III) (lV), (V), (VI), (VII), (VIII), (IX), (XA) or (XB) as defined herein, or the pharmaceutically acceptable salts, prodrugs, polymorphs, hydrates, solvates, active metabolites or stereoisomers thereof, and a pharmaceutically acceptable vehicle, diluent or carrier. The invention further relates to methods of preventing nitrate-induced tolerance in a mammal comprising administering a nitrate-induced tolerance preventing amount of a cGMP PDE inhibitor.

  本发明涉及通过施用本文定义的式(I)、(II)、(III)(IV)、(V)、(VI)、(VII)、(VIII)、(IX)、(XA)或(XB)化合物或其药学上可接受的盐、原药、多晶型物、水合物、溶解物、活性代谢物或立体异构体的硝酸盐诱导的耐受性治疗量来治疗哺乳动物的硝酸盐诱导的耐受性的方法。本发明还涉及用于治疗哺乳动物硝酸盐诱导耐受性的药物组合物，其包含硝酸盐诱导耐受性治疗量的式(I)、(II)、(III)(lV)、(V)、(VI)、(VII)、(VIII)、(IX)、(XA)或(XB)，或其药学上可接受的盐、原药、多晶型物、水合物、溶解物、活性代谢物或立体异构体，以及药学上可接受的载体、稀释剂或载体。本发明还涉及防止哺乳动物产生硝酸盐耐受性的方法，包括施用一定量的 cGMP PDE 抑制剂，以防止产生硝酸盐耐受性。