1,2,3,4-Tetrahydro-2-[(4-pyridinyl)methyloxycarbonyl]-3-(3,4-methylenedioxyphenyl)-9H-pyrrolo-[3,4-b]quinolin-9-one | 663904-46-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1,2,3,4-Tetrahydro-2-[(4-pyridinyl)methyloxycarbonyl]-3-(3,4-methylenedioxyphenyl)-9H-pyrrolo-[3,4-b]quinolin-9-one
• 英文别名: 3-Benzo[1,3]dioxol-5-yl-9-oxo-1,3,4,9-tetrahydro-pyrrolo[3,4-b]quinoline-2-carboxylic acid pyridin-4-ylmethyl ester；pyridin-4-ylmethyl 3-(1,3-benzodioxol-5-yl)-9-oxo-3,4-dihydro-1H-pyrrolo[3,4-b]quinoline-2-carboxylate
• CAS: 663904-46-9
• 化学式: C₂₅H₁₉N₃O₅
• 分子量: 441.443
• InChiKey: LIXPPXSXJKCWIR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  90
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  硫酸二甲酯 、 1,2,3,4-Tetrahydro-2-[(4-pyridinyl)methyloxycarbonyl]-3-(3,4-methylenedioxyphenyl)-9H-pyrrolo-[3,4-b]quinolin-9-one 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以15%的产率得到3-Benzo[1,3]dioxol-5-yl-4-methyl-9-oxo-1,3,4,9-tetrahydro-pyrrolo[3,4-b]quinoline-2-carboxylic acid pyridin-4-ylmethyl ester
  参考文献：
  名称：

  Structure−Activity Relationships of N-Acyl Pyrroloquinolone PDE-5 Inhibitors

  摘要：

  The discovery of the potent and selective PDE-5 inhibitory activity of a pyrroloquinolone scaffold prompted us to explore the SAR of its acyl derivatives. During the course of these studies, three structural series were found with K-i values for PDE-5 in the subnanomolar range. Systematic modification of one of these leads produced a compound with excellent selectivity for PDE-5 over other phosphodiesterases and oral bioavailability of 15% in male rats. This compound also displayed in vivo efficacy in an anesthetized canine model of erection when dosed intravenously.

  DOI：

  10.1021/jm020521s
• 作为产物：
  描述：

  1-(3,4-methylenedioxyphenyl)-2,3,4,9-tetrahydro-1H-β-carboline 在 palladium on activated charcoal 盐酸 、 potassium tert-butylate 、 氢气 、 氧气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、310.26 kPa 条件下， 反应 9.0h， 生成 1,2,3,4-Tetrahydro-2-[(4-pyridinyl)methyloxycarbonyl]-3-(3,4-methylenedioxyphenyl)-9H-pyrrolo-[3,4-b]quinolin-9-one
  参考文献：
  名称：

  Structure−Activity Relationships of N-Acyl Pyrroloquinolone PDE-5 Inhibitors

  摘要：

  The discovery of the potent and selective PDE-5 inhibitory activity of a pyrroloquinolone scaffold prompted us to explore the SAR of its acyl derivatives. During the course of these studies, three structural series were found with K-i values for PDE-5 in the subnanomolar range. Systematic modification of one of these leads produced a compound with excellent selectivity for PDE-5 over other phosphodiesterases and oral bioavailability of 15% in male rats. This compound also displayed in vivo efficacy in an anesthetized canine model of erection when dosed intravenously.

  DOI：

  10.1021/jm020521s

文献信息

• Substituted pyrrolopyridinone derivatives useful as phosphodiesterase inhibitors
  申请人：——

  公开号：US20020010183A1

  公开（公告）日：2002-01-24

  The invention relates to novel pyrrolopyridinone derivatives of the formula (I) or (II): 1 pharmaceutical compositions containing the compounds and their use for the treatment of sexual dysfunction.

  这项发明涉及公式(I)或(II)的新型吡咯吡啶酮衍生物： 1 含有这些化合物的药物组合物及其用于治疗性功能障碍的用途。
• Iterative and regenerative DNA sequencing method
  申请人：The University of Iowa Research Foundation

  公开号：US20020072055A1

  公开（公告）日：2002-06-13

  An iterative and regenerative method for sequencing DNA is described. This method sequences DNA in discrete intervals starting at one end of a double stranded DNA segment. This method overcomes problems inherent in other sequencing methods, including the need for gel resolution of DNA fragments and the generation of artifacts caused by single-stranded DNA secondary structures. A particular advantage of this invention is that it can create offset collections of DNA segments and sequence the segments in parallel to provide continuous sequence information over long intervals. This method is also suitable for automation and multiplex automation to sequence large sets of segments.

  本文描述了一种用于 DNA 测序的迭代和再生方法。这种方法从双链 DNA 片段的一端开始，以离散的间隔对 DNA 进行测序。这种方法克服了其他测序方法固有的问题，包括需要对 DNA 片段进行凝胶分辨，以及由单链 DNA 二级结构引起的假象。本发明的一个特别优势是，它可以创建偏移的 DNA 片段集合，并对这些片段进行平行测序，从而在较长的时间间隔内提供连续的序列信息。这种方法也适用于自动化和多重自动化，对大量片段进行测序。
• Inhibitors of phosphodiesterases in infertility
  申请人：——

  公开号：US20040259792A1

  公开（公告）日：2004-12-23

  The present invention is directed to methods of increasing oocyte production in a mammal. More specifically, the specification describes methods and compositions for inducing follicular maturation using a PDE inhibitor. The inhibitor may be used alone at high doses. Alternatively, the follicular maturation is achieved by combining a low dose of FSH with the PDE inhibitor treatment.

  本发明涉及提高哺乳动物卵母细胞产量的方法。更具体地说，本说明书描述了使用 PDE 抑制剂诱导卵泡成熟的方法和组合物。该抑制剂可以高剂量单独使用。或者，通过将低剂量的 FSH 与 PDE 抑制剂处理相结合来实现卵泡成熟。
• INHIBITORS OF PHOSPHODIESTERASES IN INFERTILITY
  申请人：PALMER S. STEPHEN

  公开号：US20060229288A1

  公开（公告）日：2006-10-12

  The present invention is directed to methods of increasing oocyte production in a mammal. More specifically, the specification describes methods and compositions for inducing follicular maturation using a PDE inhibitor. The inhibitor may be used alone at high doses. Alternatively, the follicular maturation is achieved by combining a low dose of FSH with the PDE inhibitor treatment.

  本发明涉及提高哺乳动物卵母细胞产量的方法。更具体地说，本说明书描述了使用 PDE 抑制剂诱导卵泡成熟的方法和组合物。该抑制剂可以高剂量单独使用。或者，通过将低剂量的 FSH 与 PDE 抑制剂处理相结合来实现卵泡成熟。
• SUBSTITUTED PYRROLOPYRIDINONE DERIVATIVES USEFUL AS PHOSPHODIESTERASE INHIBITORS
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1296981B1

  公开（公告）日：2004-10-06