3-(2,3-Dihydro-benzofuran-5-yl)-2-pyridin-2-yl-1,2,3,4-tetrahydro-pyrrolo[3,4-b]quinolin-9-one

• 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: 3-(2,3-Dihydro-benzofuran-5-yl)-2-pyridin-2-yl-1,2,3,4-tetrahydro-pyrrolo[3,4-b]quinolin-9-one
• 英文别名: 3-(2,3-dihydro-1-benzofuran-5-yl)-2-pyridin-2-yl-3,4-dihydro-1H-pyrrolo[3,4-b]quinolin-9-one
• 化学式: C₂₄H₁₉N₃O₂
• 分子量: 381.434
• InChiKey: NPQHDOLBQQVPMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-(R)-3-(2,3-dihydrobenzofuran-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one hydrogen chloride 、 2-碘吡啶 在 Pd2dba3 sodium t-butanolate 作用下， 以 1,4-二氧六环 为溶剂， 以5%的产率得到3-(2,3-Dihydro-benzofuran-5-yl)-2-pyridin-2-yl-1,2,3,4-tetrahydro-pyrrolo[3,4-b]quinolin-9-one
  参考文献：
  名称：

  Substituted pyrrolopyridinone derivatives useful as phosphodiesterase inhibitors

  摘要：

  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。

  公开号：

  US20020010183A1

文献信息

• Efficient and stereoselective process for large scale synthesis of (3R)-3-(2,3-dihydrobenzofuran-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one derivatives
  申请人：Li Xun

  公开号：US20070015798A1

  公开（公告）日：2007-01-18

  This invention relates to an efficient process for large scale stereoselective production of (3R)-3-(2,3-dihydrobenzofuran-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-ones and key intermediates used for the preparation of benzofuranyl pyrroloquinolones as potent and selective PDE5 inhibitors for the treatment of erectile dysfunction, as well as pharmaceutical compositions and methods of treatment utilizing these compounds.

  本发明涉及一种有效的大规模立体选择性生产(3R)-3-(2,3-二氢苯并呋喃-5-基)-1,2,3,4-四氢吡咯并[3,4-b]喹啉-9-酮及其在制备苯并呋喃基吡咯喹啉类PDE5抑制剂用作治疗勃起功能障碍的关键中间体方面的应用，以及利用这些化合物的制药组合物和治疗方法。
• Polymeric micromulsions
  申请人：Arien Maria Eduarda Albertina

  公开号：US20060034797A1

  公开（公告）日：2006-02-16

  The invention provides novel self-emulsifying diblock copolymers and novel self-emulsifying compositions comprising an active ingredient and a diblock copolymer characterized in that the diblock copolymer is liquid at a temperature below 50° C. and the composition is non-aqueous and liquid at a temperature below 50° C.

  本发明提供了新型自乳化二嵌段共聚物和由活性成分和二嵌段共聚物组成的新型自乳化组合物，其特征在于二嵌段共聚物在温度低于50℃时为液态，组合物在温度低于50℃时为非水性液态。
• Pyrroloquinolone PDE5 Inhibitors with Improved Pharmaceutical Profiles for Clinical Studies on Erectile Dysfunction
  作者：Weiqin Jiang、Jihua Guan、Mark J. Macielag、Suying Zhang、Yuhong Qiu、Patricia Kraft、Sheela Bhattacharjee、T. Matthew John、Donna Haynes-Johnson、Scott Lundeen、Zhihua Sui

  DOI：10.1021/jm0401098

  日期：2005.3.1

  We previously reported a series of potent and selective pyrimidinyl pyrroloquinolone PDE5 inhibitors such as 2a for potential use in male erectile dysfunction (MED) (Sui, Z.; Guan, J.; Macielag, M. J.; Jiang, W.; Zhang, S.; Qiu, Y.; Kraft, P., Bhattacharjee, S.; John, T. M.; Craig, E.; Haynes-Johnson, D.; Clancy, J. J. Med. Chem. 2002, 45, 4094-4096). Unfortunately, the low aqueous solubility and poor oral bioavailability rendered them undesirable development candidates. To address this issue, we designed a series of analogues using two approaches: increasing the overall basicity and reducing molecular weight of the lead. Through earlier SAR studies, we discovered that the PDE5 potency of the pyrroloquinolones is insensitive to substitution on the pyrrole nitrogen. Basic functional groups such as pyridines and benzimidazoles were appended via the aromatic ring connected to the pyrrole nitrogen. Several truncated analogues were also designed and synthesized to improve oral absorption. These modifications allowed us to identify analogues with good oral bioavailability in rats, dogs, and monkeys while the high potency against PDE5 and desirable selectivity versus other PDE isozymes were maintained. Compounds R-11e and R-111 were selected as development candidates for MED and other indications.
• 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
• POLYMERIC MICROEMULSIONS
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1504047A1

  公开（公告）日：2005-02-09