JNJ-10280205 | 374927-06-7

• 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: JNJ-10280205
• 英文别名: 3-(2,3-dihydro-5-benzofuranyl)-1,2,3,4-tetrahydro-2-[5-(2-pyridinyl)-2-pyrimidinyl]-(3R)-9H-pyrrolo[3,4-b]quinolin-9-one；(3R)-3-(2,3-dihydro-1-benzofuran-5-yl)-2-(5-pyridin-2-ylpyrimidin-2-yl)-3,4-dihydro-1H-pyrrolo[3,4-b]quinolin-9-one
• CAS: 374927-06-7
• 化学式: C₂₈H₂₁N₅O₂
• 分子量: 459.507
• InChiKey: WQUZPRFCWILZJO-AREMUKBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  35
• 可旋转键数：
  3
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  80.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  JNJ-10280205 在 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 以10%的产率得到3-(2,3-Dihydro-benzofuran-5-yl)-2-[5-(1-oxy-pyridin-2-yl)-pyrimidin-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
• 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-氯-5-吡啶-2-基嘧啶 在 potassium fluoride 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 以85%的产率得到JNJ-10280205
  参考文献：
  名称：

  Pyrroloquinolone PDE5 Inhibitors with Improved Pharmaceutical Profiles for Clinical Studies on Erectile Dysfunction

  摘要：

  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.

  DOI：

  10.1021/jm0401098

文献信息

• Cyclic protein tyrosine kinase inhibitors
  申请人：Barrish C. Joel

  公开号：US20050288303A1

  公开（公告）日：2005-12-29

  Novel cyclic compounds and salts thereof, pharmaceutical compositions containing such compounds, and methods of using such compounds in the treatment of protein tyrosine kinase-associated disorders such as immunologic and oncologic disorders.

  小说环状化合物及其盐，含有这些化合物的制药组合物，以及使用这些化合物治疗蛋白酪氨酸激酶相关疾病（如免疫和肿瘤性疾病）的方法。
• COMPOUNDS FOR THE TREATMENT OF COVID-19
  申请人：Dompe' Farmaceutici S.P.A.

  公开号：EP3875078A1

  公开（公告）日：2021-09-08

  The present invention relates to compounds that are able to inhibt 3CL protease of COVID-19 virus, SARS-Cov-2

  本发明涉及能够抑制 COVID-19 病毒、SARS-Cov-2 病毒的 3CL 蛋白酶的化合物。
• SUBSTITUTED PYRROLOPYRIDINONE DERIVATIVES USEFUL AS PHOSPHODIESTERASE INHIBITORS
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1296981A2

  公开（公告）日：2003-04-02
• US6635638B2
  申请人：——

  公开号：US6635638B2

  公开（公告）日：2003-10-21
• US6818646B2
  申请人：——

  公开号：US6818646B2

  公开（公告）日：2004-11-16