2-(dimethylamino)ethyl 4-fluoro-6-((7-fluoro-4-oxo-3,4-dihydroquinazolin-6-yl)methyl)-8-(2-oxo-1,2-dihydropyridin-3-yl)-6H-furo[2,3-e]indole-7-carboxylate hydrochloride | 1199813-69-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-(dimethylamino)ethyl 4-fluoro-6-((7-fluoro-4-oxo-3,4-dihydroquinazolin-6-yl)methyl)-8-(2-oxo-1,2-dihydropyridin-3-yl)-6H-furo[2,3-e]indole-7-carboxylate hydrochloride
• 英文别名: SCH 900782；2-(dimethylamino)ethyl 4-fluoro-6-[(7-fluoro-4-oxo-3H-quinazolin-6-yl)methyl]-8-(2-oxo-1H-pyridin-3-yl)furo[2,3-e]indole-7-carboxylate;hydrochloride
• CAS: 1199813-69-8
• 化学式: C₂₉H₂₃F₂N₅O₅*ClH
• 分子量: 595.99
• InChiKey: SBPZEKXNTHXZDK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.45
• 重原子数：
  42
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  [7-fluoro-6-[(4-fluoro-7-oxofuro[2,3-e]pyrido[3',2':5,6]pyrano[3,4-b]indol-6(7H)-yl)methyl]-4-oxo-3(4H)-quinazolinyl]methyl 2,2-dimethylpropanoate 在 盐酸 、 正丁基锂 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 4.5h， 生成 2-(dimethylamino)ethyl 4-fluoro-6-((7-fluoro-4-oxo-3,4-dihydroquinazolin-6-yl)methyl)-8-(2-oxo-1,2-dihydropyridin-3-yl)-6H-furo[2,3-e]indole-7-carboxylate hydrochloride
  参考文献：
  名称：

  Discovery of SCH 900188: A Potent Hepatitis C Virus NS5B Polymerase Inhibitor Prodrug As a Development Candidate

  摘要：

  Starting from indole-based hepatitis C virus (HCV) NS5B polymerase inhibitor lead compound 1, structure modifications were performed at multiple indole substituents to improve potency and pharmacokinetic (PK) properties. Bicyclic quinazolinone was found to be the best substituent at indole nitrogen, while 4,5-furanylindole was identified as the best core. Compound 11 demonstrated excellent potency. Its C2 N,N-dimethylaminoethyl ester prodrug 12 (SCH 900188) demonstrated significant improvement in PK and was selected as the development candidate.

  DOI：

  10.1021/ml400192w

文献信息

• [EN] TRICYCLIC INDOLE DERIVATIVES AND METHODS OF USE THEREOF<br/>[FR] DÉRIVÉS D'INDOLE TRICYCLIQUES ET PROCÉDÉS D'UTILISATION DE CEUX-CI
  申请人：SCHERING CORP

  公开号：WO2009152200A1

  公开（公告）日：2009-12-17

  The present invention relates to Tricyclic Indole Derivatives, compositions comprising at least one Tricyclic Indole Derivatives, and methods of using the Tricyclic Indole Derivatives for treating or preventing a viral infection or a virus-related disorder in a patient

  本发明涉及三环吲哚衍生物，包括至少一种三环吲哚衍生物的组合物，以及利用该三环吲哚衍生物治疗或预防患者病毒感染或与病毒相关的疾病的方法。
• Discovery of SCH 900188: A Potent Hepatitis C Virus NS5B Polymerase Inhibitor Prodrug As a Development Candidate
  作者：Kevin X. Chen、Srikanth Venkatraman、Gopinadhan N. Anilkumar、Qingbei Zeng、Charles A. Lesburg、Bancha Vibulbhan、Francisco Velazquez、Tin-Yau Chan、Frank Bennet、Yueheng Jiang、Patrick Pinto、Yuhua Huang、Oleg Selyutin、Sony Agrawal、Hsueh-Cheng Huang、Cheng Li、Kuo-Chi Cheng、Neng-Yang Shih、Joseph A. Kozlowski、Stuart B. Rosenblum、F. George Njoroge

  DOI：10.1021/ml400192w

  日期：2014.3.13

  Starting from indole-based hepatitis C virus (HCV) NS5B polymerase inhibitor lead compound 1, structure modifications were performed at multiple indole substituents to improve potency and pharmacokinetic (PK) properties. Bicyclic quinazolinone was found to be the best substituent at indole nitrogen, while 4,5-furanylindole was identified as the best core. Compound 11 demonstrated excellent potency. Its C2 N,N-dimethylaminoethyl ester prodrug 12 (SCH 900188) demonstrated significant improvement in PK and was selected as the development candidate.