N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxo-2H-pyrimidin-1-yl)-cyclopentyl]-4-bromo-benzenesulfonamide | 1034172-22-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxo-2H-pyrimidin-1-yl)-cyclopentyl]-4-bromo-benzenesulfonamide
• 英文别名: N-((1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl)-3-bromobenzenesulfonamide；N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1-yl)cyclopentyl]-3-bromobenzenesulfonamide
• CAS: 1034172-22-9
• 化学式: C₁₅H₁₆BrFN₄O₃S
• 分子量: 431.285
• InChiKey: ATZVSSYRFNGGBF-QWRGUYRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxo-2H-pyrimidin-1-yl)-cyclopentyl]-4-bromo-benzenesulfonamide 、 4-氯-2-甲基苯硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 作用下， 以 水 、 乙腈 为溶剂， 生成 N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1-yl)cyclopentyl]-3-(4-chloro-2-methylphenyl)benzenesulfonamide
  参考文献：
  名称：

  Lead optimization and structure-based design of potent and bioavailable deoxycytidine kinase inhibitors

  摘要：

  A series of deoxycytidine kinase inhibitors was simultaneously optimized for potency and PK properties. A co-crystal structure then allowed merging this series with a high throughput screening hit to afford a highly potent, selective and orally bioavailable inhibitor, compound 10. This compound showed dose dependent inhibition of deoxycytidine kinase in vivo. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.09.081
• 作为产物：
  描述：

  tert-butyl N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1-yl)cyclopentyl]-N-(3-bromophenyl)sulfonylcarbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxo-2H-pyrimidin-1-yl)-cyclopentyl]-4-bromo-benzenesulfonamide
  参考文献：
  名称：

  Lead optimization and structure-based design of potent and bioavailable deoxycytidine kinase inhibitors

  摘要：

  A series of deoxycytidine kinase inhibitors was simultaneously optimized for potency and PK properties. A co-crystal structure then allowed merging this series with a high throughput screening hit to afford a highly potent, selective and orally bioavailable inhibitor, compound 10. This compound showed dose dependent inhibition of deoxycytidine kinase in vivo. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.09.081

文献信息

• 4-AMINO-1H-PYRIMIDIN-2-ONE BASED COMPOUNDS, COMPOSITIONS COMPRISING THEM AND METHODS OF THEIR USE
  申请人：Augeri David J.

  公开号：US20080182847A1

  公开（公告）日：2008-07-31

  4-Amino-1H-pyrimidin-2-one-based compounds, compositions comprising them, and methods of their use for the treatment, prevention and management of various diseases and disorders are disclosed. Particular compounds are of formula I:

  本发明涉及基于4-氨基-1H-嘧啶-2-酮的化合物，包括这些化合物的组合物，以及它们在治疗、预防和管理各种疾病和疾病障碍方面的使用方法。具体化合物的化学式为I:
• WO2008/76778
  申请人：——

  公开号：——

  公开（公告）日：——
• US8093245B2
  申请人：——

  公开号：US8093245B2

  公开（公告）日：2012-01-10
• [EN] 4-AMINO-1H-PYRIMIDIN-2-ONE BASED COMPOUNDS, COMPOSITIONS COMPRISING THEM, AND METHODS OF THEIR USE<br/>[FR] COMPOSÉS À BASE DE 4-AMINO-1H-PYRIMIDINE-2-ONE, COMPOSITIONS LES CONTENANT ET PROCÉDÉS D'UTILISATION DE CEUX-CI
  申请人：LEXICON PHARMACEUTICALS INC

  公开号：WO2008076778A1

  公开（公告）日：2008-06-26

  [EN] 4-Amino-1H-pyrimidin-2-one-based compounds, compositions comprising them, and methods of their use for the treatment, prevention and management of various diseases and disorders are disclosed. Particular compounds are of formula (I).
  [FR] L'invention concerne des composés à base de 4-Amino-1H-pyrimidine-2-one, des compositions les contenant et des procédés d'utilisation de ceux-ci dans le traitement, la prévention et la gestion de divers troubles et maladies. Des composés particuliers sont représentés par la formule (I).
• Lead optimization and structure-based design of potent and bioavailable deoxycytidine kinase inhibitors
  作者：Theodore C. Jessop、James E. Tarver、Marianne Carlsen、Amy Xu、Jason P. Healy、Alexander Heim-Riether、Qinghong Fu、Jerry A. Taylor、David J. Augeri、Min Shen、Terry R. Stouch、Ronald V. Swanson、Leslie W. Tari、Michael Hunter、Isaac Hoffman、Philip E. Keyes、Xuan-Chuan Yu、Maricar Miranda、Qingyun Liu、Jonathan C. Swaffield、S. David Kimball、Amr Nouraldeen、Alan G.E. Wilson、Ann Marie DiGeorge Foushee、Kanchan Jhaver、Rick Finch、Steve Anderson、Tamas Oravecz、Kenneth G. Carson

  DOI：10.1016/j.bmcl.2009.09.081

  日期：2009.12

  A series of deoxycytidine kinase inhibitors was simultaneously optimized for potency and PK properties. A co-crystal structure then allowed merging this series with a high throughput screening hit to afford a highly potent, selective and orally bioavailable inhibitor, compound 10. This compound showed dose dependent inhibition of deoxycytidine kinase in vivo. (C) 2009 Elsevier Ltd. All rights reserved.