1-[4-bromo-2-((3R,5S)-3,5-dimethyl-piperidine-1-carbonyl)-phenyl]-3-(1,5-dimethyl-1H-pyrazol-3-ylmethyl)-urea | 1034257-58-3

• 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: 1-[4-bromo-2-((3R,5S)-3,5-dimethyl-piperidine-1-carbonyl)-phenyl]-3-(1,5-dimethyl-1H-pyrazol-3-ylmethyl)-urea
• 英文别名: 1-[4-bromo-2-[(3R,5S)-3,5-dimethylpiperidine-1-carbonyl]phenyl]-3-[(1,5-dimethylpyrazol-3-yl)methyl]urea
• CAS: 1034257-58-3
• 化学式: C₂₁H₂₈BrN₅O₂
• 分子量: 462.39
• InChiKey: OQEKYELXYCFLIO-OKILXGFUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  79.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (1,5-二甲基-1H-吡咯-3-基)甲胺 、 光气 、 (2-氨基-5-溴苯基)((3R,5S)-3,5-二甲基哌啶-1-基)甲酮 在 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 生成 1-[4-bromo-2-((3R,5S)-3,5-dimethyl-piperidine-1-carbonyl)-phenyl]-3-(1,5-dimethyl-1H-pyrazol-3-ylmethyl)-urea
  参考文献：
  名称：

  Fragment-based discovery of hepatitis C virus NS5b RNA polymerase inhibitors

  摘要：

  Non-nucleoside inhibitors of HCV NS5b RNA polymerase were discovered by a fragment-based lead discovery approach, beginning with crystallographic fragment screening. The NS5b binding affinity and biochemical activity of fragment hits and inhibitors was determined by surface plasmon resonance (Biacore) and an enzyme inhibition assay, respectively. Crystallographic fragment screening hits with approximately 1-10mM binding affinity (K(D)) were iteratively optimized to give leads with approximately 200nM biochemical activity and low microM cellular activity in a Replicon assay.

  DOI：

  10.1016/j.bmcl.2008.03.056

文献信息

• Hepatitis C virus polymerase inhibitors
  申请人：Blaney Jeffrey Mark

  公开号：US20080200512A1

  公开（公告）日：2008-08-21

  The invention provides a compound of formula: and methods for making and using the same, where R 1 and R 2 are independently hydrogen, C 1-6 alkyl or C 1-6 haloalkyl; R 3 is hydrogen, halogen, C 1-6 alkyl or C 1-6 alkoxy; R 4 is hydrogen or halogen; and R 5 is a mono- or di-amino acid moiety, a succinic acid moiety, a urea moiety, or a derivative thereof. The invention also provides pharmaceutical compositions comprising a compound of formula I, and methods for making and using the same.

  这项发明提供了一个化合物的公式：以及制备和使用该化合物的方法，其中R1和R2分别是氢、C1-6烷基或C1-6卤代烷基；R3是氢、卤素、C1-6烷基或C1-6烷氧基；R4是氢或卤素；R5是单氨基酸或双氨基酸基团、琥珀酸基团、尿素基团或其衍生物。该发明还提供了包含化合物I的药物组合物，以及制备和使用该药物组合物的方法。
• Fragment-based discovery of hepatitis C virus NS5b RNA polymerase inhibitors
  作者：Stephen S. Antonysamy、Brandon Aubol、Jeff Blaney、Michelle F. Browner、Anthony M. Giannetti、Seth F. Harris、Normand Hébert、Jörg Hendle、Stephanie Hopkins、Elizabeth Jefferson、Charles Kissinger、Vincent Leveque、David Marciano、Ethel McGee、Isabel Nájera、Brian Nolan、Masaki Tomimoto、Eduardo Torres、Tobi Wright

  DOI：10.1016/j.bmcl.2008.03.056

  日期：2008.5

  Non-nucleoside inhibitors of HCV NS5b RNA polymerase were discovered by a fragment-based lead discovery approach, beginning with crystallographic fragment screening. The NS5b binding affinity and biochemical activity of fragment hits and inhibitors was determined by surface plasmon resonance (Biacore) and an enzyme inhibition assay, respectively. Crystallographic fragment screening hits with approximately 1-10mM binding affinity (K(D)) were iteratively optimized to give leads with approximately 200nM biochemical activity and low microM cellular activity in a Replicon assay.