1-Butyl-9-[1-(4,6-dimethyl-pyrimidine-5-carbonyl)-4-methyl-piperidin-4-yl]-3-(4-fluoro-benzyl)-3,9-diaza-spiro[5.5]undecan-2-one | 1118605-43-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-Butyl-9-[1-(4,6-dimethyl-pyrimidine-5-carbonyl)-4-methyl-piperidin-4-yl]-3-(4-fluoro-benzyl)-3,9-diaza-spiro[5.5]undecan-2-one
• 英文别名: 1-Butyl-9-(1-(4,6-dimethylpyrimidine-5-carbonyl)-4-methylpiperidin-4-yl)-3-(4-fluorobenzyl)-3,9-diazaspiro[5.5]undecan-2-one；5-butyl-9-[1-(4,6-dimethylpyrimidine-5-carbonyl)-4-methylpiperidin-4-yl]-3-[(4-fluorophenyl)methyl]-3,9-diazaspiro[5.5]undecan-4-one
• CAS: 1118605-43-8
• 化学式: C₃₃H₄₆FN₅O₂
• 分子量: 563.759
• InChiKey: FUVFXKANLIQTMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  41
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  69.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  、 4,6-二甲基嘧啶-5-甲酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 1-Butyl-9-[1-(4,6-dimethyl-pyrimidine-5-carbonyl)-4-methyl-piperidin-4-yl]-3-(4-fluoro-benzyl)-3,9-diaza-spiro[5.5]undecan-2-one
  参考文献：
  名称：

  Discovery of a potent, selective and orally bioavailable 3,9-diazaspiro[5.5]undeca-2-one CCR5 antagonist

  摘要：

  Replacement of the cyclic carbamate in our previously disclosed 1-oxa-3,9-diazaspiro[5.5]undecan-2-one template led to the discovery of two novel series of 3,9-diazaspiro[5.5]undecane and undeca-2-one CCR5 antagonists. The synthesis, SAR, and antiviral activities of these two series are described. One compound (32) was found to have attractive combination of antiviral potency, selectivity, and pharmacokinetic profile. The asymmetric synthesis of 32 was also accomplished and both enantiomers were equally potent. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.115

文献信息

• Heterocyclic antiviral compounds
  申请人：Gabriel Stephen Deems

  公开号：US20090093501A1

  公开（公告）日：2009-04-09

  This invention relates to piperidine derivatives of formula I wherein R 1 , R 2 , R 3 , R 4 and Y are as defined herein useful in the treatment of a variety of disorders, including those in which the modulation of CCR5 receptors is implicated. Disorders that may be treated or prevented by the present derivatives include HIV and genetically related retroviral infections (and the resulting acquired immune deficiency syndrome, AIDS), rheumatoid arthritis, solid organ transplant reject (graft vs. host disease), asthma and COPR.

  该发明涉及式I的哌啶衍生物，其中R1、R2、R3、R4和Y如本文所定义，用于治疗多种疾病，包括那些涉及CCR5受体调节的疾病。通过目前的衍生物可治疗或预防的疾病包括HIV和遗传相关的逆转录病毒感染（及由此导致的获得性免疫缺陷综合征，艾滋病），类风湿性关节炎，固体器官移植排斥（移植物抗宿主病），哮喘和慢性阻塞性肺疾病。
• [EN] HETEROCYCLIC ANTIVIRAL COMPOUNDS<br/>[FR] COMPOSÉS ANTIVIRAUX HÉTÉROCYCLIQUES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2009037168A1

  公开（公告）日：2009-03-26

  This invention relates to piperidine derivatives of formula (I) wherein R1, R2, R3, R4 and Y are as defined herein useful in the treatment of a variety of disorders, including those in which the modulation of CCR5 receptors is implicated. Disorders that may be treated or prevented by the present derivatives include HIV and genetically related retroviral infections (and the resulting acquired immune deficiency syndrome, AIDS), rheumatoid arthritis, solid organ transplant reject (graft vs. host disease), asthma and COPR.
• Discovery of a potent, selective and orally bioavailable 3,9-diazaspiro[5.5]undeca-2-one CCR5 antagonist
  作者：Hanbiao Yang、Xiao-Fa Lin、Fernando Padilla、Stephen D. Gabriel、Gabrielle Heilek、Changhua Ji、Surya Sankuratri、André deRosier、Pamela Berry、David M. Rotstein

  DOI：10.1016/j.bmcl.2008.10.115

  日期：2009.1

  Replacement of the cyclic carbamate in our previously disclosed 1-oxa-3,9-diazaspiro[5.5]undecan-2-one template led to the discovery of two novel series of 3,9-diazaspiro[5.5]undecane and undeca-2-one CCR5 antagonists. The synthesis, SAR, and antiviral activities of these two series are described. One compound (32) was found to have attractive combination of antiviral potency, selectivity, and pharmacokinetic profile. The asymmetric synthesis of 32 was also accomplished and both enantiomers were equally potent. (C) 2008 Elsevier Ltd. All rights reserved.