tert-butyl 4-(6-chloropyrimidin-4-yl)piperidine-1-carboxylate | 954232-45-2

• 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: tert-butyl 4-(6-chloropyrimidin-4-yl)piperidine-1-carboxylate
• CAS: 954232-45-2
• 化学式: C₁₄H₂₀ClN₃O₂
• 分子量: 297.785
• InChiKey: ROQUICCMYRNFIT-UHFFFAOYSA-N

物化性质

• 沸点：
  407.5±45.0 °C(Predicted)
• 密度：
  1.204±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  55.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(6-chloropyrimidin-4-yl)piperidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 4-(6-chloropyrimidin-4-yl)piperidine hydrochloride
  参考文献：
  名称：

  [EN] INDAZOLYL-SPIRO[2.2]PENTANE-CARBONITRILE DERIVATIVES AS LRRK2 INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF
  [FR] DÉRIVÉS D'INDAZOLYL-SPIRO [2.2] PENTANE-CARBONITRILE EN TANT QU'INHIBITEURS DE LRRK2, COMPOSITIONS PHARMACEUTIQUES ET LEURS UTILISATIONS

  摘要：

  本发明涉及Formula (I)的某些取代的反转吲哚基螺[2.2]戊烷-碳腈衍生物及其药学上可接受的盐，其中R1、R2、R3、X、Y和Z如本文所定义，这些衍生物是LRRK2激酶的有效抑制剂，可能在治疗或预防LRRK2激酶参与的疾病中有用，如帕金森病和本文所述的其他疾病和疾病。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗LRRK-2激酶参与的这些疾病中使用这些化合物和组合物。

  公开号：

  WO2019074809A1
• 作为产物：
  描述：

  4,6-二氯嘧啶 、 N-Boc-4-碘哌啶 在 tris(dibenzylideneacetone)dipalladium (0) 1,2-二溴乙烷 、 锌 、 三甲基氯硅烷 作用下， 以 四氢呋喃 为溶剂， 生成 tert-butyl 4-(6-chloropyrimidin-4-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Potent heteroarylpiperidine and carboxyphenylpiperidine 1-alkyl-cyclopentane carboxamide CCR2 antagonists

  摘要：

  This report describes replacement of the 4-(4-fluorophenyl)piperidine moiety in our CCR2 antagonists with 4-heteroaryl piperidine and 4-(carboxyphenyl)-piperidine subunits. Some of the resulting analogs retained potency in our CCR2 binding assay and had improved selectivity versus the I-Kr channel; poor selectivity against I-Kr had been a liability of earlier analogs in this series. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.12.029

文献信息

• Indazolyl-spiro[2.2]pentane-carbonitrile derivatives as LRRK2 inhibitors, pharmaceutical compositions, and uses thereof
  申请人：Merck Sharp & Dohme Corp.

  公开号：US11161854B2

  公开（公告）日：2021-11-02

  The present invention is directed to substituted certain reversed indazolyl-spiro[2.2]pentane-carbonitrile derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, X, Y, and Z are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.

  本发明涉及式(I)的取代的某些反式吲唑基-螺[2.2]戊烷-甲腈衍生物：及其药学上可接受的盐，其中R1、R2、R3、X、Y和Z如本文所定义，它们是LRRK2激酶的强效抑制剂，可用于治疗或预防LRRK2激酶参与的疾病，如帕金森病和本文所述的其他疾病和失调。本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在预防或治疗涉及LRRK-2激酶的此类疾病中的用途。
• INDAZOLYL-SPIRO[2.2]PENTANE-CARBONITRILE DERIVATIVES AS LRRK2 INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP3694330A1

  公开（公告）日：2020-08-19
• [EN] INDAZOLYL-SPIRO[2.2]PENTANE-CARBONITRILE DERIVATIVES AS LRRK2 INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF<br/>[FR] DÉRIVÉS D'INDAZOLYL-SPIRO [2.2] PENTANE-CARBONITRILE EN TANT QU'INHIBITEURS DE LRRK2, COMPOSITIONS PHARMACEUTIQUES ET LEURS UTILISATIONS
  申请人：MERCK SHARP & DOHME

  公开号：WO2019074809A1

  公开（公告）日：2019-04-18

  The present invention is directed to substituted certain reversed indazolyl-spiro[2.2]pentane-carbonitrile derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, X, Y, and Z are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.

  本发明涉及Formula (I)的某些取代的反转吲哚基螺[2.2]戊烷-碳腈衍生物及其药学上可接受的盐，其中R1、R2、R3、X、Y和Z如本文所定义，这些衍生物是LRRK2激酶的有效抑制剂，可能在治疗或预防LRRK2激酶参与的疾病中有用，如帕金森病和本文所述的其他疾病和疾病。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗LRRK-2激酶参与的这些疾病中使用这些化合物和组合物。
• Potent heteroarylpiperidine and carboxyphenylpiperidine 1-alkyl-cyclopentane carboxamide CCR2 antagonists
  作者：Alexander Pasternak、Stephen D. Goble、Pasquale P. Vicario、Jerry Di Salvo、Julia M. Ayala、Mary Struthers、Julie A. DeMartino、Sander G. Mills、Lihu Yang

  DOI：10.1016/j.bmcl.2007.12.029

  日期：2008.2

  This report describes replacement of the 4-(4-fluorophenyl)piperidine moiety in our CCR2 antagonists with 4-heteroaryl piperidine and 4-(carboxyphenyl)-piperidine subunits. Some of the resulting analogs retained potency in our CCR2 binding assay and had improved selectivity versus the I-Kr channel; poor selectivity against I-Kr had been a liability of earlier analogs in this series. (C) 2007 Elsevier Ltd. All rights reserved.