1-Boc-2-[(4-氟苯基氨基)-甲基]-哌啶 | 887587-99-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 1-Boc-2-[(4-氟苯基氨基)-甲基]-哌啶
• 英文名称: tert-butyl 2-((4-fluorophenylamino)methyl)piperidine-1-carboxylate
• 英文别名: Tert-butyl 2-[(4-fluoroanilino)methyl]piperidine-1-carboxylate
• CAS: 887587-99-7
• 化学式: C₁₇H₂₅FN₂O₂
• 分子量: 308.396
• InChiKey: BYTDPTQQKFPTIN-UHFFFAOYSA-N

物化性质

• 沸点：
  414.9±20.0 °C(Predicted)
• 密度：
  1.126±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-Boc-2-[(4-氟苯基氨基)-甲基]-哌啶 在 盐酸 、 sodium hydrogen sulfide 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-((5-((4-fluorophenyl)(piperidin-2-ylmethyl)carbamoyl)pyridin-2-ylthio)methyl)phenylboronic acid
  参考文献：
  名称：

  Discovery of 2-[5-(4-Fluorophenylcarbamoyl)pyridin-2-ylsulfanylmethyl]phenylboronic Acid (SX-517): Noncompetitive Boronic Acid Antagonist of CXCR1 and CXCR2

  摘要：

  The G protein-coupled chemokine receptors CXCR1 and CXCR2 play key roles in inflammatory diseases and carcinogenesis. In inflammation, they activate and recruit polymorphonuclear cells (PMNs) through binding of the chemokines CXCL1 (CXCR1) and CXCL8 (CXCR1 and CXCR2). Structure-activity studies that examined the effect of a novel series of S-substituted 6-mercapto-N-phenyl-nicotinamides on CXCL1-stimulated Ca2+ flux in whole human PMNs led to the discovery of 2-[5-(4-fluorophenylcarbamoyl)pyridin-2-ylsulfanylmethyl]phenylboronic acid (SX-517), a potent noncompetitive boronic acid CXCR1/2 antagonist. SX-517 inhibited CXCL1-induced Ca2+ flux (IC50 = 38 nM) in human PMNs but had no effect on the Ca2+ flux induced by C5a, fMLF, or PAF. In recombinant HEK293 cells that stably expressed CXCR2, SX-517 antagonized CXCL8-induced [S-35]GTP?S binding (IC50 = 60 nM) and ERK1/2 phosphorylation. Inhibition was noncompetitive, with SX-517 unable to compete the binding of [I-125]-CXCL8 to CXCR2 membranes. SX-517 (0.2 mg/kg iv) significantly inhibited inflammation in an in vivo murine model. SX-517 is the first reported boronic acid chemokine antagonist and represents a novel pharmacophore for CXCR1/2 antagonism.

  DOI：

  10.1021/jm500827t
• 作为产物：
  描述：

  2-(羟甲基)哌啶-1-甲酸叔丁酯 在 三乙酰氧基硼氢化钠 、 溶剂黄146 、 2-碘酰基苯甲酸 作用下， 以 二甲基亚砜 、 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， 生成 1-Boc-2-[(4-氟苯基氨基)-甲基]-哌啶
  参考文献：
  名称：

  PYRIDINECARBOXAMIDES AS CXCR2 MODULATORS

  摘要：

  公开号：

  EP2942346B1

文献信息

• Pyridine- and Pyrimidinecarboxamides as CXCR2 Modulators
  申请人：Maeda Dean Y.

  公开号：US20100210593A1

  公开（公告）日：2010-08-19

  There is disclosed pyridine- and pyrimidinecarboxamide compounds useful as pharmaceutical agents, synthesis processes, and pharmaceutical compositions which include pyridine- and pyrimidinecarboxamides compounds. More specifically, there is disclosed a genus of CXCR2 inhibitor compounds that are useful for treating a variety of inflammatory and neoplastic disorders.

  披露了作为药物剂的吡啶和嘧啶羧酰胺化合物，合成过程以及包括吡啶和嘧啶羧酰胺化合物的药物组合物。更具体地，披露了一类CXCR2抑制剂化合物，可用于治疗各种炎症和肿瘤性疾病。
• PYRIMIDINECARBOXAMIDES AS CXCR2 MODULATORS
  申请人：SYNTRIX BIOSYSTEMS, INC.

  公开号：US20140206647A1

  公开（公告）日：2014-07-24

  There is disclosed pyridine- and pyrimidinecarboxamide compounds useful as pharmaceutical agents, synthesis processes, and pharmaceutical compositions which include pyridine- and pyrimidinecarboxamides compounds. More specifically, there is disclosed a genus of CXCR2 inhibitor compounds that are useful for treating a variety of inflammatory and neoplastic disorders.

  本发明公开了吡啶和嘧啶羧酰胺化合物，可用作药物治疗剂，合成过程和包括吡啶和嘧啶羧酰胺化合物的制药组合物。更具体地，本发明公开了一类CXCR2抑制剂化合物，可用于治疗各种炎症和肿瘤性疾病。
• US8981106B2
  申请人：——

  公开号：US8981106B2

  公开（公告）日：2015-03-17
• Discovery of 2-[5-(4-Fluorophenylcarbamoyl)pyridin-2-ylsulfanylmethyl]phenylboronic Acid (SX-517): Noncompetitive Boronic Acid Antagonist of CXCR1 and CXCR2
  作者：Dean Y. Maeda、Angela M. Peck、Aaron D. Schuler、Mark T. Quinn、Liliya N. Kirpotina、Winston N. Wicomb、Guo-Huang Fan、John A. Zebala

  DOI：10.1021/jm500827t

  日期：2014.10.23

  The G protein-coupled chemokine receptors CXCR1 and CXCR2 play key roles in inflammatory diseases and carcinogenesis. In inflammation, they activate and recruit polymorphonuclear cells (PMNs) through binding of the chemokines CXCL1 (CXCR1) and CXCL8 (CXCR1 and CXCR2). Structure-activity studies that examined the effect of a novel series of S-substituted 6-mercapto-N-phenyl-nicotinamides on CXCL1-stimulated Ca2+ flux in whole human PMNs led to the discovery of 2-[5-(4-fluorophenylcarbamoyl)pyridin-2-ylsulfanylmethyl]phenylboronic acid (SX-517), a potent noncompetitive boronic acid CXCR1/2 antagonist. SX-517 inhibited CXCL1-induced Ca2+ flux (IC50 = 38 nM) in human PMNs but had no effect on the Ca2+ flux induced by C5a, fMLF, or PAF. In recombinant HEK293 cells that stably expressed CXCR2, SX-517 antagonized CXCL8-induced [S-35]GTP?S binding (IC50 = 60 nM) and ERK1/2 phosphorylation. Inhibition was noncompetitive, with SX-517 unable to compete the binding of [I-125]-CXCL8 to CXCR2 membranes. SX-517 (0.2 mg/kg iv) significantly inhibited inflammation in an in vivo murine model. SX-517 is the first reported boronic acid chemokine antagonist and represents a novel pharmacophore for CXCR1/2 antagonism.
• PYRIDINECARBOXAMIDES AS CXCR2 MODULATORS
  申请人：Syntrix Biosystems, Inc.

  公开号：EP2942346B1

  公开（公告）日：2020-05-06