3-(3'-((3-(((1s,4s)-4-(1,5-dimethyl-1H-pyrazole-3-carboxamido)cyclohexyl)carbamoyl)-5-fluoropyridin-2-yl)oxy)-[1,1'-biphenyl]-4-yl)propyl methanesulfonate | 1197291-38-5

• 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: 3-(3'-((3-(((1s,4s)-4-(1,5-dimethyl-1H-pyrazole-3-carboxamido)cyclohexyl)carbamoyl)-5-fluoropyridin-2-yl)oxy)-[1,1'-biphenyl]-4-yl)propyl methanesulfonate
• CAS: 1197291-38-5
• 化学式: C₃₄H₃₈FN₅O₆S
• 分子量: 663.77
• InChiKey: KPHRFHUAFFMRFB-HNRBIFIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  47.0
• 可旋转键数：
  12.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  141.51
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  3-(3'-((3-(((1s,4s)-4-(1,5-dimethyl-1H-pyrazole-3-carboxamido)cyclohexyl)carbamoyl)-5-fluoropyridin-2-yl)oxy)-[1,1'-biphenyl]-4-yl)propyl methanesulfonate 、 三氟乙酸 、 2,6-dimethylpiperazine 以 乙腈 为溶剂， 反应 0.5h， 以43%的产率得到N-((1s,4s)-4-(1,5-dimethyl-1H-pyrazole-3-carboxamido)cyclohexyl)-2-(4'-(3-((3S,5R)-3,5-dimethylpiperazin-1-yl)propyl)biphenyl-3-yloxy)-5-fluoronicotinamide trifluoroacetic acid salt
  参考文献：
  名称：

  Efficacious Inhaled PDE4 Inhibitors with Low Emetic Potential and Long Duration of Action for the Treatment of COPD

  摘要：

  Oral phosphodiesterase 4 (PDE4) inhibitors, such as cilomilast and roflumilast, have been shown to be efficacious against chronic obstructive pulmonary disease (COPD). However, these drugs have been hampered by mechanism-related side effects such as nausea and emesis at high doses. Compounds administered by inhalation are delivered directly to the site of action and may improve the therapeutic index required to overcome side effects. This paper describes systematic and rational lead optimization to deliver highly potent, long-acting, and efficacious preclinical inhaled PDE4 inhibitors with low emetic potential.

  DOI：

  10.1021/jm5001216
• 作为产物：
  描述：

  N-((1s,4s)-4-aminocyclohexyl)-5-fluoro-2-(3-iodophenoxy)nicotinamide hydrochloride 在 吡啶 、 四(三苯基膦)钯 、 sodium carbonate 、 1-丙基磷酸酐 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 38.0h， 生成 3-(3'-((3-(((1s,4s)-4-(1,5-dimethyl-1H-pyrazole-3-carboxamido)cyclohexyl)carbamoyl)-5-fluoropyridin-2-yl)oxy)-[1,1'-biphenyl]-4-yl)propyl methanesulfonate
  参考文献：
  名称：

  Efficacious Inhaled PDE4 Inhibitors with Low Emetic Potential and Long Duration of Action for the Treatment of COPD

  摘要：

  Oral phosphodiesterase 4 (PDE4) inhibitors, such as cilomilast and roflumilast, have been shown to be efficacious against chronic obstructive pulmonary disease (COPD). However, these drugs have been hampered by mechanism-related side effects such as nausea and emesis at high doses. Compounds administered by inhalation are delivered directly to the site of action and may improve the therapeutic index required to overcome side effects. This paper describes systematic and rational lead optimization to deliver highly potent, long-acting, and efficacious preclinical inhaled PDE4 inhibitors with low emetic potential.

  DOI：

  10.1021/jm5001216