N-((1s,4s)-4-aminocyclohexyl)-5-fluoro-2-(3-iodophenoxy)nicotinamide hydrochloride | 1197013-81-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-((1s,4s)-4-aminocyclohexyl)-5-fluoro-2-(3-iodophenoxy)nicotinamide hydrochloride
• CAS: 1197013-81-2
• 化学式: C₁₈H₁₉FIN₃O₂*ClH
• 分子量: 491.732
• InChiKey: CISABISMHXSFAN-KAECKJJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.04
• 重原子数：
  26.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  77.24
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-((1s,4s)-4-aminocyclohexyl)-5-fluoro-2-(3-iodophenoxy)nicotinamide hydrochloride 在 2-双环己基膦-2',6'-二甲氧基联苯 、 palladium diacetate 、 potassium carbonate 、 1-丙基磷酸酐 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 23.0h， 生成 N-((1s,4s)-4-(1,5-dimethyl-1H-pyrazole-3-carboxamido)cyclohexyl)-5-fluoro-2-(4'-hydroxy-2'-(morpholinomethyl)biphenyl-3-yloxy)nicotinamide
  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：

  tert-butyl N-[(1s,4s)-4-(2-chloro-5-fluoronicotinamido)cyclohexyl]carbamate 在 盐酸 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.0h， 生成 N-((1s,4s)-4-aminocyclohexyl)-5-fluoro-2-(3-iodophenoxy)nicotinamide hydrochloride
  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