N-((1s,4s)-4-(5-fluoro-2-(4'-formylbiphenyl-3-yloxy)nicotinamido)cyclohexyl)-2-methylthiazole-4-carboxamide | 1197291-17-0

• 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: N-((1s,4s)-4-(5-fluoro-2-(4'-formylbiphenyl-3-yloxy)nicotinamido)cyclohexyl)-2-methylthiazole-4-carboxamide
• CAS: 1197291-17-0
• 化学式: C₃₀H₂₇FN₄O₄S
• 分子量: 558.633
• InChiKey: YXFBFAOAEVHCMG-PSWAGMNNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.73
• 重原子数：
  40.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  110.28
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  N-((1s,4s)-4-(5-fluoro-2-(4'-formylbiphenyl-3-yloxy)nicotinamido)cyclohexyl)-2-methylthiazole-4-carboxamide 、 三氟乙酸 、 2,6-dimethylpiperazine 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 3.0h， 以50%的产率得到N-((1s,4s)-4-(2-(4'-(((3S,5R)-3,5-dimethylpiperazin-1-yl)methyl)biphenyl-3-yloxy)-5-fluoronicotinamido)cyclohexyl)-2-methylthiazole-4-carboxamide 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 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-(5-fluoro-2-(4'-formylbiphenyl-3-yloxy)nicotinamido)cyclohexyl)-2-methylthiazole-4-carboxamide
  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