(+/-)-4-[1-(4-cyanophenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]-N-[2-(dimethylamino)ethyl]-N-methylbenzamide | 1242144-81-5

• 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: (+/-)-4-[1-(4-cyanophenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]-N-[2-(dimethylamino)ethyl]-N-methylbenzamide
• 英文别名: 4-[2-(4-cyanophenyl)-3-(4-fluorophenyl)-3,4-dihydropyrazol-5-yl]-N-[2-(dimethylamino)ethyl]-N-methylbenzamide
• CAS: 1242144-81-5
• 化学式: C₂₈H₂₈FN₅O
• 分子量: 469.562
• InChiKey: HKUKEMRCCWWBFD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  62.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+/-)-4-[1-(4-cyanophenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]-N-[2-(dimethylamino)ethyl]-N-methylbenzamide 、 三氟乙酸 以 水 、 乙腈 为溶剂， 生成 (+/-)-4-[1-(4-cyanophenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]-N-[2-(dimethylamino)ethyl]-N-methylbenzamide trifluoroacetate
  参考文献：
  名称：

  Discovery of (3S,3aR)-2-(3-Chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic Acid (PF-3882845), an Orally Efficacious Mineralocorticoid Receptor (MR) Antagonist for Hypertension and Nephropathy

  摘要：

  We have discovered a novel class of nonsteroidal pyrazoline antagonists of the mineralocorticoid receptor (M R) that show excellent potency and selectivity against other nuclear receptors. Early analogues were poorly soluble and had a propensity to inhibit the hERG channel. Remarkably, both of these challenges were overcome by incorporation of a single carboxylate moiety. Structural modification of carboxylate-containing lead R-4g with a wide range of substituents at each position of the pyrazoline ring resulted in R-12o, which shows excellent activity against MR and reasonable pharmacokinetic profile. Introduction of conformational restriction led to a novel series characterized by exquisite potency and favorable steroid receptor selectivity and pharmacokinetic profile. Oral dosing of 3S,3aR-27d (PF-3882845) in the Dahl salt sensitive preclinical model of salt-induced hypertension and nephropathy showed blood pressure attenuation significantly greater than that with eplerenone, reduction in urinary albumin, and renal protection. As a result of these findings, 3S,3aR-27d was advanced to clinical studies.

  DOI：

  10.1021/jm100505n
• 作为产物：
  描述：

  (+/-)-4-[1-(4-cyanophenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]benzoic acid 、 N,N,N'-三甲基乙二胺 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 以23%的产率得到(+/-)-4-[1-(4-cyanophenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]-N-[2-(dimethylamino)ethyl]-N-methylbenzamide
  参考文献：
  名称：

  Discovery of (3S,3aR)-2-(3-Chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic Acid (PF-3882845), an Orally Efficacious Mineralocorticoid Receptor (MR) Antagonist for Hypertension and Nephropathy

  摘要：

  We have discovered a novel class of nonsteroidal pyrazoline antagonists of the mineralocorticoid receptor (M R) that show excellent potency and selectivity against other nuclear receptors. Early analogues were poorly soluble and had a propensity to inhibit the hERG channel. Remarkably, both of these challenges were overcome by incorporation of a single carboxylate moiety. Structural modification of carboxylate-containing lead R-4g with a wide range of substituents at each position of the pyrazoline ring resulted in R-12o, which shows excellent activity against MR and reasonable pharmacokinetic profile. Introduction of conformational restriction led to a novel series characterized by exquisite potency and favorable steroid receptor selectivity and pharmacokinetic profile. Oral dosing of 3S,3aR-27d (PF-3882845) in the Dahl salt sensitive preclinical model of salt-induced hypertension and nephropathy showed blood pressure attenuation significantly greater than that with eplerenone, reduction in urinary albumin, and renal protection. As a result of these findings, 3S,3aR-27d was advanced to clinical studies.

  DOI：

  10.1021/jm100505n