2-chloro-4-[(5S)-3-chloro-5-cyclopentyl-4,5-dihydro-1H-pyrazol-1-yl]benzonitrile | 1248593-38-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 2-chloro-4-[(5S)-3-chloro-5-cyclopentyl-4,5-dihydro-1H-pyrazol-1-yl]benzonitrile
• 英文别名: (S)-2-chloro-4-(3-chloro-5-cyclopentyl-4,5-dihydro-1H-pyrazol-1-yl)benzonitrile；2-chloro-4-[(3S)-5-chloro-3-cyclopentyl-3,4-dihydropyrazol-2-yl]benzonitrile
• CAS: 1248593-38-5
• 化学式: C₁₅H₁₅Cl₂N₃
• 分子量: 308.21
• InChiKey: PYQCYQHGOBMXJY-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  39.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (+/-)-2-chloro-4-(3-chloro-5-cyclopentyl-4,5-dihydro-1H-pyrazol-1-yl)benzonitrile 在 Chiralpak AD-H 作用下， 以 甲醇 、 二氧化碳 为溶剂， 以43%的产率得到2-chloro-4-[(5R)-3-chloro-5-cyclopentyl-4,5-dihydro-1H-pyrazol-1-yl]benzonitrile
  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