2-chloro-4-(5-cyclopentyl-3-oxopyrazolidin-1-yl)benzonitrile | 1242145-40-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 2-chloro-4-(5-cyclopentyl-3-oxopyrazolidin-1-yl)benzonitrile
• CAS: 1242145-40-9
• 化学式: C₁₅H₁₆ClN₃O
• 分子量: 289.765
• InChiKey: HCIUAOGRLBWDMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 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：
  56.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-4-(5-cyclopentyl-3-oxopyrazolidin-1-yl)benzonitrile 在 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 2.5h， 以88.9%的产率得到(+/-)-2-chloro-4-(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
• 作为产物：
  描述：

  2-chloro-4-hydrazinobenzonitrile hydrochloride 、 ethyl 3-cyclopentyl acrylate 在 sodium ethanolate 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以52.3%的产率得到2-chloro-4-(5-cyclopentyl-3-oxopyrazolidin-1-yl)benzonitrile
  参考文献：
  名称：

  [EN] 4, 5-DIHYDRO-1H-PYRAZOLE COMPOUNDS AND THEIR PHARMACEUTICAL USES
  [FR] COMPOSÉS 4,5-DIHYDRO-LH-PYRAZOLE ET LEURS UTILISATIONS PHARMACEUTIQUES

  摘要：

  公开号：

  WO2010116282A8

文献信息

• 4,5-DIHYDRO-1H-PYRAZOLE COMPOUNDS AND THEIR PHARMACEUTICAL USES
  申请人：Arhancet Graciela Barbieri

  公开号：US20120022058A1

  公开（公告）日：2012-01-26

  Mineralocorticoid receptor antagonists (MRa), pharmaceutical compositions containing such inhibitors and the use of such inhibitors to treat, for example, diabetic nephropathy and hypertension in mammals, including humans.

  矿物质皮质激素受体拮抗剂（MRa），含有这种抑制剂的制药组合物以及使用这种抑制剂治疗哺乳动物（包括人类）中的糖尿病肾病和高血压。