2-chloro-4-[(5R)-3-chloro-5-cyclopentyl-4,5-dihydro-1H-pyrazol-1-yl]benzonitrile | 1242145-41-0

• 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-[(5R)-3-chloro-5-cyclopentyl-4,5-dihydro-1H-pyrazol-1-yl]benzonitrile
• 英文别名: (R)-2-chloro-4-(3-chloro-5-cyclopentyl-4,5-dihydro-1H-pyrazol-1-yl)benzonitrile；2-chloro-4-[(3R)-5-chloro-3-cyclopentyl-3,4-dihydropyrazol-2-yl]benzonitrile
• CAS: 1242145-41-0
• 化学式: C₁₅H₁₅Cl₂N₃
• 分子量: 308.21
• InChiKey: PYQCYQHGOBMXJY-CQSZACIVSA-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

• 作为反应物：
  描述：

  4-羧基-3-氟苯硼酸 、 2-chloro-4-[(5R)-3-chloro-5-cyclopentyl-4,5-dihydro-1H-pyrazol-1-yl]benzonitrile 在 四(三苯基膦)钯 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 以85%的产率得到4-[(5R)-1-(3-chloro-4-cyanophenyl)-5-cyclopentyl-4,5-dihydro-1H-pyrazol-3-yl]-2-fluorobenzoic acid
  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-(3-chloro-5-cyclopentyl-4,5-dihydro-1H-pyrazol-1-yl)benzonitrile 在 chiral SFC Column: AD-H 50 x 250 mm 作用下， 以 甲醇 、 二氧化碳 为溶剂， 生成 2-chloro-4-[(5R)-3-chloro-5-cyclopentyl-4,5-dihydro-1H-pyrazol-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。
• 4, 5-DIHYDRO-1H-PYRAZOLE COMPOUNDS AND THEIR PHARMACEUTICAL USES
  申请人：Pfizer Inc.

  公开号：EP2417121A1

  公开（公告）日：2012-02-15
• [EN] 4, 5-DIHYDRO-LH-PYRAZOLE COMPOUNDS AND THEIR PHARMACEUTICAL USES<br/>[FR] COMPOSÉS 4,5-DIHYDRO-LH-PYRAZOLE ET LEURS UTILISATIONS PHARMACEUTIQUES
  申请人：PFIZER

  公开号：WO2010116282A1

  公开（公告）日：2010-10-14

  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.
• [EN] SPIRO-CONTAINING DIHYDROPYRAZOLE COMPOUNDS<br/>[FR] COMPOSÉS DIHYDROPYRAZOLES CONTENANT LE SPIRO
  申请人：KBP BIOSCIENCES CO LTD

  公开号：WO2012126275A1

  公开（公告）日：2012-09-27

  Provided are compounds of formula (I), pharmaceutically acceptable salts, esters, or solvates, or prodrugs or isomers thereof. Thereinto, Cy1, L, X, Y1, Y2, n1, n2, n3, n4, R1a, R1b, R3a, R3b, R4, R5 and m are defined as in the description.