(+/-)-2-chloro-4-(3-chloro-5-cyclopentyl-4,5-dihydro-1H-pyrazol-1-yl)benzonitrile | 1242145-42-1

• 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-(3-chloro-5-cyclopentyl-4,5-dihydro-1H-pyrazol-1-yl)benzonitrile
• 英文别名: 2-chloro-4-(3-chloro-5-cyclopentyl-4,5-dihydro-1H-pyrazole-1-yl)benzonitrile；2-chloro-4-(5-chloro-3-cyclopentyl-3,4-dihydropyrazol-2-yl)benzonitrile
• CAS: 1242145-42-1
• 化学式: C₁₅H₁₅Cl₂N₃
• 分子量: 308.21
• InChiKey: PYQCYQHGOBMXJY-UHFFFAOYSA-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：

  (+/-)-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
• 作为产物：
  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

文献信息

• Fused Ring Compound For Use As Mineralocorticoid Receptor Antagonist
  申请人：Huang Zhenhua

  公开号：US20130289029A1

  公开（公告）日：2013-10-31

  The present invention belongs to the technical field of medicine, relating in particular to: a fused ring compound as represented by Formula (I) for use as a mineralocorticoid receptor antagonist, a pharmaceutically acceptable salt thereof, and an isomer thereof; a preparation method for these compounds; a pharmaceutical preparation containing these compounds; and an application of these compounds, the pharmaceutically acceptable salt thereof, or the isomers thereof in the preparation of medicants for the treatment and/or prevention of kidney injury, cardiovascular diseases such as hypertension, and/or endocrine disease. The definitions of X, Y 1 , Y 2 , Y 3 , R 1 , R 2a , R 2b , R 3a , R 3b , R 4 , Cy and n are as presented in the description.

  本发明属于医学技术领域，具体涉及以下内容：一种由化学式（I）表示的融合环化合物，用作醛固酮受体拮抗剂，其药学上可接受的盐和异构体；这些化合物的制备方法；含有这些化合物的药物制剂；以及这些化合物、其药学上可接受的盐或其异构体在制备用于治疗和/或预防肾损伤、高血压等心血管疾病和/或内分泌疾病的药物时的应用。X、Y1、Y2、Y3、R1、R2a、R2b、R3a、R3b、R4、Cy和n的定义如描述中所示。
• 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。
• Fused ring compound for use as mineralocorticoid receptor antagonist
  申请人：Huang Zhenhua

  公开号：US08946279B2

  公开（公告）日：2015-02-03

  The present invention belongs to the technical field of medicine, relating in particular to: a fused ring compound as represented by Formula (I) for use as a mineralocorticoid receptor antagonist, a pharmaceutically acceptable salt thereof, and an isomer thereof; a preparation method for these compounds; a pharmaceutical preparation containing these compounds; and an application of these compounds, the pharmaceutically acceptable salt thereof, or the isomers thereof in the preparation of medicants for the treatment and/or prevention of kidney injury, cardiovascular diseases such as hypertension, and/or endocrine disease. The definitions of X, Y1, Y2, Y3, R1, R2a, R2b, R3a, R3b, R4, Cy and n are as presented in the description.

  本发明属于医学技术领域，特别涉及以下内容：一种由式（I）所代表的融合环化合物，用作矿物质皮质激素受体拮抗剂，其药学上可接受的盐和异构体；这些化合物的制备方法；含有这些化合物的制药制剂；以及这些化合物、其药学上可接受的盐或异构体在治疗和/或预防肾脏损伤、心血管疾病如高血压和/或内分泌疾病的药物制剂中的应用。其中X、Y1、Y2、Y3、R1、R2a、R2b、R3a、R3b、R4、Cy和n的定义如描述中所示。
• FUSED RING COMPOUND FOR USE AS MINERALOCORTICOID RECEPTOR ANTAGONIST
  申请人：KBP Biosciences Co., Ltd.

  公开号：EP2607363A1

  公开（公告）日：2013-06-26

  The present invention belongs to the technical field of medicine, relating in particular to: a fused ring compound as represented by Formula (I) for use as a mineralocorticoid receptor antagonist, a pharmaceutically acceptable salt thereof, and an isomer thereof; a preparation method for these compounds; a pharmaceutical preparation containing these compounds; and an application of these compounds, the pharmaceutically acceptable salt thereof, or the isomers thereof in the preparation of medicants for the treatment and/or prevention of kidney injury, cardiovascular diseases such as hypertension, and/or endocrine disease. The definitions of X, Y1, Y2, Y3, R1, R2a,R2b , R3a , R3b, R4, Cy and n are as presented in the description.

  本发明属于医药技术领域，尤其涉及：由式（I）表示的用作矿质皮质激素受体拮抗剂的融合环化合物、其药学上可接受的盐及其异构体；这些化合物的制备方法；含有这些化合物的药物制剂；以及这些化合物、其药学上可接受的盐或其异构体在制备治疗和/或预防肾损伤、高血压等心血管疾病和/或内分泌疾病的药物中的应用。X、Y1、Y2、Y3、R1、R2a、R2b、R3a、R3b、R4、Cy 和 n 的定义如描述中所示。
• 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