4-(2,4-difluorophenyl)piperidine-4-carbonitrile hydrochloride | 268205-01-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(2,4-difluorophenyl)piperidine-4-carbonitrile hydrochloride
• 英文别名: 4-(2,4-Difluorophenyl)piperidine-4-carbonitrile;hydrochloride
• CAS: 268205-01-2
• 化学式: C₁₂H₁₂F₂N₂*ClH
• 分子量: 258.698
• InChiKey: XCEKCRSNKOGLHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.53
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  35.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2,4-difluorophenyl)piperidine-4-carbonitrile hydrochloride 在 硫酸 、 水 、 potassium carbonate 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 水 、 乙腈 为溶剂， 反应 4.0h， 生成 1-benzyl-4-(2,4-difluorophenyl)piperidin-4-amine
  参考文献：
  名称：

  [EN] SUBSTITUTED CYCLIC MODULATORS OF PROTEIN PHOSPHATASE 2A (PP2A) AND METHODS USING SAME
  [FR] MODULATEURS CYCLIQUES SUBSTITUÉS DE PROTÉINE PHOSPHATASE 2A (PP2A) ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  本公开涉及部分蛋白磷酸酶2A（PP2A）的化学调节剂。本公开的化合物可用于治疗、预防和/或改善癌症、糖尿病、自身免疫性疾病、固体器官移植排斥、移植物抗宿主病、慢性阻塞性肺疾病（COPD）、非酒精性脂肪性肝病、腹主动脉瘤、慢性肝病、心力衰竭、神经退行性疾病和心肌肥厚。

  公开号：

  WO2022167867A1
• 作为产物：
  描述：

  2,4-二氟苯乙腈 在 盐酸 、 sodium hydride 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.17h， 生成 4-(2,4-difluorophenyl)piperidine-4-carbonitrile hydrochloride
  参考文献：
  名称：

  In Vitro and in Vivo Evaluation of Dihydropyrimidinone C-5 Amides as Potent and Selective α_1A Receptor Antagonists for the Treatment of Benign Prostatic Hyperplasia

  摘要：

  alpha(1) Adrenergic receptors mediate both vascular and lower urinary tract tone, and alpha(1) receptor antagonists such as terazosin (1b) are used to treat both hypertension and benign prostatic hyperplasia (BPH). Recently, three different subtypes of this receptor have been identified, with the alpha(1A) receptor being most prevalent in lower urinary tract tissue. This paper explores 4-aryldihydropyrimidinones attached to an aminopropyl-4-arylpiperidine via a C-5 amide as selective alpha(1A) receptor subtype antagonists. In receptor binding assays, these types of compounds generally display K-i values for the alpha(1a) receptor subtype <1 nM while being greater than 100-fold selective versus the alpha(1b) and alpha(1d) receptor subtypes. Many of these compounds were also evaluated in vivo and found to be more potent than terazosin in both a rat model of prostate tone and a dog model of intra-urethral pressure without significantly affecting blood pressure. While many of the compounds tested displayed poor pharmacokinetics, compound 48 was found to have adequate bioavailability (>20%) and half-life (>6 h) in both rats and dogs. Due to its selectivity for the alpha(1a) over the alpha(1d) and alpha(1d) receptors as well as its favorable pharmacokinetic profile, 48 has the potential to relieve the symptoms of BPH without eliciting effects on the cardiovascular system.

  DOI：

  10.1021/jm990612y

文献信息

• Selective α1a adrenergic receptor antagonists based on 4-aryl-3,4-dihydropyridine-2-ones
  作者：Philippe G Nantermet、James C Barrow、Harold G Selnick、Carl F Homnick、Roger M Freidinger、Raymond S.L Chang、Stacey S O'Malley、Duane R Reiss、Theodore P Broten、Richard W Ransom、Douglas J Pettibone、Timothy Olah、Carlos Forray

  DOI：10.1016/s0960-894x(99)00696-4

  日期：2000.8

  A series of alpha(1a) receptor antagonists derived from a 4-aryl-3,4-dihydropyridine-2-one heterocycle is disclosed. Potency in the low nanomolar to picomolar range along with high selectivity was obtained. In vivo efficacy in a prostate contraction model in rats was observed with a few derivatives. (C) 2000 Elsevier Science Ltd. All rights reserved.
• US6228870B1
  申请人：——

  公开号：US6228870B1

  公开（公告）日：2001-05-08
• US6319932B1
  申请人：——

  公开号：US6319932B1

  公开（公告）日：2001-11-20
• [EN] OXAZOLIDINONES USEFUL AS ALPHA 1A ADRENOCEPTOR ANTAGONISTS<br/>[FR] OXAZOLIDINONES UTILES EN TANT QU'ANTAGONISTES DU RECEPTEUR ALPHA 1A ADRENERGIQUE
  申请人：MERCK & CO INC

  公开号：WO2000027817A1

  公开（公告）日：2000-05-18

  Novel hydroxymethyl- and alkoxymethyl-oxazolidinone compounds and pharmaceutically acceptable salts thereof are disclosed. The synthesis of these compounds and their use as alpha 1a adrenergic receptor antagonists is also described. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered uring flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia can be achieved.
• In Vitro and in Vivo Evaluation of Dihydropyrimidinone C-5 Amides as Potent and Selective α_1A Receptor Antagonists for the Treatment of Benign Prostatic Hyperplasia
  作者：James C. Barrow、Philippe G. Nantermet、Harold G. Selnick、Kristen L. Glass、Kenneth E. Rittle、Kevin F. Gilbert、Thomas G. Steele、Carl F. Homnick、Roger M. Freidinger、Rick W. Ransom、Paul Kling、Duane Reiss、Theodore P. Broten、Terry W. Schorn、Raymond S. L. Chang、Stacey S. O'Malley、Timothy V. Olah、Joan D. Ellis、Andrea Barrish、Kelem Kassahun、Paula Leppert、Dhanapalan Nagarathnam、Carlos Forray

  DOI：10.1021/jm990612y

  日期：2000.7.1

  alpha(1) Adrenergic receptors mediate both vascular and lower urinary tract tone, and alpha(1) receptor antagonists such as terazosin (1b) are used to treat both hypertension and benign prostatic hyperplasia (BPH). Recently, three different subtypes of this receptor have been identified, with the alpha(1A) receptor being most prevalent in lower urinary tract tissue. This paper explores 4-aryldihydropyrimidinones attached to an aminopropyl-4-arylpiperidine via a C-5 amide as selective alpha(1A) receptor subtype antagonists. In receptor binding assays, these types of compounds generally display K-i values for the alpha(1a) receptor subtype <1 nM while being greater than 100-fold selective versus the alpha(1b) and alpha(1d) receptor subtypes. Many of these compounds were also evaluated in vivo and found to be more potent than terazosin in both a rat model of prostate tone and a dog model of intra-urethral pressure without significantly affecting blood pressure. While many of the compounds tested displayed poor pharmacokinetics, compound 48 was found to have adequate bioavailability (>20%) and half-life (>6 h) in both rats and dogs. Due to its selectivity for the alpha(1a) over the alpha(1d) and alpha(1d) receptors as well as its favorable pharmacokinetic profile, 48 has the potential to relieve the symptoms of BPH without eliciting effects on the cardiovascular system.