4-(6-Methylpyridin-2-yl)piperidine-4-carbonitrile | 866585-43-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(6-Methylpyridin-2-yl)piperidine-4-carbonitrile
• CAS: 866585-43-5
• 化学式: C₁₂H₁₅N₃
• 分子量: 201.271
• InChiKey: HOEHAMFNZLBTFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  48.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(6-Methylpyridin-2-yl)piperidine-4-carbonitrile 、 丙基磺酰氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 4-(6-methylpyridin-2-yl)-1-(propylsulfonyl)piperidine-4-carbonitrile
  参考文献：
  名称：

  Discovery of N-{[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamides as novel, selective and potent GlyT1 inhibitors

  摘要：

  Employing an iterative analogue library approach, novel potent and selective glycine transporter 1 (GlyT1) inhibitors containing a 4-pyridin-2-ylpiperidine sulfonamide have been discovered. These inhibitors are devoid of time-dependent CYP inhibition activity and exhibit improved aqueous solubility versus the corresponding 4-phenylpiperidine analogues. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.12.115
• 作为产物：
  描述：

  tert-butyl 4-cyano-4-(6-methylpyridin-2-yl)piperidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 4-(6-Methylpyridin-2-yl)piperidine-4-carbonitrile
  参考文献：
  名称：

  Discovery of N-{[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamides as novel, selective and potent GlyT1 inhibitors

  摘要：

  Employing an iterative analogue library approach, novel potent and selective glycine transporter 1 (GlyT1) inhibitors containing a 4-pyridin-2-ylpiperidine sulfonamide have been discovered. These inhibitors are devoid of time-dependent CYP inhibition activity and exhibit improved aqueous solubility versus the corresponding 4-phenylpiperidine analogues. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.12.115

文献信息

• Heteroaryl Piperidine Glycine Transporter Inhibitors
  申请人：Blackaby Wesley

  公开号：US20070254880A1

  公开（公告）日：2007-11-01

  The present invention is directed to pyridyl, pyridazinyl, pyrimidinyl and pyrazinyl piperidine compounds that inhibit the glycine transporter GlyT1 and which are useful in the treatment of neurological and psychiatric disorders associated with glycinergic or glutamatergic neurotransmission dysfunction and diseases in which the glycine transporter GlyT1 is involved.

  本发明涉及抑制甘氨酸转运蛋白GlyT1的吡啶基、吡啶并嗪基、嘧啶基和吡嗪基哌啶化合物，这些化合物在治疗与甘氨酸或谷氨酸神经传递功能障碍相关的神经系统和精神疾病以及涉及甘氨酸转运蛋白GlyT1的疾病中具有用途。
• Discovery of a Selective Allosteric M₁ Receptor Modulator with Suitable Development Properties Based on a Quinolizidinone Carboxylic Acid Scaffold
  作者：Scott D. Kuduk、Ronald K. Chang、Christina N. Di Marco、Daniel R. Pitts、Thomas J. Greshock、Lei Ma、Marion Wittmann、Matthew A. Seager、Kenneth A. Koeplinger、Charles D. Thompson、George D. Hartman、Mark T. Bilodeau、William J. Ray

  DOI：10.1021/jm200400m

  日期：2011.7.14

  One approach to ameliorate the cognitive decline in Alzheimer's disease (AD) has been to restore neuronal signaling from the basal forebrain cholinergic system via the activation of the M-1 muscarinic receptor. A number of nonselective M-1 muscarinic agonists have previously shown positive effects on cognitive behaviors in AD patients, but were limited due to cholinergic adverse events thought to be mediated by the activation of the M-2 to M-5 subtypes. One strategy to confer selectivity for M-1 is the identification of positive allosteric modulators, which would target an allosteric site on the M-1 receptor rather than the highly conserved orthosteric acetylcholine binding site. Quinoline carboxylic acids have I been previously identified as highly selective M-1 positive allosteric modulators with good pharmacokinetic and in vivo properties. Herein is described the optimization of a novel quinolizidinone carboxylic acid scaffold with 4-cyanopiperidines being a key discovery in terms of enhanced activity. In particular, modulator 4i gave high plasma free fractions, enhanced central nervous system (CNS) exposure, was efficacious in a rodent in vivo model of cognition, and afforded good physicochemical properties suitable for further preclinical evaluation.
• Discovery of Naphthyl-Fused 5-Membered Lactams as a New Class of M₁ Positive Allosteric Modulators
  作者：Zhi-Qiang Yang、Youheng Shu、Lei Ma、Marion Wittmann、William J. Ray、Matthew A. Seager、Kenneth A. Koeplinger、Charles D. Thompson、George D. Hartman、Mark T. Bilodeau、Scott D. Kuduk

  DOI：10.1021/ml500055h

  日期：2014.5.8

  Selective activation of the M-1 muscarinic receptor via positive allosteric modulation represents an original approach to treat the cognitive decline in patients with Alzheimer's disease. A series of naphthyl-fused 5-membered lactams were identified as a new class of M-1 positive allosteric modulators and were found to possess good potency and in vivo efficacy.
• HETEROARYL PIPERIDINE GLYCINE TRANSPORTER INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1729772B1

  公开（公告）日：2016-12-07
• US7825135B2
  申请人：——

  公开号：US7825135B2

  公开（公告）日：2010-11-02