4-phenylaminomethyl-piperidine-1-carboxylic acid tert-butyl ester | 199105-10-7

• 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-phenylaminomethyl-piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: N-phenyl-1-(1,1-dimethylethoxycarbonyl)piperidine-4-methylamine；Tert-butyl 4-((phenylamino)methyl)piperidine-1-carboxylate；tert-butyl 4-(anilinomethyl)piperidine-1-carboxylate
• CAS: 199105-10-7
• 化学式: C₁₇H₂₆N₂O₂
• 分子量: 290.406
• InChiKey: UJNUVGMUAYIWHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-phenylaminomethyl-piperidine-1-carboxylic acid tert-butyl ester 在 吡啶 、 盐酸 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Serine derived NK1 antagonists 2: a pharmacophore model for arylsulfonamide binding

  摘要：

  Modifications to the spirocyclic aryl sulfonamide portion of serine derived NK, antagonists allow a partial pharmacophore model to be developed. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00319-9
• 作为产物：
  描述：

  1-Boc-4-哌啶甲酸 在 硼烷四氢呋喃络合物 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 4-phenylaminomethyl-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Serine derived NK1 antagonists 2: a pharmacophore model for arylsulfonamide binding

  摘要：

  Modifications to the spirocyclic aryl sulfonamide portion of serine derived NK, antagonists allow a partial pharmacophore model to be developed. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00319-9

文献信息

• 2-aryl indole derivatives and their use as therapeutic agents
  申请人：——

  公开号：US20010039286A1

  公开（公告）日：2001-11-08

  The present invention relates compounds of the formula (I): 1 wherein R 1a , R 1b ; and R 2 represent a variety of substituents; R 3 represents an optionally substituted phenyl, biphenyl or naphthyl or heteroaryl group; R 4 represents hydrogen, C 1-6 alkyl, carbonyl (=O), (CH 2 ) p phenyl or a C 1-2 alkylene bridge across the piperidine ring; R 5 and R 6 each independently represent a variety of substituents; or R 5 and R 6 together are linked so as to form an optionally substituted 5-or 6-membered ring; X represents an oxygen or a sulfur atom, two hydrogen atoms, ═NH or ═N(C 1-6 alkyl); Y is a straight or branched C 1-4 alkylene, C 2-4 alkenylene or C 2-4 alkynylene chain; the dotted line represents an optional double bond; m is zero or an integer from 1 to 4; n is an integer from 1 to 4; and p is an integer from 1 to 4; or a pharmaceutically acceptable salt thereof. The compounds are of particular use in the treatment or prevention of depression, anxiety, pain, inflammation, migaine, emesis or postherpetic neuralgia.

  本发明涉及以下式（I）的化合物： 1 其中 R 1a ，R 1b ; 和 R 2 代表各种取代基; R 3 代表可选择地取代的苯基、联苯基或萘基或杂环芳基; R 4 代表氢、C 1-6 烷基、羰基（=O）、（CH 2 ） p 苯基或穿过哌啶环的 C 1-2 烷基桥; R 5 和 R 6 各自独立地代表各种取代基; 或 R 5 和 R 6 一起连接以形成可选择地取代的5-或6-成员环; X代表氧或硫原子、两个氢原子、═NH或═N(C 1-6 烷基); Y是直链或支链C 1-4 烷基、C 2-4 烯基或C 2-4 炔基链; 虚线表示可选的双键; m为零或1至4的整数; n为1至4的整数; p为1至4的整数; 或其药学上可接受的盐。 这些化合物在治疗或预防抑郁症、焦虑、疼痛、炎症、偏头痛、呕吐或带状疱疹后神经痛方面特别有用。
• Discovery of a Potent, Selective, and Cell-Active Dual Inhibitor of Protein Arginine Methyltransferase 4 and Protein Arginine Methyltransferase 6
  作者：Yudao Shen、Magdalena M. Szewczyk、Mohammad S. Eram、David Smil、H. Ümit Kaniskan、Renato Ferreira de Freitas、Guillermo Senisterra、Fengling Li、Matthieu Schapira、Peter J. Brown、Cheryl H. Arrowsmith、Dalia Barsyte-Lovejoy、Jing Liu、Masoud Vedadi、Jian Jin

  DOI：10.1021/acs.jmedchem.6b01033

  日期：2016.10.13

  Well-characterized selective inhibitors of protein arginine methyltransferases (PRMTs) are invaluable chemical tools for testing biological and therapeutic hypotheses. Based on 4, a fragment-like inhibitor of type I PRMTs, we conducted structure–activity relationship (SAR) studies and explored three regions of this scaffold. The studies led to the discovery of a potent, selective, and cell-active dual

  蛋白质精氨酸甲基转移酶（PRMT）的特征明确的选择性抑制剂是测试生物学和治疗假设的宝贵化学工具。基于4，一种I型PRMTs的片段样抑制剂，我们进行了结构-活性关系（SAR）研究，并探索了该支架的三个区域。导致了有效的，选择性的发现的研究，并PRMT4和PRMT6，细胞活性双重抑制剂17（MS049）。与4相比，17在生化和细胞分析中显示PRMT4和PRMT6的效力大大提高。它对PRMT4和PRMT6的选择性高于其他PRMT和其他广泛的表观遗传修饰子和非表观遗传靶标。我们还开发了46（MS049N），在生化和细胞分析中不起作用，作为化学生物学研究的阴性对照。考虑到PRMTs可能重叠的底物特异性，17和46是用于解剖特定的生物学功能以及PRMT4和PRMT6在健康和疾病中异常调节的有价值的化学工具。
• N-ARYL-N-PIPERIDIN-4-YLMETHYL-AMIDE DERIVATIVES AND THIER USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS
  申请人：Peters Dan

  公开号：US20100298380A1

  公开（公告）日：2010-11-25

  This invention relates to novel N-aryl-N-piperidin-4-ylmethyl amide derivatives useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy, and to pharmaceutical compositions comprising the compounds of the invention.

  本发明涉及一种新颖的N-芳基-N-哌啶-4-基甲酰胺衍生物，其可用作单胺神经递质再摄取抑制剂。在其他方面，本发明涉及使用这些化合物进行治疗的方法，以及包含本发明化合物的制药组合物。
• Serine derivatives and their use as therapeutic agents
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US05885999A1

  公开（公告）日：1999-03-23

  The present invention relates to compounds of formula (I): ##STR1## wherein m is zero, 1 or 2; and n is zero or 1, with the proviso that the sum total of m+n is 1 or 2; R.sup.1 represents phenyl; naphthyl; benzhydryl; or benzyl, where the naphthyl group or any phenyl moiety may be substituted; R.sup.2 represents hydrogen; phenyl; heteroaryl selected from indazolyl, thienyl, furanyl, pyridyl, thiazolyl, tetrazolyl and quinolinyl; naphthyl; benzhydryl; or benzyl; wherein each heteroaryl, the naphthyl group and any phenyl moiety may be substituted; R.sup.3 and R.sup.4 each independently represents hydrogen or C.sub.1-6 alkyl or R.sup.3 and R.sup.4 together are linked so as to form a C.sub.1-3 alkylene chain; Q represents CR.sup.5 R.sup.6 or NR.sup.5 ; X and Y each independently represents hydrogen, or together form a group .dbd.O; and Z represents a bond, O, S, SO, SO.sub.2, NR.sup.c or --(CR.sup.c R.sup.d)--, where R.sup.c and R.sup.d each independently represent hydrogen or C.sub.1-6 alkyl; or a pharmaceutically acceptable salt thereof. The compounds are of particular use in the treatment or prevention of pain, inflammation, migraine, emesis and postherpetic neuralgia.

  本发明涉及式（I）的化合物：##STR1## 其中，m为零，1或2；n为零或1，但须满足m+n的总和为1或2；R.sup.1代表苯基；萘基；苯基甲基；或苄基，其中萘基或任何苯基基团可以被取代；R.sup.2代表氢；苯基；从吲唑基、噻吩基、呋喃基、吡啶基、噻唑基、四唑基和喹啉基中选择的杂环基；萘基；苯基甲基；或苄基；其中每个杂环基、萘基和任何苯基基团可以被取代；R.sup.3和R.sup.4各自独立地代表氢或C.sub.1-6烷基，或者R.sup.3和R.sup.4一起连接形成C.sub.1-3烷基链；Q代表CR.sup.5R.sup.6或NR.sup.5；X和Y各自独立地代表氢，或者一起形成.dbd.O基团；Z代表键，O，S，SO，SO.sub.2，NR.sup.c或--(CR.sup.cR.sup.d)--，其中R.sup.c和R.sup.d各自独立地代表氢或C.sub.1-6烷基；或其药学上可接受的盐。这些化合物特别适用于治疗或预防疼痛、炎症、偏头痛、恶心和带状疱疹后神经痛。
• 1-PHENETHYLPIPERIDINE DERIVATIVES AND THEIR USE AS OPIOID RECEPTOR LIGANDS
  申请人：Peters Dan

  公开号：US20100234427A1

  公开（公告）日：2010-09-16

  This invention relates to novel 1-phenethylpiperidine derivatives useful as opioid receptor ligands. More specifically, the invention provides compounds useful as μ opioid receptor ligands. In other aspects the invention relates to the use of these compounds in a method for therapy, such as for the treatment of pain, and to pharmaceutical compositions comprising the compounds of the invention.

  本发明涉及一种新型的1-苯乙基哌啶衍生物，其可用作阿片受体配体。更具体地，本发明提供了一种有用的μ阿片受体配体化合物。在其他方面，本发明涉及使用这些化合物的治疗方法，例如用于治疗疼痛，并涉及包含本发明化合物的制药组合物。