N-((1-(4-benzylpiperazin-1-yl)cyclohexyl)methyl)-2,2,2-trifluoroacetamide | 511540-35-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-((1-(4-benzylpiperazin-1-yl)cyclohexyl)methyl)-2,2,2-trifluoroacetamide
• 英文别名: 1-[1-(trifluoroacetamidomethyl)cyclohexyl]-4-benzylpiperazine；N-[[1-(4-benzylpiperazin-1-yl)cyclohexyl]methyl]-2,2,2-trifluoroacetamide
• CAS: 511540-35-5
• 化学式: C₂₀H₂₈F₃N₃O
• 分子量: 383.457
• InChiKey: BJIOLZGPXPKUNA-UHFFFAOYSA-N

物化性质

• 沸点：
  468.3±45.0 °C(Predicted)
• 密度：
  1.191±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-((1-(4-benzylpiperazin-1-yl)cyclohexyl)methyl)-2,2,2-trifluoroacetamide 在 palladium on activated charcoal 甲酸铵 、 potassium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 {2-[(R)-2-[4-(1-Aminomethyl-cyclohexyl)-piperazin-1-yl]-1-(2,4-dichloro-benzyl)-2-oxo-ethylcarbamoyl]-ethyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Structure–activity relationship of a series of cyclohexylpiperidines bearing an amide side chain as antagonists of the human melanocortin-4 receptor

  摘要：

  A series of cyclohexylpiperazines was synthesized as potent and selective antagonists of the human MC4 receptor. Compound 14t displayed binding affinity (K-i) of 4.2 and 1100 nM at MC4R and MC3R, respectively. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.017
• 作为产物：
  描述：

  1-(4-benzylpiperazin-1-yl)cyclohexanecarbonitrile 在 sodium hydroxide 、 LiAlH4 、 三乙胺 、 三氟乙酸酐 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 N-((1-(4-benzylpiperazin-1-yl)cyclohexyl)methyl)-2,2,2-trifluoroacetamide
  参考文献：
  名称：

  Ligands of melanocortin receptors and compositions and methods related thereto

  摘要：

  具有治疗基于黑素皮质素受体的疾病的功效的化合物，其作为黑素皮质素受体配体发挥作用。这些化合物具有以下结构（I）：包括立体异构体、前药和其在药用上可接受的盐，其中A、m、n、R1、R2、R3a、R3b、R4、R5、R6W1、W2、W3、W4、Y1、Y2、Y3和Y4如本文所定义。还公开了含有结构（I）的化合物的药物组合物，以及与其使用相关的方法。

  公开号：

  US20030158209A1

文献信息

• [EN] LIGANDS OF MELANOCORTIN RECEPTORS AND COMPOSITIONS AND METHODS RELATED THERETO<br/>[FR] LIGANDS DU RECEPTEUR DE LA MELANOCORTINE ET COMPOSITIONS ET METHODES ASSOCIEES
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2005040109A1

  公开（公告）日：2005-05-06

  Compounds which function as melanocortin receptor ligands and having utility in the treatment of melanocortin receptor-based disorders. The compounds have the following structure (I): (R4)s (R 2)n N~ X1-X2 (CR1aCRlb)q 1~ N R1-lm 1 O R3 (I) including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein m, n, q, s, R1, R1a, R1b, R2, R3, R4, X1 X2 and X3 are as defined herein. Pharmaceutical compositions containing a compound of structure (I), as well as methods relating to the use thereof, are also disclosed.

  化合物作为黑色素皮质激素受体配体，并在治疗基于黑色素皮质激素受体的疾病中具有用途。这些化合物具有以下结构（I）：（R4）s（R 2）n N〜X1-X2（CR1aCRlb）q 1〜N R1-lm 1 O R3（I），包括立体异构体，前药和其药用盐，其中m、n、q、s、R1、R1a、R1b、R2、R3、R4、X1、X2和X3如本文所定义。还公开了含有结构（I）化合物的药物组合物，以及与其使用相关的方法。
• GLYCINE TRANSPORTER-1 INHIBITORS, METHODS OF MAKING THEM, AND USES THEREOF
  申请人：CIOFFI Christopher L.

  公开号：US20110312931A1

  公开（公告）日：2011-12-22

  The compounds of the present invention are represented by the following formula (I): wherein the substituents R 1 , R 2 , R 3 , R 4 , (R 5 ) m , R 6 , A, X, and Y are as defined herein. The compounds are useful in methods of treating a disorder which is created by or is dependent upon inhibiting GlyT-1.

  本发明的化合物由以下公式（I）表示：其中，取代基R1、R2、R3、R4、（R5）m、R6、A、X和Y的定义如本文所述。这些化合物可用于治疗由抑制GlyT-1引起或依赖于GlyT-1抑制的疾病的方法。
• Synthesis and Biological Evaluation of<i>N</i>-((1-(4-(Sulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide Inhibitors of Glycine Transporter-1
  作者：Christopher L. Cioffi、Shuang Liu、Mark A. Wolf、Peter R. Guzzo、Kashinath Sadalapure、Visweswaran Parthasarathy、David T. J. Loong、Jun-Ho Maeng、Edmund Carulli、Xiao Fang、Kalesh Karunakaran、Lakshman Matta、Sok Hui Choo、Shailijia Panduga、Ronald N. Buckle、Randall N. Davis、Samuel A. Sakwa、Priya Gupta、Bruce J. Sargent、Nicholas A. Moore、Michele M. Luche、Grant J. Carr、Yuri L. Khmelnitsky、Jiffry Ismail、Mark Chung、Mei Bai、Wei Yee Leong、Nidhi Sachdev、Srividya Swaminathan、Andrew J. Mhyre

  DOI：10.1021/acs.jmedchem.6b00914

  日期：2016.9.22

  We previously disclosed the discovery of rationally designed N-((1-(4-(propylsulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide inhibitors of glycine transporter-1 (GlyT-1), represented by analogues 10 and 11. We describe herein further structure-activity relationship exploration of this series via an optimization strategy that primarily focused on the sulfonamide and benzamide appendages of the scaffold. These efforts led to the identification of advanced leads possessing a desirable balance of excellent in vitro GlyT-1 potency and selectivity, favorable ADME and in vitro pharmacological profiles, and suitable pharmacokinetic and safety characteristics. Representative analogue (+)-67 exhibited robust in vivo activity in the cerebral spinal fluid glycine biomarker model in both rodents and nonhuman primates. Furthermore, rodent microdialysis experiments also demonstrated that oral administration of (+)-67 significantly elevated extracellular glycine levels within the medial prefrontal cortex (mPFC).
• [EN] LIGANDS OF MELANOCORTIN RECEPTORS AND COMPOSITIONS AND METHODS RELATED THERETO<br/>[FR] LIGANDS DES RECEPTEURS DE LA MELANOCORTINE, ET COMPOSITIONS ET METHODES ASSOCIEES
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2004058735A3

  公开（公告）日：2007-12-27
• Synthesis and characterization of trans-4-(4-chlorophenyl)pyrrolidine-3-carboxamides of piperazinecyclohexanes as ligands for the melanocortin-4 receptor
  作者：Caroline W. Chen、Joe A. Tran、Beth A. Fleck、Fabio C. Tucci、Wanlong Jiang、Chen Chen

  DOI：10.1016/j.bmcl.2007.10.032

  日期：2007.12

  A series of trans-N-alkyl-4-(4-chlorophenyl)pyrrolidine-3-carboxamides of piperazinecyclohexanemethylamines was synthesized and characterized for binding and function at the melanocortin-4 receptor (MC4R), and several potent benzylamine derivatives were identified. Compound 18v was found to bind MC4R with potent affinity (K-i = 0.5 nM) and high selectivity over the other melanocortin subtypes and behaved as a functional antagonist IC50 = 48 nM). (c) 2007 Elsevier Ltd. All rights reserved.