4-Piperidines and 3-pyrrolidines as dual serotonin and noradrenaline reuptake inhibitors: Design, synthesis and structure-activity relationships

被引：16
|
作者：
Fish, Paul V. [1 ]
Andrews, Mark D. [1 ]
Fray, M. Jonathan [1 ]
Stobie, Alan [1 ]
Wakenhut, Florian [1 ]
Whitlock, Gavin A. [1 ]
机构：
[1] Pfizer Global Res & Dev, Sandwich Labs, Discovery Chem, Sandwich CT13 9NJ, Kent, England
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 10期
关键词：
Dual SNRI; Selective SRI; Selective NRI; Triple SNDRI; 4-Piperidine; 3-Piperidine; 3-Pyrrolidine; Monoamine reuptake inhibitor; DERIVATIVES; NOREPINEPHRINE; DRUGS;
D O I：
10.1016/j.bmcl.2009.03.090
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Single enantiomer [(aryloxy)(pyridinyl) methyl] piperidine and pyrrolidine derivatives 5-9 are inhibitors of monoamine reuptake. Structure-activity relationships established that monoamine reuptake inhibition are functions of amine, pyridine isomer, aryloxy ring substitution and stereochemistry. Consequently, selective NRIs, selective SRIs, dual SNRIs and triple SNDRIs were all identified. Dual SNRIs 51-a and 9c were evaluated in additional pharmacology and pharmacokinetic studies as representative examples from this series. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2829 / 2834
页数：6
相关论文
共 50 条
  • [1] A novel class of 3-(phenoxy-phenyl-methyl)-pyrrolidines as potent and balanced norepinephrine and serotonin reuptake inhibitors: Synthesis and structure-activity relationships
    Van Orden, Lori Jean
    Van Dyke, Priscilla M.
    Saito, D. Roland
    Church, Timothy J.
    Chang, Ray
    Smith, Jacqueline A. M.
    Martin, William J.
    Jaw-Tsai, Sarah
    Stangeland, Eric L.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (05) : 1456 - 1461
  • [2] Discovery and structure-activity relationships of novel selective norepinephrine and dual serotonin/norepinephrine reuptake inhibitors
    Boot, J
    Cases, M
    Clark, BP
    Findlay, J
    Gallagher, PT
    Hayhurst, L
    Man, T
    Montalbetti, C
    Rathmell, RE
    Rudyk, H
    Walter, MW
    Whatton, M
    Wood, V
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (03) : 699 - 703
  • [3] Design and synthesis of 4-benzylpiperidine carboxamides as dual serotonin and norepinephrine reuptake inhibitors
    Paudel, Suresh
    Cao, Yongkai
    Guo, Shuohan
    An, Byeongkwan
    Kim, Kyeong-Man
    Cheon, Seung Hoon
    BIOORGANIC & MEDICINAL CHEMISTRY, 2015, 23 (19) : 6418 - 6426
  • [4] Design and Synthesis of Arylamidine Derivatives as Serotonin/Norepinephrine Dual Reuptake Inhibitors
    Wen, Hui
    Qin, Wen
    Yang, Guangzhong
    Guo, Yanshen
    MOLECULES, 2019, 24 (03)
  • [5] Synthesis and structure-activity relationships of selective norepinephrine reuptake inhibitors (sNRI) with a heterocyclic ring constraint
    Hudson, Sarah
    Kiankarimi, Mehrak
    Eccles, Wendy
    Mostofi, Yalda S.
    Genicot, Marc J.
    Dwight, Wesley
    Fleck, Beth A.
    Gogas, Kathleen
    Wade, Warren S.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (16) : 4495 - 4498
  • [6] Triple reuptake inhibitors: Design, synthesis and structure-activity relationship of benzylpiperidine-tetrazoles
    Paudel, Suresh
    Min, Xiao
    Acharya, Srijan
    Khadka, Daulat Bikram
    Yoon, Goo
    Kim, Kyeong-Man
    Cheon, Seung Hoon
    BIOORGANIC & MEDICINAL CHEMISTRY, 2017, 25 (20) : 5278 - 5289
  • [7] A new phenolic series of indenopyridinone as topoisomerase inhibitors: Design, synthesis, and structure-activity relationships
    Shrestha, Aarajana
    Park, Seojeong
    Jang, Hae Jin
    Katila, Pramila
    Shrestha, Ritina
    Kwon, Youngjoo
    Lee, Eung-Seok
    BIOORGANIC & MEDICINAL CHEMISTRY, 2018, 26 (18) : 5212 - 5223
  • [8] Structure-activity relationships of norepinephrine reuptake inhibitors with benzothiadiazine dioxide or dihydrosulfostyril cores
    Fensome, Andrew
    Goldberg, Joel
    McComas, Casey C.
    Trybulski, Eugene J.
    Woodworth, Richard P.
    Deecher, Darlene C.
    Whiteside, Garth T.
    Zhang, Puwen
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (05) : 1555 - 1558
  • [9] Design, Synthesis, and Structure-Activity relationships of Evodiamine-Based topoisomerase (Top)/Histone deacetylase (HDAC) dual inhibitors
    Zhu, Fugui
    Meng, Xiangguo
    Liang, Huixin
    Sheng, Chunquan
    Dong, Guoqiang
    Liu, Dan
    Wu, Shanchao
    BIOORGANIC CHEMISTRY, 2022, 122
  • [10] Study on the design, synthesis and structure-activity relationships of new thiosemicarbazone compounds as tyrosinase inhibitors
    Song, Senchuan
    You, Ao
    Chen, Zhiyong
    Zhu, Guoxun
    Wen, Huan
    Song, Huacan
    Yi, Wei
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2017, 139 : 815 - 825
12345