The SAR analysis of TRPV1 agonists with the α-methylated B-region

被引：5
作者：
Cho, Yongsung [1 ]
Kim, Myeong Seop [1 ]
Kim, Ho Shin [1 ]
Ann, Jihyae [1 ]
Lee, Jiyoun [2 ]
Pearce, Larry V. [3 ]
Pavlyukovets, Vladimir A. [3 ]
Morgan, Matthew A. [3 ]
Blumberg, Peter M. [3 ]
Lee, Jeewoo [1 ]
机构：
[1] Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea
[2] Sungshin Womens Univ, Dept Global Med Sci, Seoul 142732, South Korea
[3] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 16期
基金：
美国国家卫生研究院;
关键词：
Vanilloid receptor 1; TRPV1; agonist; Capsaicin; VANILLOID RECEPTOR TRPV1; CAPSAICIN RECEPTOR; A-REGION; ANTAGONISTS; PAIN; CHANNEL; ANALGESICS; MECHANISMS; ANALOGS;
D O I：
10.1016/j.bmcl.2012.06.059
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of TRPV1 agonists with amide, reverse amide, and thiourea groups in the B-region and their corresponding alpha-methylated analogues were investigated. Whereas the alpha-methylation of the amide B-region enhanced the binding affinities and potencies as agonists, that of the reverse amide and thiourea led to a reduction in receptor affinity. The analysis indicated that proper hydrogen bonding as well as steric effects in the B-region are critical for receptor binding. (c) 2012 Elsevier Ltd. All rights reserved.
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收藏
页码：5227 / 5231
页数：5
相关论文
共 22 条
  • [1] The paradoxical role of the transient receptor potential vanilloid 1 receptor in inflammation
    Alawi, Khadija
    Keeble, Julie
    [J]. PHARMACOLOGY & THERAPEUTICS, 2010, 125 (02) : 181 - 195
  • [2] Euphorbium: Modern research on its active principle, resiniferatoxin, revives an ancient medicine
    Appendino, G
    Szallasi, A
    [J]. LIFE SCIENCES, 1997, 60 (10) : 681 - 696
  • [3] The capsaicin receptor: a heat-activated ion channel in the pain pathway
    Caterina, MJ
    Schumacher, MA
    Tominaga, M
    Rosen, TA
    Levine, JD
    Julius, D
    [J]. NATURE, 1997, 389 (6653) : 816 - 824
  • [4] TRPing the switch on pain: an introduction to the chemistry and biology of capsaicin and TRPV1
    Conway, Stuart J.
    [J]. CHEMICAL SOCIETY REVIEWS, 2008, 37 (08) : 1530 - 1545
  • [5] Clinical development of TRPV1 antagonists: targeting a pivotal point in the pain pathway
    Gunthorpe, Martin J.
    Chizh, Boris A.
    [J]. DRUG DISCOVERY TODAY, 2009, 14 (1-2) : 56 - 67
  • [6] Direct activation of capsaicin receptors by products of lipoxygenases: Endogenous capsaicin-like substances
    Hwang, SW
    Cho, H
    Kwak, J
    Lee, SY
    Kang, CJ
    Jung, J
    Cho, S
    Min, KH
    Suh, YG
    Kim, D
    Oh, U
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (11) : 6155 - 6160
  • [7] Molecular mechanisms of nociception
    Julius, D
    Basbaum, AI
    [J]. NATURE, 2001, 413 (6852) : 203 - 210
  • [8] Halogenation of 4-hydroxy/amino-3-methoxyphenyl acetamide TRPV1 agonists showed enhanced antagonism to capsaicin
    Kang, Dong Wook
    Kim, Yong Soo
    Lim, Kwang Su
    Kim, Myeong Seop
    Pearce, Larry V.
    Pavlyukovets, Vladimir A.
    Tao, Andy K.
    Lang-Kuhs, Krystle A.
    Blumberg, Peter M.
    Lee, Jeewoo
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2010, 18 (22) : 8092 - 8105
  • [9] N-4-t-Butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure-activity relationships in the A-region
    Kim, Yong Soo
    Kil, Min-Jung
    Kang, Sang-Uk
    Ryu, HyungChul
    Kim, Myeong Seop
    Cho, Yongsung
    Bhondwe, Rahul S.
    Thorat, Shivaji A.
    Sun, Wei
    Liu, Keliang
    Lee, Jin Hee
    Choi, Sun
    Pearce, Larry V.
    Pavlyukovets, Vladimir A.
    Morgan, Matthew A.
    Tran, Richard
    Lazar, Jozsef
    Blumberg, Peter M.
    Lee, Jeewoo
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (01) : 215 - 224
  • [10] Krause James E, 2005, Curr Opin Investig Drugs, V6, P48
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