Literature DB >> 25937016

α-Substituted 2-(3-fluoro-4-methylsulfonamidophenyl)acetamides as potent TRPV1 antagonists.

Phuong-Thao Tran1, Ho Shin Kim1, Jihyae Ann1, Sung-Eun Kim1, Changhoon Kim1, Mannkyu Hong1, Van-Hai Hoang1, Van T H Ngo1, Sunhye Hong2, Minghua Cui2, Sun Choi2, Peter M Blumberg3, Robert Frank-Foltyn4, Gregor Bahrenberg4, Hannelore Stockhausen4, Thomas Christoph4, Jeewoo Lee5.   

Abstract

A series of α-substituted acetamide derivatives of previously reported 2-(3-fluoro-4-methylsulfonamidophenyl)propanamide leads (1, 2) were investigated for antagonism of hTRPV1 activation by capsaicin. Compound 34, which possesses an α-m-tolyl substituent, showed highly potent and selective antagonism of capsaicin with Ki(CAP)=0.1 nM. It thus reflected a 3-fold improvement in potency over parent 1. Docking analysis using our homology model indicated that the high potency of 34 might be attributed to a specific hydrophobic interaction of the m-tolyl group with the receptor.
Copyright © 2015 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Analgesic; Capsaicin; Molecular modeling; TRPV1 antagonist

Mesh：

Substances：

Year:  2015        PMID： 25937016      PMCID： PMC6957262          DOI： 10.1016/j.bmcl.2015.04.024

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  26 in total

Review 1.  Vanilloid (Capsaicin) receptors and mechanisms.

Authors:  A Szallasi; P M Blumberg
Journal:  Pharmacol Rev       Date:  1999-06       Impact factor: 25.468

2.  Analgesic potential of TRPV1 antagonists.

Authors:  Philip R Kym; Michael E Kort; Charles W Hutchins
Journal:  Biochem Pharmacol       Date:  2009-03-05       Impact factor: 5.858

Review 3.  Therapeutic potential of vanilloid receptor TRPV1 agonists and antagonists as analgesics: Recent advances and setbacks.

Authors:  Gilbert Y Wong; Narender R Gavva
Journal:  Brain Res Rev       Date:  2008-12-25

Review 4.  Modulation of the TRPV1 channel: current clinical trials and recent patents with focus on neurological conditions.

Authors:  Luciano De Petrocellis; Aniello S Moriello
Journal:  Recent Pat CNS Drug Discov       Date:  2013-12

5.  The cloned capsaicin receptor integrates multiple pain-producing stimuli.

Authors:  M Tominaga; M J Caterina; A B Malmberg; T A Rosen; H Gilbert; K Skinner; B E Raumann; A I Basbaum; D Julius
Journal:  Neuron       Date:  1998-09       Impact factor: 17.173

6.  Structural insights into transient receptor potential vanilloid type 1 (TRPV1) from homology modeling, flexible docking, and mutational studies.

Authors:  Jin Hee Lee; Yoonji Lee; HyungChul Ryu; Dong Wook Kang; Jeewoo Lee; Jozsef Lazar; Larry V Pearce; Vladimir A Pavlyukovets; Peter M Blumberg; Sun Choi
Journal:  J Comput Aided Mol Des       Date:  2011-03-30       Impact factor: 3.686

Review 7.  Transient receptor potential vanilloid-1 antagonists: a survey of recent patent literature.

Authors:  Eric A Voight; Michael E Kort
Journal:  Expert Opin Ther Pat       Date:  2010-09       Impact factor: 6.674

8.  2-(3-Fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists: structure activity relationships of the 2-oxy pyridine C-region.

Authors:  Shivaji A Thorat; Dong Wook Kang; HyungChul Ryu; Myeong Seop Kim; Ho Shin Kim; Jihyae Ann; Taehwan Ha; Sung-Eun Kim; Karam Son; Sun Choi; Peter M Blumberg; Robert Frank; Gregor Bahrenberg; Klaus Schiene; Thomas Christoph; Jeewoo Lee
Journal:  Eur J Med Chem       Date:  2013-04-11       Impact factor: 6.514

Review 9.  Clinical development of TRPV1 antagonists: targeting a pivotal point in the pain pathway.

Authors:  Martin J Gunthorpe; Boris A Chizh
Journal:  Drug Discov Today       Date:  2008-12-26       Impact factor: 7.851

10.  Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia.

Authors:  Andras Garami; Yury P Shimansky; Eszter Pakai; Daniela L Oliveira; Narender R Gavva; Andrej A Romanovsky
Journal:  J Neurosci       Date:  2010-01-27       Impact factor: 6.167
View more
  4 in total

1.  t-Butyl pyridine and phenyl C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.

Authors:  Sunho Lee; Dong Wook Kang; HyungChul Ryu; Changhoon Kim; Jihyae Ann; Hobin Lee; Eunhye Kim; Sunhye Hong; Sun Choi; Peter M Blumberg; Robert Frank-Foltyn; Gregor Bahrenberg; Hannelore Stockhausen; Thomas Christoph; Jeewoo Lee
Journal:  Bioorg Med Chem       Date:  2017-03-06       Impact factor: 3.641

2.  Pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.

Authors:  Sunho Lee; Changhoon Kim; Jihyae Ann; Shivaji A Thorat; Eunhye Kim; Jongmi Park; Sun Choi; Peter M Blumberg; Robert Frank-Foltyn; Gregor Bahrenberg; Hannelore Stockhausen; Thomas Christoph; Jeewoo Lee
Journal:  Bioorg Med Chem Lett       Date:  2017-08-12       Impact factor: 2.823

3.  Discovery of N-(3-fluoro-4-methylsulfonamidomethylphenyl)urea as a potent TRPV1 antagonistic template.

Authors:  Jihyae Ann; Wei Sun; Xing Zhou; Aeran Jung; Jisoo Baek; Sunho Lee; Changhoon Kim; Suyoung Yoon; Sunhye Hong; Sun Choi; Noe A Turcios; Brienna K A Herold; Timothy E Esch; Nancy E Lewin; Adelle Abramovitz; Larry V Pearce; Peter M Blumberg; Jeewoo Lee
Journal:  Bioorg Med Chem Lett       Date:  2016-06-07       Impact factor: 2.823

4.  Prediction of Lipophilicity and Pharmacokinetics of Chloroacetamides by Chemometric Approach.

Authors:  Gyöngyi Vastag; Suzana Apostolov; Borko Matijević
Journal:  Iran J Pharm Res       Date:  2018       Impact factor: 1.696
  4 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.