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Your search keyword '"Pavlyukovets VA"' showing total 6 results
Start Over Author "Pavlyukovets VA" Topic thiourea
6 results on '"Pavlyukovets VA"'

1. α-Methylated simplified resiniferatoxin (sRTX) thiourea analogues as potent and stereospecific TRPV1 antagonists.

Author

Kim HS, Jin MK, Kang SU, Lim JO, Tran PT, Hoang VH, Ann J, Ha TH, Pearce LV, Pavlyukovets VA, Blumberg PM, and Lee J

Subjects
Animals, CHO Cells, Cricetinae, Cricetulus, Diterpenes chemistry, Humans, Methylation, Molecular Structure, Protein Binding drug effects, Rats, Stereoisomerism, Structure-Activity Relationship, Thiourea analogs & derivatives, Thiourea chemistry, Diterpenes chemical synthesis, Diterpenes pharmacology, TRPV Cation Channels antagonists & inhibitors, Thiourea chemical synthesis, Thiourea pharmacology
Abstract

A series of α-methylated analogues of the potent sRTX thiourea antagonists were investigated as rTRPV1 ligands in order to examine the effect of α-methylation on receptor activity. The SAR analysis indicated that activity was stereospecific with the (R)-configuration of the newly formed chiral center providing high binding affinity and potent antagonism while the configuration of the C-region was not significant., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Published
2014
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2. Structure-activity relationships and molecular modeling of the N-(3-pivaloyloxy-2-benzylpropyl)-N'-[4-(methylsulfonylamino)benzyl] thiourea template for TRPV1 antagonism.

Author

Bhondwe RS, Kang DW, Kim MS, Kim HS, Park SG, Son K, Choi S, Kuhs KA, Pavlyukovets VA, Pearce LV, Blumberg PM, and Lee J

Subjects
Animals, Binding Sites, CHO Cells, Cricetinae, Cricetulus, Protein Structure, Tertiary, Rats, Structure-Activity Relationship, TRPV Cation Channels agonists, TRPV Cation Channels metabolism, Thiourea chemical synthesis, Molecular Dynamics Simulation, TRPV Cation Channels antagonists & inhibitors, Thiourea chemistry
Abstract

The structure-activity relationships of N-(3-acyloxy-2-benzylpropyl)-N'-4-[(methylsulfonylamino)benzyl] thioureas, which represent simplified RTX-based vanilloids, were investigated by varying the distances between the four principal pharmacophores and assessing binding and antagonistic activity on rTRPV1. The analysis indicated that a 3-pivaloyloxy-2-benzylpropyl C-region conferred the best potency in binding affinity and antagonism. The molecular modeling of this best template with the tetrameric homology model of rTRPV1 was performed to identify its binding interactions with the receptor., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Published
2012
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3. Alpha-substituted N-(4-tert-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists.

Author

Chung JU, Kim SY, Lim JO, Choi HK, Kang SU, Yoon HS, Ryu H, Kang DW, Lee J, Kang B, Choi S, Toth A, Pearce LV, Pavlyukovets VA, Lundberg DJ, and Blumberg PM

Subjects
Animals, CHO Cells, Calcium metabolism, Capsaicin pharmacology, Cells, Cultured, Cricetinae, Cricetulus, Models, Molecular, Molecular Structure, Rats, Stereoisomerism, Structure-Activity Relationship, Thiourea chemical synthesis, Thiourea chemistry, TRPV Cation Channels antagonists & inhibitors, Thiourea pharmacology
Abstract

A series of alpha-substituted N-(4-tert-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. alpha-Methyl substituted analogues showed potent and stereospecific antagonism to the action of capsaicin on rat TRPV1 heterologously expressed in Chinese hamster ovary cells. In particular, compounds 14 and 18, which possess the R-configuration, exhibited excellent potencies (respectively, K(i)=41 and 39.2 nM and K(i(ant))=4.5 and 37 nM).

Published
2007
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4. Halogenation of 4-hydroxy-3-methoxybenzyl thiourea TRPV1 agonists showed enhanced antagonism to capsaicin.

Author

Kang DW, Ryu H, Lee J, Lang KA, Pavlyukovets VA, Pearce LV, Ikeda T, Lazar J, and Blumberg PM

Subjects
Animals, Bromine chemistry, CHO Cells, Cricetinae, Cricetulus, Halogens chemistry, Iodine chemistry, Structure-Activity Relationship, Thiourea chemical synthesis, Thiourea chemistry, Thiourea pharmacology, Capsaicin antagonists & inhibitors, TRPV Cation Channels agonists, Thiourea analogs & derivatives
Abstract

Selected potent TRPV1 agonists (1-6) have been modified by 5- or 6-halogenation on the aromatic A-region to analyze their effects on potency and efficacy (agonism versus antagonism). The halogenation caused enhanced functional antagonism at TRPV1 compared to the corresponding prototype agonists. The analysis of SAR indicated that the antagonism was enhanced as the size of the halogen increased (I>Br>Cl) and when the 6-position was halogenated. Compounds 23c and 31b were found to be potent full antagonists with K(i) (as functional antagonist)=23.1 and 30.3 nM in rTRPV1/CHO system, respectively.

Published
2007
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5. Analysis of structure-activity relationships for the 'B-region' of N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]-thiourea analogues as TRPV1 antagonists.

Author

Lee J, Jin MK, Kang SU, Kim SY, Lee J, Shin M, Hwang J, Cho S, Choi YS, Choi HK, Kim SE, Suh YG, Lee YS, Kim YH, Ha HJ, Toth A, Pearce LV, Tran R, Szabo T, Welter JD, Lundberg DJ, Wang Y, Lazar J, Pavlyukovets VA, Morgan MA, and Blumberg PM

Subjects
Animals, CHO Cells, Cricetinae, Ligands, Models, Molecular, Protein Structure, Tertiary, Structure-Activity Relationship, Sulfonamides chemistry, TRPV Cation Channels chemistry, TRPV Cation Channels metabolism, Thiocarbamates chemical synthesis, Thiocarbamates chemistry, Thiourea chemistry, Sulfonamides pharmacology, TRPV Cation Channels antagonists & inhibitors, Thiourea analogs & derivatives, Thiourea pharmacology
Abstract

The structure-activity relationships for the 'B-region' of N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. A docking model of potent antagonist 2 with the sensor region of TRPV1 is proposed.

Published
2005
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6. Analysis of structure-activity relationships for the 'A-region' of N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues as TRPV1 antagonists.

Author

Lee J, Kang SU, Kil MJ, Shin M, Lim JO, Choi HK, Jin MK, Kim SY, Kim SE, Lee YS, Min KH, Kim YH, Ha HJ, Tran R, Welter JD, Wang Y, Szabo T, Pearce LV, Lundberg DJ, Toth A, Pavlyukovets VA, Morgan MA, and Blumberg PM

Subjects
Animals, CHO Cells, Calcium metabolism, Cricetinae, Ligands, Molecular Structure, Rats, Structure-Activity Relationship, Sulfonamides chemistry, TRPV Cation Channels metabolism, Thiourea chemistry, Sulfonamides pharmacology, TRPV Cation Channels antagonists & inhibitors, Thiourea analogs & derivatives, Thiourea pharmacology
Abstract

The structure-activity relationships for the 'A-region' of N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. The 2-halogen analogues showed enhanced antagonism compared to the prototype antagonist.

Published
2005
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