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

Rahul S. Bhondwe; Dong Wook Kang; Myeong Seop Kim; Ho Shin Kim; Seul Gi Park; Karam Son; Sun Choi; Krystle A. Lang Kuhs; Vladimir A. Pavlyukovets; Larry V. Pearce; Peter M. Blumberg; Jeewoo Lee

doi:10.1016/j.bmcl.2012.04.034

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

Rahul S. Bhondwe, Dong Wook Kang, Myeong Seop Kim, Ho Shin Kim, Seul Gi Park, Karam Son, Sun Choi, Krystle A. Lang Kuhs, Vladimir A. Pavlyukovets, Larry V. Pearce, Peter M. Blumberg, Jeewoo Lee

Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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.

Original language	English
Pages (from-to)	3656-3660
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	11
DOIs	https://doi.org/10.1016/j.bmcl.2012.04.034
State	Published - 1 Jun 2012

Bibliographical note

Funding Information:
This research was supported by Grants from the National Research Foundation of Korea (NRF) ( R11-2007-107-02001-0 ), Grants from the NLRL program (2011-0028885), Brain Research Center of the 21st Century Frontier Research Program (2011-K000289) funded by MEST and NRF, the Ewha Global Top 5 Grant 2011 of Ewha Womans University, and was supported in part by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute (Project Z1A BC 005270).

Keywords

Capsaicin
Molecular modeling
Resiniferatoxin
TRPV1 antagonist
Vanilloid receptor 1

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10.1016/j.bmcl.2012.04.034

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Bhondwe, R. S., Kang, D. W., Kim, M. S., Kim, H. S., Park, S. G., Son, K., Choi, S., Lang Kuhs, K. A., Pavlyukovets, V. A., Pearce, L. V., Blumberg, P. M., & Lee, J. (2012). Structure-activity relationships and molecular modeling of the N-(3-pivaloyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl] thiourea template for TRPV1 antagonism. Bioorganic and Medicinal Chemistry Letters, 22(11), 3656-3660. https://doi.org/10.1016/j.bmcl.2012.04.034

@article{5f937790e5b344ff83ab78d5c92a2036,

title = "Structure-activity relationships and molecular modeling of the N-(3-pivaloyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl] thiourea template for TRPV1 antagonism",

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.",

keywords = "Capsaicin, Molecular modeling, Resiniferatoxin, TRPV1 antagonist, Vanilloid receptor 1",

author = "Bhondwe, {Rahul S.} and Kang, {Dong Wook} and Kim, {Myeong Seop} and Kim, {Ho Shin} and Park, {Seul Gi} and Karam Son and Sun Choi and {Lang Kuhs}, {Krystle A.} and Pavlyukovets, {Vladimir A.} and Pearce, {Larry V.} and Blumberg, {Peter M.} and Jeewoo Lee",

note = "Funding Information: This research was supported by Grants from the National Research Foundation of Korea (NRF) ( R11-2007-107-02001-0 ), Grants from the NLRL program (2011-0028885), Brain Research Center of the 21st Century Frontier Research Program (2011-K000289) funded by MEST and NRF, the Ewha Global Top 5 Grant 2011 of Ewha Womans University, and was supported in part by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute (Project Z1A BC 005270). ",

year = "2012",

month = jun,

day = "1",

doi = "10.1016/j.bmcl.2012.04.034",

language = "English",

volume = "22",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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Bhondwe, RS, Kang, DW, Kim, MS, Kim, HS, Park, SG, Son, K, Choi, S, Lang Kuhs, KA, Pavlyukovets, VA, Pearce, LV, Blumberg, PM & Lee, J 2012, 'Structure-activity relationships and molecular modeling of the N-(3-pivaloyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl] thiourea template for TRPV1 antagonism', Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 11, pp. 3656-3660. https://doi.org/10.1016/j.bmcl.2012.04.034

Structure-activity relationships and molecular modeling of the N-(3-pivaloyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl] thiourea template for TRPV1 antagonism. / Bhondwe, Rahul S.; Kang, Dong Wook; Kim, Myeong Seop et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 22, No. 11, 01.06.2012, p. 3656-3660.

Research output: Contribution to journal › Article › peer-review

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T1 - Structure-activity relationships and molecular modeling of the N-(3-pivaloyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl] thiourea template for TRPV1 antagonism

AU - Bhondwe, Rahul S.

AU - Kang, Dong Wook

AU - Kim, Myeong Seop

AU - Kim, Ho Shin

AU - Park, Seul Gi

AU - Son, Karam

AU - Choi, Sun

AU - Lang Kuhs, Krystle A.

AU - Pavlyukovets, Vladimir A.

AU - Pearce, Larry V.

AU - Blumberg, Peter M.

AU - Lee, Jeewoo

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N2 - 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.

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KW - Capsaicin

KW - Molecular modeling

KW - Resiniferatoxin

KW - TRPV1 antagonist

KW - Vanilloid receptor 1

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M3 - Article

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AN - SCOPUS:84861186828

SN - 0960-894X

VL - 22

SP - 3656

EP - 3660

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 11

ER -

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

Abstract

Bibliographical note

Keywords

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