Heterocycle-linked phenylbenzyl amides as novel TRPV1 antagonists and their TRPV1 binding modes: Constraint-induced enhancement of in vitro and in vivo activities

Nam Jung Kim; Fu Nan Li; Jin Hee Lee; Seul Gi Park; Kyeojin Kim; Changjin Lim; Young Taek Han; Hwayoung Yun; Jong Wha Jung; Hyeung Geun Park; Hee Doo Kim; Byoung Young Woo; Song Seok Shin; Sun Young Kim; Jin Kyu Choi; Yeon Su Jeong; Yanghui Park; Young Ho Park; Dae Duk Kim; Sun Choi; Young Ger Suh

doi:10.1002/asia.201200730

Heterocycle-linked phenylbenzyl amides as novel TRPV1 antagonists and their TRPV1 binding modes: Constraint-induced enhancement of in vitro and in vivo activities

Nam Jung Kim, Fu Nan Li, Jin Hee Lee, Seul Gi Park, Kyeojin Kim, Changjin Lim, Young Taek Han, Hwayoung Yun, Jong Wha Jung, Hyeung Geun Park, Hee Doo Kim, Byoung Young Woo, Song Seok Shin, Sun Young Kim, Jin Kyu Choi, Yeon Su Jeong, Yanghui Park, Young Ho Park, Dae Duk Kim, Sun ChoiYoung Ger Suh

Department of Pharmaceutical Sciences

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

6 Scopus citations

Abstract

A series of heterocycle-linked constrained phenylbenzyl amides were found to be TRPV1 antagonists with promising in vivo profiles. In particular, one of the analogues containing a furan linker exhibited excellent TRPV1 antagonistic activity and in vivo analgesic efficacy. In addition, the binding modes of dibenzyl thiourea, benzylphenethyl amide, and furan-linked phenylbenzyl amide were examined by using the flexible docking study within the rTRPV1 homology model. Flexibility not desired: A series of heterocycle-linked constrained phenylbenzyl amides were found to be TRPV1 antagonists with promising in vivo profiles. In particular, one of the analogues containing a furan linker exhibited excellent TRPV1 antagonistic activity and in vivo analgesic efficacy. In addition, the binding modes of dibenzyl thiourea, benzylphenethyl amide, and furan-linked phenylbenzyl amide were examined by using the flexible docking study within the rTRPV1 homology model.

Original language	English
Pages (from-to)	400-409
Number of pages	10
Journal	Chemistry - An Asian Journal
Volume	8
Issue number	2
DOIs	https://doi.org/10.1002/asia.201200730
State	Published - Feb 2013

Keywords

TRVP1
antagonists
ligand design
medicinal chemistry
molecular modeling

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Kim, N. J., Li, F. N., Lee, J. H., Park, S. G., Kim, K., Lim, C., Han, Y. T., Yun, H., Jung, J. W., Park, H. G., Kim, H. D., Woo, B. Y., Shin, S. S., Kim, S. Y., Choi, J. K., Jeong, Y. S., Park, Y., Park, Y. H., Kim, D. D., ... Suh, Y. G. (2013). Heterocycle-linked phenylbenzyl amides as novel TRPV1 antagonists and their TRPV1 binding modes: Constraint-induced enhancement of in vitro and in vivo activities. Chemistry - An Asian Journal, 8(2), 400-409. https://doi.org/10.1002/asia.201200730

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title = "Heterocycle-linked phenylbenzyl amides as novel TRPV1 antagonists and their TRPV1 binding modes: Constraint-induced enhancement of in vitro and in vivo activities",

abstract = "A series of heterocycle-linked constrained phenylbenzyl amides were found to be TRPV1 antagonists with promising in vivo profiles. In particular, one of the analogues containing a furan linker exhibited excellent TRPV1 antagonistic activity and in vivo analgesic efficacy. In addition, the binding modes of dibenzyl thiourea, benzylphenethyl amide, and furan-linked phenylbenzyl amide were examined by using the flexible docking study within the rTRPV1 homology model. Flexibility not desired: A series of heterocycle-linked constrained phenylbenzyl amides were found to be TRPV1 antagonists with promising in vivo profiles. In particular, one of the analogues containing a furan linker exhibited excellent TRPV1 antagonistic activity and in vivo analgesic efficacy. In addition, the binding modes of dibenzyl thiourea, benzylphenethyl amide, and furan-linked phenylbenzyl amide were examined by using the flexible docking study within the rTRPV1 homology model.",

keywords = "TRVP1, antagonists, ligand design, medicinal chemistry, molecular modeling",

author = "Kim, {Nam Jung} and Li, {Fu Nan} and Lee, {Jin Hee} and Park, {Seul Gi} and Kyeojin Kim and Changjin Lim and Han, {Young Taek} and Hwayoung Yun and Jung, {Jong Wha} and Park, {Hyeung Geun} and Kim, {Hee Doo} and Woo, {Byoung Young} and Shin, {Song Seok} and Kim, {Sun Young} and Choi, {Jin Kyu} and Jeong, {Yeon Su} and Yanghui Park and Park, {Young Ho} and Kim, {Dae Duk} and Sun Choi and Suh, {Young Ger}",

year = "2013",

month = feb,

doi = "10.1002/asia.201200730",

language = "English",

volume = "8",

pages = "400--409",

journal = "Chemistry - An Asian Journal",

issn = "1861-4728",

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Kim, NJ, Li, FN, Lee, JH, Park, SG, Kim, K, Lim, C, Han, YT, Yun, H, Jung, JW, Park, HG, Kim, HD, Woo, BY, Shin, SS, Kim, SY, Choi, JK, Jeong, YS, Park, Y, Park, YH, Kim, DD, Choi, S & Suh, YG 2013, 'Heterocycle-linked phenylbenzyl amides as novel TRPV1 antagonists and their TRPV1 binding modes: Constraint-induced enhancement of in vitro and in vivo activities', Chemistry - An Asian Journal, vol. 8, no. 2, pp. 400-409. https://doi.org/10.1002/asia.201200730

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AU - Kim, Nam Jung

AU - Li, Fu Nan

AU - Lee, Jin Hee

AU - Park, Seul Gi

AU - Kim, Kyeojin

AU - Lim, Changjin

AU - Han, Young Taek

AU - Yun, Hwayoung

AU - Jung, Jong Wha

AU - Park, Hyeung Geun

AU - Kim, Hee Doo

AU - Woo, Byoung Young

AU - Shin, Song Seok

AU - Kim, Sun Young

AU - Choi, Jin Kyu

AU - Jeong, Yeon Su

AU - Park, Yanghui

AU - Park, Young Ho

AU - Kim, Dae Duk

AU - Choi, Sun

AU - Suh, Young Ger

PY - 2013/2

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N2 - A series of heterocycle-linked constrained phenylbenzyl amides were found to be TRPV1 antagonists with promising in vivo profiles. In particular, one of the analogues containing a furan linker exhibited excellent TRPV1 antagonistic activity and in vivo analgesic efficacy. In addition, the binding modes of dibenzyl thiourea, benzylphenethyl amide, and furan-linked phenylbenzyl amide were examined by using the flexible docking study within the rTRPV1 homology model. Flexibility not desired: A series of heterocycle-linked constrained phenylbenzyl amides were found to be TRPV1 antagonists with promising in vivo profiles. In particular, one of the analogues containing a furan linker exhibited excellent TRPV1 antagonistic activity and in vivo analgesic efficacy. In addition, the binding modes of dibenzyl thiourea, benzylphenethyl amide, and furan-linked phenylbenzyl amide were examined by using the flexible docking study within the rTRPV1 homology model.

AB - A series of heterocycle-linked constrained phenylbenzyl amides were found to be TRPV1 antagonists with promising in vivo profiles. In particular, one of the analogues containing a furan linker exhibited excellent TRPV1 antagonistic activity and in vivo analgesic efficacy. In addition, the binding modes of dibenzyl thiourea, benzylphenethyl amide, and furan-linked phenylbenzyl amide were examined by using the flexible docking study within the rTRPV1 homology model. Flexibility not desired: A series of heterocycle-linked constrained phenylbenzyl amides were found to be TRPV1 antagonists with promising in vivo profiles. In particular, one of the analogues containing a furan linker exhibited excellent TRPV1 antagonistic activity and in vivo analgesic efficacy. In addition, the binding modes of dibenzyl thiourea, benzylphenethyl amide, and furan-linked phenylbenzyl amide were examined by using the flexible docking study within the rTRPV1 homology model.

KW - TRVP1

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KW - ligand design

KW - medicinal chemistry

KW - molecular modeling

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DO - 10.1002/asia.201200730

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SN - 1861-4728

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SP - 400

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JO - Chemistry - An Asian Journal

JF - Chemistry - An Asian Journal

IS - 2

ER -

Heterocycle-linked phenylbenzyl amides as novel TRPV1 antagonists and their TRPV1 binding modes: Constraint-induced enhancement of in vitro and in vivo activities

Abstract

Keywords

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