α-Substituted N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists

Jae Uk Chung; Su Yeon Kim; Ju Ok Lim; Hyun Kyung Choi; Sang Uk Kang; Hae Seok Yoon; Hyung Chul Ryu; Dong Wook Kang; Jeewoo Lee; Bomi Kang; Sun Choi; Attila Toth; Larry V. Pearce; Vladimir A. Pavlyukovets; Daniel J. Lundberg; Peter M. Blumberg

doi:10.1016/j.bmc.2007.06.041

α-Substituted N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists

Jae Uk Chung, Su Yeon Kim, Ju Ok Lim, Hyun Kyung Choi, Sang Uk Kang, Hae Seok Yoon, Hyung Chul Ryu, Dong Wook Kang, Jeewoo Lee, Bomi Kang, Sun Choi, Attila Toth, Larry V. Pearce, Vladimir A. Pavlyukovets, Daniel J. Lundberg, Peter M. Blumberg

Department of Pharmaceutical Sciences

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

29 Scopus citations

Abstract

A series of α-substituted N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. α-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).

Original language	English
Pages (from-to)	6043-6053
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	15
Issue number	18
DOIs	https://doi.org/10.1016/j.bmc.2007.06.041
State	Published - 15 Sep 2007

Bibliographical note

Funding Information:
This work was supported by Grant R01-2004-000-10132-0 from the Basic Research Program of the Korea Science & Engineering Foundation and by Grant No. R15-2006-020 from the National Core Research Center (NCRC) program of the Ministry of Science & Technology (MOST) through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University. This work was also supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We thank Richard Tran and Matthew A. Morgan for technical assistance.

Keywords

Analgesic
TRPV1 antagonists

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10.1016/j.bmc.2007.06.041

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Chung, J. U., Kim, S. Y., Lim, J. O., Choi, H. K., Kang, S. U., Yoon, H. S., Ryu, H. C., Kang, D. W., Lee, J., Kang, B., Choi, S., Toth, A., Pearce, L. V., Pavlyukovets, V. A., Lundberg, D. J., & Blumberg, P. M. (2007). α-Substituted N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists. Bioorganic and Medicinal Chemistry, 15(18), 6043-6053. https://doi.org/10.1016/j.bmc.2007.06.041

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title = "α-Substituted N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists",

abstract = "A series of α-substituted N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. α-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, Ki = 41 and 39.2 nM and Ki(ant) = 4.5 and 37 nM).",

keywords = "Analgesic, TRPV1 antagonists",

author = "Chung, {Jae Uk} and Kim, {Su Yeon} and Lim, {Ju Ok} and Choi, {Hyun Kyung} and Kang, {Sang Uk} and Yoon, {Hae Seok} and Ryu, {Hyung Chul} and Kang, {Dong Wook} and Jeewoo Lee and Bomi Kang and Sun Choi and Attila Toth and Pearce, {Larry V.} and Pavlyukovets, {Vladimir A.} and Lundberg, {Daniel J.} and Blumberg, {Peter M.}",

note = "Funding Information: This work was supported by Grant R01-2004-000-10132-0 from the Basic Research Program of the Korea Science & Engineering Foundation and by Grant No. R15-2006-020 from the National Core Research Center (NCRC) program of the Ministry of Science & Technology (MOST) through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University. This work was also supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We thank Richard Tran and Matthew A. Morgan for technical assistance.",

year = "2007",

month = sep,

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doi = "10.1016/j.bmc.2007.06.041",

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Chung, JU, Kim, SY, Lim, JO, Choi, HK, Kang, SU, Yoon, HS, Ryu, HC, Kang, DW, Lee, J, Kang, B, Choi, S, Toth, A, Pearce, LV, Pavlyukovets, VA, Lundberg, DJ & Blumberg, PM 2007, 'α-Substituted N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists', Bioorganic and Medicinal Chemistry, vol. 15, no. 18, pp. 6043-6053. https://doi.org/10.1016/j.bmc.2007.06.041

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T1 - α-Substituted N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists

AU - Chung, Jae Uk

AU - Kim, Su Yeon

AU - Lim, Ju Ok

AU - Choi, Hyun Kyung

AU - Kang, Sang Uk

AU - Yoon, Hae Seok

AU - Ryu, Hyung Chul

AU - Kang, Dong Wook

AU - Lee, Jeewoo

AU - Kang, Bomi

AU - Choi, Sun

AU - Toth, Attila

AU - Pearce, Larry V.

AU - Pavlyukovets, Vladimir A.

AU - Lundberg, Daniel J.

AU - Blumberg, Peter M.

N1 - Funding Information: This work was supported by Grant R01-2004-000-10132-0 from the Basic Research Program of the Korea Science & Engineering Foundation and by Grant No. R15-2006-020 from the National Core Research Center (NCRC) program of the Ministry of Science & Technology (MOST) through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University. This work was also supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We thank Richard Tran and Matthew A. Morgan for technical assistance.

PY - 2007/9/15

Y1 - 2007/9/15

N2 - A series of α-substituted N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. α-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, Ki = 41 and 39.2 nM and Ki(ant) = 4.5 and 37 nM).

AB - A series of α-substituted N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. α-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, Ki = 41 and 39.2 nM and Ki(ant) = 4.5 and 37 nM).

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ER -

α-Substituted N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists

Abstract

Bibliographical note

Keywords

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