Analysis of structure-activity relationships for the 'B-region' of N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: Discovery of an N-hydroxythiourea analogue with potent analgesic activity

Jeewoo Lee; Sang Uk Kang; Hyun Kyung Choi; Jiyoun Lee; Ju Ok Lim; Min Jung Kil; Mi Kyung Jin; Kang Pil Kim; Jong Hyuk Sung; Suk Jae Chung; Hee Jin Ha; Young Ho Kim; Larry V. Pearce; Richard Tran; Daniel J. Lundberg; Yun Wang; Attila Toth; Peter M. Blumberg

doi:10.1016/j.bmcl.2004.02.002

Analysis of structure-activity relationships for the 'B-region' of N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: Discovery of an N-hydroxythiourea analogue with potent analgesic activity

Jeewoo Lee, Sang Uk Kang, Hyun Kyung Choi, Jiyoun Lee, Ju Ok Lim, Min Jung Kil, Mi Kyung Jin, Kang Pil Kim, Jong Hyuk Sung, Suk Jae Chung, Hee Jin Ha, Young Ho Kim, Larry V. Pearce, Richard Tran, Daniel J. Lundberg, Yun Wang, Attila Toth, Peter M. Blumberg

Department of Pharmacy

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

13 Citations (Scopus)

Abstract

The structural modifications on the B-region of the potent and high affinity vanilloid receptor (VR1) lead ligand N-(3-acyloxy-2-benzylpropyl)- N^′-[4-(methylsulfonylamino)benzyl]thiourea were investigated by the replacement of the thiourea with diverse isosteric functional groups. Structure-activity analysis indicated that the A-region in this series was the primary factor in determining the agonistic/antagonistic activities regardless of the B-region. The N_C-hydroxy thiourea analogues (12, 13) showed excellent analgesic activities in the acetic acid writhing assay compared to the parent thiourea analogues.

Original language	English
Pages (from-to)	2291-2297
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	14
Issue number	9
DOIs	https://doi.org/10.1016/j.bmcl.2004.02.002
Publication status	Published - 2004 May 3

Bibliographical note

Funding Information:
This work was supported by a grant (02-PJ1-PG11-VN01-SV01-0009) from the Ministry of Health & Welfare, R.O.K.

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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Lee, J., Kang, S. U., Choi, H. K., Lee, J., Lim, J. O., Kil, M. J., Jin, M. K., Kim, K. P., Sung, J. H., Chung, S. J., Ha, H. J., Kim, Y. H., Pearce, L. V., Tran, R., Lundberg, D. J., Wang, Y., Toth, A., & Blumberg, P. M. (2004). Analysis of structure-activity relationships for the 'B-region' of N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: Discovery of an N-hydroxythiourea analogue with potent analgesic activity. Bioorganic and Medicinal Chemistry Letters, 14(9), 2291-2297. https://doi.org/10.1016/j.bmcl.2004.02.002

Lee, Jeewoo ; Kang, Sang Uk ; Choi, Hyun Kyung et al. / Analysis of structure-activity relationships for the 'B-region' of N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists : Discovery of an N-hydroxythiourea analogue with potent analgesic activity. In: Bioorganic and Medicinal Chemistry Letters. 2004 ; Vol. 14, No. 9. pp. 2291-2297.

@article{26aed314d98b4ac6b30966ddbc17cf55,

title = "Analysis of structure-activity relationships for the 'B-region' of N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: Discovery of an N-hydroxythiourea analogue with potent analgesic activity",

abstract = "The structural modifications on the B-region of the potent and high affinity vanilloid receptor (VR1) lead ligand N-(3-acyloxy-2-benzylpropyl)- N′-[4-(methylsulfonylamino)benzyl]thiourea were investigated by the replacement of the thiourea with diverse isosteric functional groups. Structure-activity analysis indicated that the A-region in this series was the primary factor in determining the agonistic/antagonistic activities regardless of the B-region. The NC-hydroxy thiourea analogues (12, 13) showed excellent analgesic activities in the acetic acid writhing assay compared to the parent thiourea analogues.",

author = "Jeewoo Lee and Kang, {Sang Uk} and Choi, {Hyun Kyung} and Jiyoun Lee and Lim, {Ju Ok} and Kil, {Min Jung} and Jin, {Mi Kyung} and Kim, {Kang Pil} and Sung, {Jong Hyuk} and Chung, {Suk Jae} and Ha, {Hee Jin} and Kim, {Young Ho} and Pearce, {Larry V.} and Richard Tran and Lundberg, {Daniel J.} and Yun Wang and Attila Toth and Blumberg, {Peter M.}",

note = "Funding Information: This work was supported by a grant (02-PJ1-PG11-VN01-SV01-0009) from the Ministry of Health & Welfare, R.O.K.",

year = "2004",

month = may,

day = "3",

doi = "10.1016/j.bmcl.2004.02.002",

language = "English",

volume = "14",

pages = "2291--2297",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

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Lee, J, Kang, SU, Choi, HK, Lee, J, Lim, JO, Kil, MJ, Jin, MK, Kim, KP, Sung, JH, Chung, SJ, Ha, HJ, Kim, YH, Pearce, LV, Tran, R, Lundberg, DJ, Wang, Y, Toth, A & Blumberg, PM 2004, 'Analysis of structure-activity relationships for the 'B-region' of N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: Discovery of an N-hydroxythiourea analogue with potent analgesic activity', Bioorganic and Medicinal Chemistry Letters, vol. 14, no. 9, pp. 2291-2297. https://doi.org/10.1016/j.bmcl.2004.02.002

Analysis of structure-activity relationships for the 'B-region' of N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists : Discovery of an N-hydroxythiourea analogue with potent analgesic activity. / Lee, Jeewoo; Kang, Sang Uk; Choi, Hyun Kyung et al.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 14, No. 9, 03.05.2004, p. 2291-2297.

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

TY - JOUR

T1 - Analysis of structure-activity relationships for the 'B-region' of N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists

T2 - Discovery of an N-hydroxythiourea analogue with potent analgesic activity

AU - Lee, Jeewoo

AU - Kang, Sang Uk

AU - Choi, Hyun Kyung

AU - Lee, Jiyoun

AU - Lim, Ju Ok

AU - Kil, Min Jung

AU - Jin, Mi Kyung

AU - Kim, Kang Pil

AU - Sung, Jong Hyuk

AU - Chung, Suk Jae

AU - Ha, Hee Jin

AU - Kim, Young Ho

AU - Pearce, Larry V.

AU - Tran, Richard

AU - Lundberg, Daniel J.

AU - Wang, Yun

AU - Toth, Attila

AU - Blumberg, Peter M.

N1 - Funding Information: This work was supported by a grant (02-PJ1-PG11-VN01-SV01-0009) from the Ministry of Health & Welfare, R.O.K.

PY - 2004/5/3

Y1 - 2004/5/3

N2 - The structural modifications on the B-region of the potent and high affinity vanilloid receptor (VR1) lead ligand N-(3-acyloxy-2-benzylpropyl)- N′-[4-(methylsulfonylamino)benzyl]thiourea were investigated by the replacement of the thiourea with diverse isosteric functional groups. Structure-activity analysis indicated that the A-region in this series was the primary factor in determining the agonistic/antagonistic activities regardless of the B-region. The NC-hydroxy thiourea analogues (12, 13) showed excellent analgesic activities in the acetic acid writhing assay compared to the parent thiourea analogues.

AB - The structural modifications on the B-region of the potent and high affinity vanilloid receptor (VR1) lead ligand N-(3-acyloxy-2-benzylpropyl)- N′-[4-(methylsulfonylamino)benzyl]thiourea were investigated by the replacement of the thiourea with diverse isosteric functional groups. Structure-activity analysis indicated that the A-region in this series was the primary factor in determining the agonistic/antagonistic activities regardless of the B-region. The NC-hydroxy thiourea analogues (12, 13) showed excellent analgesic activities in the acetic acid writhing assay compared to the parent thiourea analogues.

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AN - SCOPUS:11144355751

SN - 0960-894X

VL - 14

SP - 2291

EP - 2297

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 9

ER -

Lee J, Kang SU, Choi HK, Lee J, Lim JO, Kil MJ et al. Analysis of structure-activity relationships for the 'B-region' of N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: Discovery of an N-hydroxythiourea analogue with potent analgesic activity. Bioorganic and Medicinal Chemistry Letters. 2004 May 3;14(9):2291-2297. doi: 10.1016/j.bmcl.2004.02.002

Analysis of structure-activity relationships for the 'B-region' of N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: Discovery of an N-hydroxythiourea analogue with potent analgesic activity

Abstract

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