2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists

Jihyae Ann; Yooran Ki; Suyoung Yoon; Myeong Seop Kim; Jung Un Lee; Changhoon Kim; Sunho Lee; Aeran Jung; Jisoo Baek; Sunhye Hong; Sun Choi; Larry V. Pearce; Timothy E. Esch; Noe A. Turcios; Nancy E. Lewin; Adebowale E. Ogunjirin; Brienna K.A. Herold; Anna K. McCall; Peter M. Blumberg; Jeewoo Lee

doi:10.1016/j.bmc.2016.01.051

2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists

Jihyae Ann, Yooran Ki, Suyoung Yoon, Myeong Seop Kim, Jung Un Lee, Changhoon Kim, Sunho Lee, Aeran Jung, Jisoo Baek, Sunhye Hong, Sun Choi, Larry V. Pearce, Timothy E. Esch, Noe A. Turcios, Nancy E. Lewin, Adebowale E. Ogunjirin, Brienna K.A. Herold, Anna K. McCall, Peter M. Blumberg, Jeewoo Lee

Department of Pharmaceutical Sciences

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

10 Scopus citations

Abstract

A series of 2-sulfonamidopyridine C-region derivatives of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamide were investigated as hTRPV1 ligands. Systematic modification on the 2-sulfonamido group provided highly potent TRPV1 antagonists. The N-benzyl phenylsulfonamide derivatives 12 and 23 in particular showed higher affinities than that of lead compound 1. Compound 12 exhibited strong analgesic activity in the formalin pain model. Docking analysis of its chiral S-form 12S in our hTRPV1 homology model indicated that its high affinity might arise from additional hydrophobic interactions not present in lead compound 1S.

Original language	English
Pages (from-to)	1231-1240
Number of pages	10
Journal	Bioorganic and Medicinal Chemistry
Volume	24
Issue number	6
DOIs	https://doi.org/10.1016/j.bmc.2016.01.051
State	Published - 15 Mar 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd. All rights reserved.

Keywords

Analgesic
TRPV1 antagonists
Vanilloid receptor 1

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Ann, J., Ki, Y., Yoon, S., Kim, M. S., Lee, J. U., Kim, C., Lee, S., Jung, A., Baek, J., Hong, S., Choi, S., Pearce, L. V., Esch, T. E., Turcios, N. A., Lewin, N. E., Ogunjirin, A. E., Herold, B. K. A., McCall, A. K., Blumberg, P. M., & Lee, J. (2016). 2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists. Bioorganic and Medicinal Chemistry, 24(6), 1231-1240. https://doi.org/10.1016/j.bmc.2016.01.051

@article{8792565ae16142ed89f1657b0fdda397,

title = "2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists",

abstract = "A series of 2-sulfonamidopyridine C-region derivatives of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamide were investigated as hTRPV1 ligands. Systematic modification on the 2-sulfonamido group provided highly potent TRPV1 antagonists. The N-benzyl phenylsulfonamide derivatives 12 and 23 in particular showed higher affinities than that of lead compound 1. Compound 12 exhibited strong analgesic activity in the formalin pain model. Docking analysis of its chiral S-form 12S in our hTRPV1 homology model indicated that its high affinity might arise from additional hydrophobic interactions not present in lead compound 1S.",

keywords = "Analgesic, TRPV1 antagonists, Vanilloid receptor 1",

author = "Jihyae Ann and Yooran Ki and Suyoung Yoon and Kim, {Myeong Seop} and Lee, {Jung Un} and Changhoon Kim and Sunho Lee and Aeran Jung and Jisoo Baek and Sunhye Hong and Sun Choi and Pearce, {Larry V.} and Esch, {Timothy E.} and Turcios, {Noe A.} and Lewin, {Nancy E.} and Ogunjirin, {Adebowale E.} and Herold, {Brienna K.A.} and McCall, {Anna K.} and Blumberg, {Peter M.} and Jeewoo Lee",

year = "2016",

month = mar,

day = "15",

doi = "10.1016/j.bmc.2016.01.051",

language = "English",

volume = "24",

pages = "1231--1240",

journal = "Bioorganic and Medicinal Chemistry",

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Ann, J, Ki, Y, Yoon, S, Kim, MS, Lee, JU, Kim, C, Lee, S, Jung, A, Baek, J, Hong, S, Choi, S, Pearce, LV, Esch, TE, Turcios, NA, Lewin, NE, Ogunjirin, AE, Herold, BKA, McCall, AK, Blumberg, PM & Lee, J 2016, '2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists', Bioorganic and Medicinal Chemistry, vol. 24, no. 6, pp. 1231-1240. https://doi.org/10.1016/j.bmc.2016.01.051

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T1 - 2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists

AU - Ann, Jihyae

AU - Ki, Yooran

AU - Yoon, Suyoung

AU - Kim, Myeong Seop

AU - Lee, Jung Un

AU - Kim, Changhoon

AU - Lee, Sunho

AU - Jung, Aeran

AU - Baek, Jisoo

AU - Hong, Sunhye

AU - Choi, Sun

AU - Pearce, Larry V.

AU - Esch, Timothy E.

AU - Turcios, Noe A.

AU - Lewin, Nancy E.

AU - Ogunjirin, Adebowale E.

AU - Herold, Brienna K.A.

AU - McCall, Anna K.

AU - Blumberg, Peter M.

AU - Lee, Jeewoo

PY - 2016/3/15

Y1 - 2016/3/15

N2 - A series of 2-sulfonamidopyridine C-region derivatives of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamide were investigated as hTRPV1 ligands. Systematic modification on the 2-sulfonamido group provided highly potent TRPV1 antagonists. The N-benzyl phenylsulfonamide derivatives 12 and 23 in particular showed higher affinities than that of lead compound 1. Compound 12 exhibited strong analgesic activity in the formalin pain model. Docking analysis of its chiral S-form 12S in our hTRPV1 homology model indicated that its high affinity might arise from additional hydrophobic interactions not present in lead compound 1S.

AB - A series of 2-sulfonamidopyridine C-region derivatives of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamide were investigated as hTRPV1 ligands. Systematic modification on the 2-sulfonamido group provided highly potent TRPV1 antagonists. The N-benzyl phenylsulfonamide derivatives 12 and 23 in particular showed higher affinities than that of lead compound 1. Compound 12 exhibited strong analgesic activity in the formalin pain model. Docking analysis of its chiral S-form 12S in our hTRPV1 homology model indicated that its high affinity might arise from additional hydrophobic interactions not present in lead compound 1S.

KW - Analgesic

KW - TRPV1 antagonists

KW - Vanilloid receptor 1

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SN - 0968-0896

VL - 24

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EP - 1240

JO - Bioorganic and Medicinal Chemistry

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IS - 6

ER -

2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists

Abstract

Bibliographical note

Keywords

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