Analysis of structure–activity relationships for the ‘A-region’ of N-(4-t-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as TRPV1 antagonists

Lee, Jeeyeon; Kang, Sang-Uk; Kil, Min-Jung; Shin, Moon Sam; Lim, Ju-Ok; Choi, Ho Jin; Jin, Michelle; Kim, Su Yeon; Kim, Sung-Eun; Lee, Yong‐Sil; Min, Kyung Hoon; Kim, Young‐Ho; Ha, Hee-Jin; Tran, Richard; Welter, Jacqueline D.; Wang, Yun; Szabó, Tamás; Pearce, Larry V.; Lundberg, Daniel J.; Tóth, Attila; Pavlyukovets, Vladimir A.; Morgan, Matthew A.; Blumberg, Peter M.

doi:10.1016/j.bmcl.2005.06.009

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Cited by 14 publications

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“…16 Recent SAR studies indicated that the modification of the A region, especially the modification of the 4-hydroxyl group, led to a complete loss of agonistic activity, 18 and replacing the B region linkage with a reverse amide, hydroxamate or thiourea altered the potency. 19 …”

Section: Introductionmentioning

confidence: 99%

The SAR analysis of TRPV1 agonists with the α-methylated B-region

Cho

Kim

et al. 2012

Bioorganic & Medicinal Chemistry Letters

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A series of TRPV1 agonists with amide, reverse amide, and thiourea groups in the B-region and their corresponding α-methylated analogues were investigated. Whereas the α–methylation of the amide B-region enhanced the binding affinities and potencies as agonists, that of the reverse amide and thiourea led to a reduction in receptor affinity. The analysis indicated that proper hydrogen bonding as well as steric effects in the B-region are critical for receptor binding.

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Section: Introductionmentioning

confidence: 99%

The SAR analysis of TRPV1 agonists with the α-methylated B-region

Cho

Kim

et al. 2012

Bioorganic & Medicinal Chemistry Letters

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“…The majority of the compounds have been identified through high-throughput screening experiments [13–15,17]. Some of these compounds were further optimized by isosteric replacements of structural fragments [18–20] and by structure–activity relationship (SAR) studies [9–11,21–30]. Very recently, also a cryo-EM structure of human TRPV1 in a resolution of 3.4 Å has been published.…”

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confidence: 99%