当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > t-Butyl pyridine and phenyl C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.

t-Butyl pyridine and phenyl C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.

Abstract：

:A series of 2-substituted 6-t-butylpyridine and 4-t-butylphenyl C-region analogues of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides were investigated for hTRPV1 antagonism. The analysis of structure activity relationships indicated that the pyridine derivatives generally exhibited a little better antagonism than did the corresponding phenyl surrogates for most of the series. Among the compounds, compound 7 showed excellent antagonism toward capsaicin activation with Ki=0.1nM and compound 60S demonstrated a strong antiallodynic effect with 83% MPE at 10mg/kg in the neuropathic pain model. The docking study of 7S in our hTRPV1 homology model indicated that the interactions between the A/B-regions of 7S with Tyr511 and the interactions between the t-butyl and ethyl groups in the C-region of 7S with the two hydrophobic binding pockets of hTRPV1 contributed to the high potency.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Lee S,Kang DW,Ryu H,Kim C,Ann J,Lee H,Kim E,Hong S,Choi S,Blumberg PM,Frank-Foltyn R,Bahrenberg G,Stockhausen H,Christoph T,Lee J

doi

10.1016/j.bmc.2017.03.004

subject

Has Abstract

pub_date

2017-04-15 00:00:00

pages

2451-2462

issue

8

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(17)30311-5

journal_volume

25

pub_type

杂志文章

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