2-(4-Methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure-activity relationships in the B and C-regions.
On the basis of the previous lead N-4-t-butylbenzyl 2-(3-fluoro-4-methylsulfonylaminophenyl) propanamide (3) as a potent TRPV1 antagonist, structure-activity relationships for the B (propanamide part) and C-region (4-t-butylbenzyl part) have been investigated for rTRPV1 in CHO cells. The B-region was modified with dimethyl, cyclopropyl and reverse amides and then the C-region was replaced with 4-substituted phenyl, aryl alkyl and diaryl alkyl derivatives. Among them, compound 50 showed high binding affinity with K(i)=21.5nM, which was twofold more potent than 3 and compound 54 exhibited potent antagonism with K(i(ant))=8.0nM comparable to 3.
Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
Wei
W
Sun
Keliang
K
Liu
HyungChul
H
Ryu
Dong Wook
DW
Kang
Yong Soo
YS
Kim
Myeong Seop
MS
Kim
Yongsung
Y
Cho
Rahul S
RS
Bhondwe
Shivaji A
SA
Thorat
Ho Shin
HS
Kim
Larry V
LV
Pearce
Vladimir A
VA
Pavlyukovets
Richard
R
Tran
Matthew A
MA
Morgan
Jozsef
J
Lazar
Christopher B
CB
Ryder
Attila
A
Toth
Peter M
PM
Blumberg
Jeewoo
J
Lee
D000700:Analgesics / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D008698:Mesylates / Q000737:chemistry* / Q000494:pharmacology*; D010666:Phenylpropionates / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
C572122:2-(4-methylsulfonylaminophenyl)propanamide; D000700:Analgesics; D008698:Mesylates; D010666:Phenylpropionates; D050916:TRPV Cation Channels