1003002-74-1Relevant academic research and scientific papers
Discovery of 2-(3,5-difluoro-4-methylsulfonaminophenyl)propanamides as potent TRPV1 antagonists
Kim, Changhoon,Ann, Jihyae,Lee, Sunho,Sun, Wei,Blumberg, Peter M.,Frank-Foltyn, Robert,Bahrenberg, Gregor,Stockhausen, Hannelore,Christoph, Thomas,Lee, Jeewoo
, p. 2539 - 2542 (2018/06/07)
A series of A-region analogues of 2-(3-fluoro-4-methylsufonamidophenyl) propanamide 1 were investigated as TRPV1 antagonists. The analysis of structure-activity relationship indicated that a fluoro group at the 3- (or/and) 5-position and a methylsulfonamido group at the 4-position were optimal for antagonism of TRPV1 activation by capsaicin. The most potent antagonist 6 not only exhibited potent antagonism of activation of hTRPV1 by capsaicin, low pH and elevated temperature but also displayed highly potent antagonism of activation of rTRPV1 by capsaicin. Further studies demonstrated that antagonist 6 blocked the hypothermic effect of capsaicin in vivo, consistent with its in vitro mechanism, and it showed promising analgesic activity in the formalin animal model.
N-4-t-Butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure-activity relationships in the A-region
Kim, Yong Soo,Kil, Min-Jung,Kang, Sang-Uk,Ryu, Hyungchul,Kim, Myeong Seop,Cho, Yongsung,Bhondwe, Rahul S.,Thorat, Shivaji A.,Sun, Wei,Liu, Keliang,Lee, Jin Hee,Choi, Sun,Pearce, Larry V.,Pavlyukovets, Vladimir A.,Morgan, Matthew A.,Tran, Richard,Lazar, Jozsef,Blumberg, Peter M.,Lee, Jeewoo
, p. 215 - 224 (2012/02/16)
Structure-activity relationships for the A-region in a series of N-4-t-butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamides as TRPV1 antagonists have been investigated. Among them, the 3-fluoro analogue 54 showed high binding affinity and potent antagonism for both rTRPV1 and hTRPV1 in CHO cells. Its stereospecific activity was demonstrated with marked selectivity for the (S)-configuration (54S versus 54R). A docking study of 54S with our hTRPV1 homology model highlighted crucial hydrogen bonds between the ligand and the receptor contributing to its potency.
Stereospecific high-affinity TRPV1 antagonists: Chiral N-(2-benzyl-3- pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues
Ryu, Hyungchul,Jin, Mi-Kyoung,Su, Yeon Kim,Choi, Hyun-Kyung,Kang, Sang-Uk,Dong, Wook Kang,Lee, Jeewoo,Pearce, Larry V.,Pavlyukovets, Vladimir A.,Morgan, Matthew A.,Tran, Richard,Toth, Attila,Lundberg, Daniel J.,Blumberg, Peter M.
, p. 57 - 67 (2008/09/18)
Previously, we reported the thiourea antagonists 2a and 2b as potent and high affinity TRPV1 antagonists. For further optimization of the lead compounds, a series of their amide and α-substituted amide surrogates were investigated and novel chiral N-(2-be
