4073-43-2Relevant academic research and scientific papers
N-[4-(Methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: Analysis of structure-activity relationships for the 'C-Region'
Lee, Jeewoo,Kang, Sang-Uk,Lim, Ju-Ok,Choi, Hyun-Kyung,Jin, Mi-Kyung,Toth, Attila,Pearce, Larry V.,Tran, Richard,Wang, Yun,Szabo, Tamas,Blumberg, Peter M.
, p. 371 - 385 (2007/10/03)
We recently reported that N-(4-t-butylbenzyl)-N′-[4- (methylsulfonylamino)benzyl] thiourea (2) was a high affinity antagonist of the vanilloid receptor with a binding affinity of Ki=63 nM and an antagonism of Ki=53.9 nM in rat VR1 heterologously expressed in Chinese hamster ovary (CHO) cells (Mol. Pharmacol. 2002, 62, 947-956). In an effort to further improve binding affinity and antagonistic potency, we have modified the C-region of the lead 4-t-butylbenzyl group with diverse surrogates, such as araalkyl, alkyl, 4-alkynylbenzyl, indanyl, 3,3-diarylpropyl, 4-alkoxybenzyl, 4-substituted piperazine and piperidine. The lipophilic surrogates, arylalkyl and alkyl, conferred modest decreases in binding affinities and antagonistic potencies; the groups having heteroatoms resulted in dramatic decreases. Our findings indicate that 4-t-butylbenzyl is one of the most favorable groups for high receptor binding and potent antagonism to VR1 in this structural series.
