Analysis of structure-activity relationships for the 'B-region' of N-(3-acyloxy-2-benzylpropyl)-N(')-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: discovery of an N-hydroxythiourea analogue with potent analgesic activity.
The structural modifications on the B-region of the potent and high affinity vanilloid receptor (VR1) lead ligand N-(3-acyloxy-2-benzylpropyl)-N(')-[4-(methylsulfonylamino)benzyl]thiourea were investigated by the replacement of the thiourea with diverse isosteric functional groups. Structure-activity analysis indicated that the A-region in this series was the primary factor in determining the agonistic/antagonistic activities regardless of the B-region. The N(C)-hydroxy thiourea analogues (12, 13) showed excellent analgesic activities in the acetic acid writhing assay compared to the parent thiourea analogues.
Lee
Jeewoo
J
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim-Dong, Kwanak-Ku, Seoul 151-742, South Korea. jeewoo@snu.ac.kr
Kang
Sang-Uk
SU
Choi
Hyun-Kyung
HK
Lee
Jiyoun
J
Lim
Ju-Ok
JO
Kil
Min-Jung
MJ
Jin
Mi-Kyung
MK
Kim
Kang-Pil
KP
Sung
Jong-Hyuk
JH
Chung
Suk-Jae
SJ
Ha
Hee-Jin
HJ
Kim
Young-Ho
YH
Pearce
Larry V
LV
Tran
Richard
R
Lundberg
Daniel J
DJ
Wang
Yun
Y
Toth
Attila
A
Blumberg
Peter M
PM
D000700:Analgesics / Q000737:chemistry* / Q000494:pharmacology*; D011955:Receptors, Drug / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000737:chemistry* / Q000494:pharmacology*
D000700:Analgesics; D011955:Receptors, Drug; D013890:Thiourea