title: 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.
abstract: 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.
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim-Dong, Kwanak-Ku, Seoul 151-742, South Korea. jeewoo@snu.ac.kr
authors.forename: Jeewoo
authors.initials: J
authors.lastname: Lee
authors.forename: Sang-Uk
authors.initials: SU
authors.lastname: Kang
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Choi
authors.forename: Jiyoun
authors.initials: J
authors.lastname: Lee
authors.forename: Ju-Ok
authors.initials: JO
authors.lastname: Lim
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kil
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Jin
authors.forename: Kang-Pil
authors.initials: KP
authors.lastname: Kim
authors.forename: Jong-Hyuk
authors.initials: JH
authors.lastname: Sung
authors.forename: Suk-Jae
authors.initials: SJ
authors.lastname: Chung
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Ha
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Larry V
authors.initials: LV
authors.lastname: Pearce
authors.forename: Richard
authors.initials: R
authors.lastname: Tran
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lundberg
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Attila
authors.initials: A
authors.lastname: Toth
authors.forename: Peter M
authors.initials: PM
authors.lastname: Blumberg
mesh_terms: D000700:Analgesics / Q000737:chemistry* / Q000494:pharmacology*; D011955:Receptors, Drug / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D011955:Receptors, Drug; D013890:Thiourea