title: α-Methylated simplified resiniferatoxin (sRTX) thiourea analogues as potent and stereospecific TRPV1 antagonists.
abstract: A series of α-methylated analogues of the potent sRTX thiourea antagonists were investigated as rTRPV1 ligands in order to examine the effect of α-methylation on receptor activity. The SAR analysis indicated that activity was stereospecific with the (R)-configuration of the newly formed chiral center providing high binding affinity and potent antagonism while the configuration of the C-region was not significant.
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Ho Shin
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Mi-Kyoung
authors.initials: MK
authors.lastname: Jin
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Sang-Uk
authors.initials: SU
authors.lastname: Kang
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Ju-Ok
authors.initials: JO
authors.lastname: Lim
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Phuong-Thao
authors.initials: PT
authors.lastname: Tran
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Van-Hai
authors.initials: VH
authors.lastname: Hoang
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Jihyae
authors.initials: J
authors.lastname: Ann
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Ha
authors.affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Larry V
authors.initials: LV
authors.lastname: Pearce
authors.affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Pavlyukovets
authors.affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Blumberg
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: jeewoo@snu.ac.kr.
authors.forename: Jeewoo
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008745:Methylation; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D013890:Thiourea / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004224:Diterpenes; D050916:TRPV Cation Channels; C024353:resiniferatoxin; D013890:Thiourea
keywords: Capsaicin; Resiniferatoxin; TRPV1 antagonist; Vanilloid receptor 1