title: Phenolic modification as an approach to improve the pharmacology of the 3-acyloxy-2-benzylpropyl homovanillic amides and thioureas, a promising class of vanilloid receptor agonists and analgesics.
abstract: In order to improve the analgesic activity and pharmacokinetics of thioureas 2 and 3, which we previously developed as potent vanilloid receptor (VR) agonists, we prepared and characterized phenolic modifications of them and of their amide surrogates (7, 8). The aminoethyl analogue of the amide template 13 was a potent analgesic with an EC50=0.96 microg/kg in the AA-induced writhing test and with better in vivo stability than the parent phenol.
authors.affiliation: Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Shinlim-Dong, Kwanak-Ku, 151-742, Seoul, South Korea. jeewoo@snu.ac.kr
authors.forename: Jeewoo
authors.initials: J
authors.lastname: Lee
authors.forename: Jiyoun
authors.initials: J
authors.lastname: Lee
authors.forename: Myung-Sim
authors.initials: MS
authors.lastname: Kang
authors.forename: Kang-Pil
authors.initials: KP
authors.lastname: Kim
authors.forename: Suk-Jae
authors.initials: SJ
authors.lastname: Chung
authors.forename: Peter M
authors.initials: PM
authors.lastname: Blumberg
authors.forename: Jung-Bum
authors.initials: JB
authors.lastname: Yi
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Park
mesh_terms: D000577:Amides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000700:Analgesics / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006719:Homovanillic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D008297:Male; D009474:Neurons / Q000187:drug effects; D019800:Phenol / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000819:agonists*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000577:Amides; D000700:Analgesics; D011955:Receptors, Drug; D019800:Phenol; D013890:Thiourea; D002118:Calcium; D006719:Homovanillic Acid