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.
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.
Lee
Jeewoo
J
Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Shinlim-Dong, Kwanak-Ku, 151-742, Seoul, South Korea. jeewoo@snu.ac.kr
Lee
Jiyoun
J
Kang
Myung-Sim
MS
Kim
Kang-Pil
KP
Chung
Suk-Jae
SJ
Blumberg
Peter M
PM
Yi
Jung-Bum
JB
Park
Young Ho
YH
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
D000577:Amides; D000700:Analgesics; D011955:Receptors, Drug; D019800:Phenol; D013890:Thiourea; D002118:Calcium; D006719:Homovanillic Acid