Design and synthesis of KNT-127, a δ-opioid receptor agonist effective by systemic administration.
We have reported previously the novel δ-opioid agonist, SN-28, which was more potent in in vitro assays than the prototype δ-agonists, TAN-67 and SNC-80. However, when administered by subcutaneous injection, this compound showed no analgesic effect at dosages greater than 30mg/kg in the acetic acid writhing test. We speculated that SN-28 was not effective in the test because the presence of the charged ammonium groups prevented its penetration through the blood-brain barrier. On the basis of our proposal, we designed the novel δ-agonist, KNT-127, which was effective with systemic administration.
Nagase
Hiroshi
H
School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan. nagaseh@pharm.kitasato-u.ac.jp
Nemoto
Toru
T
Matsubara
Ayaka
A
Saito
Manabu
M
Yamamoto
Naoshi
N
Osa
Yumiko
Y
Hirayama
Shigeto
S
Nakajima
Mayumi
M
Nakao
Kaoru
K
Mochizuki
Hidenori
H
Fujii
Hideaki
H
D019342:Acetic Acid; D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects; D007202:Indicators and Reagents; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D051379:Mice; D009019:Morphinans / Q000138:chemical synthesis* / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists*; D013329:Structure-Activity Relationship
D000701:Analgesics, Opioid; D001549:Benzamides; D007202:Indicators and Reagents; C555233:KNT 127; D009019:Morphinans; D010879:Piperazines; D011804:Quinolines; D017465:Receptors, Opioid, delta; C094142:TAN 67; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D019342:Acetic Acid