title: Design and synthesis of KNT-127, a δ-opioid receptor agonist effective by systemic administration.
abstract: 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.
authors.affiliation: School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan. nagaseh@pharm.kitasato-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
authors.forename: Toru
authors.initials: T
authors.lastname: Nemoto
authors.forename: Ayaka
authors.initials: A
authors.lastname: Matsubara
authors.forename: Manabu
authors.initials: M
authors.lastname: Saito
authors.forename: Naoshi
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Osa
authors.forename: Shigeto
authors.initials: S
authors.lastname: Hirayama
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nakajima
authors.forename: Kaoru
authors.initials: K
authors.lastname: Nakao
authors.forename: Hidenori
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujii
mesh_terms: 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
chemical_list: 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