title: Synthesis and evaluation of 3-aminopropionyl substituted fentanyl analogues for opioid activity.
abstract: An enkephalin analogue coupled to 'aminofentanyl' has been synthesized and tested for biological activities at the mu and delta opioid receptors. Aminofentanyl which represents a structural derivative of fentanyl has been synthesized by acylation of 1-(2-phenethyl)-4-(N-anilino)piperidine with phthaloyl protected beta-alaninyl chloride in the presence of DIPEA, followed by deprotection with hydrazine hydrate. Aminofentanyl has also been successfully acylated with ethyl isocyanate, various acid anhydrides, to further investigate structure-activity relationships of these new fentanyl derivatives. Among the new derivatives compound 7 which carries a Tyr-D-Ala-Gly-Phe opioid message sequence showed good opioid affinity (1 nM at both delta and mu opioid receptors) and bioactivity (34.9 nM in MVD and 42 nM in GPI/LMMP bioassays).
authors.affiliation: Department of Chemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Ravil R
authors.initials: RR
authors.lastname: Petrov
authors.forename: Ruben S
authors.initials: RS
authors.lastname: Vardanyan
authors.forename: Yeon S
authors.initials: YS
authors.lastname: Lee
authors.forename: Shou-wu
authors.initials: SW
authors.lastname: Ma
authors.forename: Peg
authors.initials: P
authors.lastname: Davis
authors.forename: Lucinda J
authors.initials: LJ
authors.lastname: Begay
authors.forename: Josephine Y
authors.initials: JY
authors.lastname: Lai
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D000818:Animals; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009294:Narcotics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010847:Picolines; D051381:Rats; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D009294:Narcotics; D010847:Picolines; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C015672:2-amino-4-picoline; D005283:Fentanyl