Synthesis of enkephalin analogs. Part VI. N,N-disubstituted derivatives.
Synthesis of four new N,N-disubstituted derivatives of enkephalin analogs: All2Tyr-DMet-Gly-Phe-epsilon Ahx-OMe 5, Bu2Tyr-DMet-Gly-Phe-epsilon Ahx-OMe 6, All2Tyr-DMet-Gly-Phe-epsilon Ahx-epsilon Ahx-OMe 11 and Bu2Tyr-DMet-Gly-Phe-epsilon Ahx-epsilon Ahx-OMe 12 is reported. they were tested for agonistic and antagonistic activity. Compound 5 is a little more potent agonist (IC50 = 1.9 x 10(-7) M/l, GPI) than compound 6(IC50 = 7.2 x 10(-7) M/l, GPI). They both are highly selective to mu receptor, because they show no trace of activity to delta receptor in concentration up to 10(-5) M/l. Compound 11 and 12 are less active and not selective as agonists. None of these compounds showed antagonistic activity.
Paruszewski
R
R
Department of Pharmaceutical Chemistry, Medical Academy, Warszawa, Poland.
Matusiak
R
R
Rostafińska-Suchar
G
G
Gumułka
S W
SW
Misterek
K
K
Dorociak
A
A
D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004745:Enkephalins / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009020:Morphine / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
D004745:Enkephalins; D009020:Morphine