Synthesis of enkephalin analogs. Part V. N-monosubstituted derivatives.
Synthesis of four new derivatives of enkephalin analogs: H-BuTyr-DMet-Gly- Phe-epsilon Ahx-OH 9, H-BzlTyr-DMet-Gly-Phe-epsilon Ahx-OH 12, H-Butyr-DMet-Gly- -Phe-epsilon Ahx-epsilon Ahx-OH 15 and H-BzlTyr-DMet-Gly-Phe-epsilon Ahx-OH is reported. They were examined for agonistic, antagonistic and analgesic activity. Compound 12 is the most potent among investigated peptides. Its agonistic activity in vitro is 7.85 x 10(-8) M/l (GPI) and 9.5 x 10(-7) M/l (MVD). None of the peptides showed antagonistic activity. Only compound 12 showed weak, not dose-dependent analgesic activity in rats.
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; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004745:Enkephalins / Q000138:chemical synthesis* / Q000737:chemistry; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism
D000596:Amino Acids; D004745:Enkephalins; D011957:Receptors, Opioid; D009270:Naloxone; D009020:Morphine