Synthesis and analgesic activities of endomorphin-2 and its analogues.
Endomorphin-2 (1; H-Tyr-Pro-Phe-Phe-NH2; EM2) and its novel cyclic asparagine (cycloAsn) analogues, H-Tyr-cAsn(CHPh)-Phe-Phe-NH2 (2) and H-Tyr-cAsn(CHMe2)-Phe-Phe-NH2 (3), were synthesized via liquid-phase synthesis. The structures of the products and intermediates were characterized by IR, 1H-NMR, MS, and HR-MS analyses. The antinociceptive activity of EM2 and its cyclic asparagine analogues were assessed in AcOH-induced abdominal constriction tests in mice with i.p. injection. The results show that the antinociceptive activities of EM2 and its cyclic asparagine analogue 2 were higher than those of aspirine and meperidine. Analogue 2 was observed to be a stronger analgesic with dose-dependence than EM2. The test mice did not show any tendency to be addicted while administrated of analogue 2 repeatedly and regularly.
Shi
Zhi-Hao
ZH
Institute of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, PR China.
Wei
Yun-Yang
YY
Wang
Chuan-Jin
CJ
Yu
Li
L
D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D001216:Asparagine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D011957:Receptors, Opioid / Q000819:agonists / Q000502:physiology
D000701:Analgesics, Opioid; D009842:Oligopeptides; D011957:Receptors, Opioid; C105294:endomorphin 2; D001216:Asparagine