Design and synthesis of μ-selective opioidomimetic peptides

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This project started as International Scientific Research by The Ministry of Education, Culture, Sports, Science and Technology in 1999 and then as Grant-in-Aid for Scientific Research (C) in 2000 and 2001. Therefore, Dr. Lawrence H. Lazarus and Ms. Sharon D. Bryant of National Institute of Environmental Health Sciences, USA were investigators in this project. Dr. Yoshio Okada has been engaged in synthesis of peptides based on the peptide synthesis we made a plan of this project with objective to develop novel type of anti-pain medicine, and obtained following results. 1) We could develop synthetic methodologies ofpeptides. 2) We designed and synthesized endomorphin derivatives and obtained compounds which exhibited potent μ-opioid receptor agonistic activity and δ-opioid receptor antagonistic activity. We designated them as bifunctional opioid mimetics. 3) Employing new method to synthesize pyrazinones from dipeptidyl chloromethyl ketones, novel type opioid memetics containing pyrazinone ring were prepared. 4) Instead of pyrazinone ring, NH_2(CH_2)nNH_2 (n=2-8)were employed to prepare novel types of anti-pain drugs. 5) Compounds obtained above exhibited more potent in vitro and in vivo activity than morphine.6) International conference Annual ' Conference on Opioid Mimetic Analgesics 2002" was successfully held from 17 to 19 of March, 2002 at Awaji Yumebutai International Conference Center and we exchanged our mutual interest concerning the developme t of anti-pain medicines."