Synthesis and antinociceptive activity of orally active opioid peptides: improvement of oral bioavailability by esterification

…, M Araki, T Miyamae, T Okayama, M Hagiwara…

Index: Ogawa, Tadashi; Araki, Mamoru; Miyamae, Tetsuhisa; Okayama, Toru; Hagiwara, Masaki; Sakurada, Shinobu; Morikawa, Tadanori Chemical and Pharmaceutical Bulletin, 2003 , vol. 51, # 7 p. 759 - 771

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Citation Number: 13

Abstract

To improve the oral bioavailability of a dermorphin tetrapeptide analog, N α-1-iminoethyl-Tyr- D-MetO-Phe-MeβAla-OH (III), 1) which has a potent analgesic activity after oral administration, various derivatives were synthesized to increase lipophilicity by esterification of the C-terminal carboxyl group and/or acylation of the phenolic hydroxyl group on Tyr 1. Antinociceptive activity was evaluated after subcutaneous or oral administration using the ...