Rational drug design and synthesis of a selective opioid receptor antagonist on the basis of the accessory site concept

Hideaki Fujii; Minoru Narita; Hirokazu Mizoguchi; Junichi Hirokawa; Koji Kawai; Toshiaki Tanaka; Leon F Tseng; Hiroshi Nagase

doi:10.1016/j.bmcl.2004.06.004

Rational drug design and synthesis of a selective opioid receptor antagonist on the basis of the accessory site concept

Bioorg Med Chem Lett. 2004 Aug 16;14(16):4241-3. doi: 10.1016/j.bmcl.2004.06.004.

Authors

Hideaki Fujii¹, Minoru Narita, Hirokazu Mizoguchi, Junichi Hirokawa, Koji Kawai, Toshiaki Tanaka, Leon F Tseng, Hiroshi Nagase

Affiliation

¹ Pharmaceutical Research Laboratories, Toray Industries, Inc., 1111, Tebiro, Kamakura Kanagawa 248-8555, Japan. hideaki_fujii@nts.toray.co.jp

PMID: 15261278
DOI: 10.1016/j.bmcl.2004.06.004

Abstract

To newly synthesize a selective opioid receptor antagonist, 17-(cyclopropylmethyl)-4,5 alpha-epoxy-6 beta,21-epoxymethano-3-hydroxy-6,14-endoethenomorphinan-7 alpha-(N-phenethyl)carboxamide was first designed from an opioid receptor agonist TAN-821 on the basis of the accessory site concept. The designed compound antagonized the agonistic effects induced by an opioid receptor agonist beta-endorphin on the rat vas deference test. Moreover, the designed compound blocked the antinociception induced by beta-endorphin given intracerebroventricularly.

MeSH terms

Animals
Drug Design*
Male
Morphinans / chemical synthesis*
Morphinans / chemistry
Morphinans / pharmacology
Narcotic Antagonists*
Rats
Receptors, Opioid
Vas Deferens / drug effects
beta-Endorphin / pharmacology

Substances

17-(cyclopropylmethyl)-4,5 alpha-epoxy-6 beta,21-epoxymethano-3-hydroxy-6,14-endoethenomorphinan-7 alpha-(N-phenethyl)carboxamide
Morphinans
Narcotic Antagonists
Receptors, Opioid
epsilon receptor
beta-Endorphin