Synthesis of new opioid derivatives with a propellane skeleton and their pharmacology: part 1 |
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| Authors: | Yamamoto Naoshi Fujii Hideaki Nemoto Toru Nakajima Ryo Momen Shinobu Izumimoto Naoki Hasebe Ko Mochizuki Hidenori Nagase Hiroshi |
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| Institution: | a School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan
b Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1, Tebiro, Kamakura, Kanagawa 248-8555, Japan |
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| Abstract: | The observation that 17-cyclopropylmethylmorphinan derivatives without the 4,5-epoxy ring showed more κ selectivity than those with a 4,5-epoxy ring led us to develop a working hypothesis: the position of the plane composed of the A and B rings would influence the opioid receptor type selectivity and that the decrease in the torsion angle C11-C12-C13-C14 could improve the κ selectivity. Consistent with our hypothesis, KNT-42 with an N-cyclopropylmethyl propellane structure, whose A and B rings were fixed in a torsion angle of approximately 0°, showed κ selective agonist activity. |
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| Keywords: | Opioid Propellane κ Selectivity Torsion angle |
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