Synthesis and Biological Activity of the Metabolites of Diethyl 4-[(4-Bromo-2-cyanophenyl)carbamoyl]benzylphosphonate (NO-1886)

• Published in: Chemical & pharmaceutical bulletin Vol. 44; no. 3; pp. 547 - 551
• Main Authors: GOTO, Kiyoto, NAKAMURA, Shizuo, MORIOKA, Yujiro, KONDO, Mitsuyoshi, NAITO, Shinsaku, TSUTSUMI, Kazuhiko
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01-03-1996; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; Benzamides - chemistry; Benzamides - pharmacokinetics; Benzamides - pharmacology; Biological and medical sciences; Biotransformation; Chromatography, High Pressure Liquid; diethyl 4-[(4-bromo-2-cyanophenyl)carbamoyl]benzylphosphonate; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacokinetics; Enzyme Inhibitors - pharmacology; General and cellular metabolism. Vitamins; Hyperlipidemias - blood; Hyperlipidemias - chemically induced; Hyperlipidemias - drug therapy; Lipoprotein Lipase - antagonists & inhibitors; lipoprotein lipase activity; Magnetic Resonance Spectroscopy; Male; Medical sciences; metabolite; Organophosphorus Compounds - chemistry; Organophosphorus Compounds - pharmacokinetics; Organophosphorus Compounds - pharmacology; Pharmacology. Drug treatments; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; synthesis; Triglycerides - blood; Triton WE-1339; Nitrile; Rat; Metabolite; Phosphorus Organic compounds; Structure activity relation; Organic sulfate; Glycoside; Chemical synthesis; Rodentia; Oral administration; Organic phosphonate; Triglyceride; Metabolic disorder; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Treatment; Hypertriglyceridemia; Animal; Uronic acid; Phenols; Carboxamide; Benzenic compound; Antilipemic agent
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.44.547

Five metabolites of diethyl 4-[(4-bromo-2-cyanophenyl)carbamoyl]benzylphosphonate (NO-1886) (1) were synthesized to confirm their proposed structures. The metabolites (2-6) were found to be identical with the synthesized compounds. These metabolites were orally administrated to Triton WR-1339-induced hypertriglyceridemic rats, and the plasma levels of triglycerides were measured to estimate lipoprotein lipase activity. All the metabolites showed lower potency than NO-1886.