title: Identification of urinary metabolites of 2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine in rat, rabbit and dog.
abstract: The metabolism of KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine, CAS 94457-09-7) in rat, rabbit and dog was studied. The urine of animals dosed with 14C-KC-764 was extracted with ethyl acetate after treatment with beta-glucuronidase and arylsulfatase. The metabolites were purified by TLC and HPLC from the extract. Unchanged KC-764 and 16 metabolites were isolated and their structures were identified or proposed by NMR and MS spectrometry. The metabolism of KC-764 took place by the oxidation of the tetrahydropyridine ring, 6,7-position and 2-methyl group of the pyrazolopyridine ring, and their combinations. The oxidation of the tetrahydropyridine ring was predominant in dog, whereas the oxidation of the pyrazolopyridine ring was more important in rabbit. Rat produced the various metabolites by their combination. 6-Oxo and 6-ureido derivatives of the tetrahydropyridine ring were common major metabolites in all animal species studied.
authors.affiliation: Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd., Tochigi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Komuro
authors.forename: R
authors.initials: R
authors.lastname: Ishida
authors.forename: H
authors.initials: H
authors.lastname: Uchida
mesh_terms: D000818:Animals; D001711:Biotransformation; D001643:Bridged Bicyclo Compounds / Q000493:pharmacokinetics / Q000652:urine*; D002855:Chromatography, Thin Layer; D004285:Dogs; D008401:Gas Chromatography-Mass Spectrometry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009539:Nicotinic Acids / Q000493:pharmacokinetics / Q000652:urine*; D010084:Oxidation-Reduction; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000652:urine*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013056:Spectrophotometry, Ultraviolet
chemical_list: D001643:Bridged Bicyclo Compounds; D009539:Nicotinic Acids; D010975:Platelet Aggregation Inhibitors; C074536:KC 764