Studies on antianaphylactic agents. 6. Synthesis of some metabolites of 6-ethyl-3-(1H-tetrazol-5-yl)chromone and their analogs

• Published in: Journal of medicinal chemistry Vol. 22; no. 3; pp. 290 - 295
• Main Authors: Nohara, Akira, Kuriki, Hisashi, Ishiguro, Toshihiro, Saijo, Taketoshi, Ukawa, Kiyoshi, Maki, Yoshitaka, Sanno, Yasushi
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.03.1979
• Subjects: Animals; Chemical Phenomena; Chemistry; Chromones - chemical synthesis; Chromones - pharmacology; Male; Passive Cutaneous Anaphylaxis - drug effects; Rats; Tetrazoles - chemical synthesis; Tetrazoles - pharmacology
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00189a014

The metabolites of 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) (1), an orally effective antiallergic agent, and their analogues were synthesized to confirm the proposed structures and to determine their activity in the rat passive cutaneous anaphylaxis (PCA) test. A glucuronic acid metabolite (6) was assigned the structure 24b, 1-deoxy-1-[5-(6-ethylchromon-3-yl)tetrazol-1-yl]-beta-D-glucopyranuronate, by the comparison of 13C NMR, mass spectra, and TLC of isomeric compounds. In 13C NMR spectra, the shift difference of the tetrazole ring carbons between a pair of isomers was more remarkable than that of the glycosidic carbons. Therefore, the former is a useful criterion for distinguishing between such isomers. Some of the metabolities and analogues were active when administered intravenously, and two metabolites (2 and 3) were also effective upon oral administration.