Synthesis approach and biological activity evaluation of a series of 1,3,2-oxazaphosphole-2-oxides against inflammation and nociception

• Published in: Monatshefte für Chemie Vol. 150; no. 2; pp. 283 - 294
• Main Authors: Abdou, Wafaa M., Sabry, Eman, Shaddy, Abeer A.
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.02.2019; Springer Nature; Springer Nature B.V
• Subjects: Analytical Chemistry; Biological activity; Chemistry; Chemistry and Materials Science; Chemistry, Multidisciplinary; Chemistry/Food Science; Ibuprofen; In vivo methods and tests; Inorganic Chemistry; Lipophilicity; Organic Chemistry; Original Paper; Pharmacology; Physical Chemistry; Physical Sciences; Science & Technology; Substrates; Theoretical and Computational Chemistry; Lipophilicity measurement; Antiinflammation; Antinociception; Substituted 1,3,2-oxazaphosphole-2-oxides synthesis; DRUG; CATALYSIS; ANTIINFLAMMATORY ACTIVITY; HETEROCYCLES; MECHANISMS; BINDING-ENERGY; INHIBITORS
• ISSN: 0026-9247; 1434-4475
• DOI: 10.1007/s00706-018-2312-x

In the present work, we synthesized a series of substituted benzoxazaphosphole-2-oxides in high yields (68–84%). The approach involved the preparation of oxazaphospholo-2-oxide monochloride, which is the key substrate, followed by its treatment with amino-, hydroxyl-, and thiolocompounds under mild conditions to afford the corresponding cyclophosphamide, cyclophosphamidate, and cyclophosphathioamidate groups as target products. Lipophilicity prediction and in vivo antinociceptive and antiinflammatory properties of new molecules were determined. Out of 14 tested compounds, the most hydrophobic compounds were found to be also of the highest antinociceptive and the antiinflammatory effects compared with reference drugs ibuprofen and indomethacin. The pharmacological results also showed that three candidates from the cyclophosphamide group are more active as antiinflammatory agents than the reference drug at all the successive time intervals. Graphical abstract