Synthesis and Anti-inflammatory Activity of Steroidal 17-Yl-α-Oxothiocarboxamides and Related Compounds

• Published in: Chemical & pharmaceutical bulletin Vol. 27; no. 6; pp. 1352 - 1359
• Main Authors: OBAYASHI, MIKIHIKO, KUZUNA, SEIJI, NOGUCHI, SHUNSAKU
• Format: Journal Article
• Language: English
• Published: The Pharmaceutical Society of Japan 1979
• Subjects: anti-inflammatory activity
• DOI: 10.1248/cpb.27.1352
• ISSN: 0009-2363

The Willgerodt-Kindler reaction of 21-chloro-20-ketosteroids (5) or sodium 21-thiosulfate derivatives of 20-ketosteroids (6) with sulfur in secondary amines gave the corresponding steroidal α-oxothiocarboxamides (3) in good yields. Among these compounds (3), 11β, 17α-dihydroxy-21-morpholinopregna-1, 4-diene-3, 20-dione-21-thione (3a) and 11β, 17α-dihydroxy-21-morpholinopregn-4-ene-3, 20-dione-21-thione (3b) showed potent anti-inflammatory activities comparable to or a little less than those of the parent compounds, prednisolone and hydrocortisone, respectively, in the carrageenin edema test in rats. 3a also showed potent activity in the granuloma pouch test in rats but much less activity in the cotton pellet test in rats. These results suggest that 3a might be more active against acute or subacute inflammation than against chronic inflammation.