Structural reassignment of a dibenz[

• DOI: 10.1071/ch22184
• Publication Date: 2022-11-10T06:07:11Z
• Authors: Andrew G. Riches; Christopher J. S....; Matthieu Schmit; Emmanuel A. Debele; Snigdha Tiash; Erin Clapper; Tina S. Skinner-A...; John H. Ryan
• Keywords: 0301 basic medicine; 03 medical and health sciences

A screen for compounds with antigiardial activity in the Compounds Australia Scaffolds library identified SN00797640 (supplied structure being 8-acylaminodibenzoxazepinone 1) as a hit compound with potent anti-parasitic activity (concentration for 50% growth inhibition of Giardia duodenalis, IC50 0.18 μM). To further explore the structure–activity relationships in this series, compound 1 and analogues, including its 7-acylaminodibenzoxazepinone regioisomer (2), were synthesized and assessed for anti-Giardia activity. While regioisomer 2 demonstrated antigiardial activity, resynthesized 1 and other 8-acylaminodibenzoxazepinone analogues were inactive. Comparison of spectroscopic and physical properties demonstrated the correct structure of SN00797640 to be 7-acylamino regioisomer 2. These results highlight the importance of independent synthesis in verifying the structure and activity of screening hits.