Structural reassignment of a dibenz[b,f][1,4]oxazepin-11(10H)-one with potent antigiardial activity.

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. A screen of commercially available compounds against the intestinal parasite Giardia duodenalis yielded several dibenz[ b,f ][1,4]oxazepin-11(10 H)-one hits, of which the most potent (0.180 mM) was designated by the vendor as structure 1. However, independently synthesized 1 lacked antigiardial activity. Synthesis of the regioisomer 2 revealed it to be the true structure of the assay hit. [ABSTRACT FROM AUTHOR]