Table 3. Metabolically labile groups can be stabilized as heteroaromatic isosteres. Cox et al.55 used scaffold-hopping to replace a metabolically labile amide by incorporating a metabolically stable 1,3,4-oxadiazole. H/R LM: human/rat liver microsomes.

Compound	X	Y	R1	R2	LM (H, R) % remaining after 30 min
19	—	—	—	—	0, 0
20a	O	CH	Ph	H	73, 29
20b	NH	CH	Ph	H	62, 4
20c	NH	N	Ph	—	78, 29
20d	O	N	Ph	—	82, 0