Table 3. Analogs Designed To Overcome the Permeability Challenge.

ID	R1	R2	R3	R4	R5	O. volvulus IC50 (μM) or % inhibition of molting at 1 μM	G2/M IC50 (μM)	MDCK-MDR1 Papp (A-B, ×106 cm/s)
8a	H	H	H	H	H	0.300	13	0.8
8e	CH3	H	H	H	H	24%a	>100	1.2
8f	H	H	CH3	H	H	29%a	>100	1.8
8g	H	CH3	H	H	H	NT	4.1	0.6
8h	H	CH2CH2NMe2	H	H	H	NT	35	0.14
8i	H	H	H	F	H	0%a	16	2.35
8j	H	H	H	H	F	0.13	1.26	2.83

^a% of O. volvulus larvae that completed molting from L3 to L4 compared to control worms.