Table 2.

Structure and anti-influenza virus activity of dihydrofuropyridinones with a monocyclic substituent at R³.

Compound	Substituent				EC50a (μM) for influenza virus (S.I.b)			CC50c (μM) for MDCK cells
	X	R1	R2	R3	A/Puerto Rico/8/34	A/Hong Kong/8/68	B/Lee/40
15j	S	H	Me		5.0 ± 1.0 (>180.0)	6.2 ± 3.1 (>145.2)	5.9 ± 2.0 (>152.5)	>900.0
15k	O	H	Me		>19.8	>19.8	>19.8	19.8 ± 8.2
15l	S	H	Ph		>100.0	27.1 ± 5.8	>100.0	>900.0
15m	S	H	Me		21.4 ± 12.6	34.1 ± 10.0	16.3 ± 8.5	>900.0
15n	O	H	Me		>61.9	>61.9	>61.9	61.9 ± 10.7
15o	S	H	Me		>100.0	>100.0	>100.0	>900.0
15p	S	H	Me		>100.0	>100.0	>100.0	>900.0
15q	S	H	Me		7.5 ± 3.2 (>120.0)	6.8 ± 1.3 (>132.4)	7.0 ± 3.8 (>128.6)	>900.0
15r	S	H	Ph		28.9 ± 12.6	15.1 ± 3.8	31.7 ± 19.4	>900.0
15s	S	H	Me		17.6 ± 11.0 (>51.1)	12.7 ± 8.2 (>70.9)	14.0 ± 7.4 (>64.3)	>900.0
15t	S	H	Me		8.0 ± 3.6 (>112.5)	12.2 ± 2.9 (>73.8)	9.6 ± 3.5 (>93.8)	>900.0
15u	S	H	Me		31.7 ± 21.7	32.6 ± 10.2	46.6 ± 28.6	>900.0
15v	S	H	Me		63.7 ± 36.0	47.1 ± 18.7	71.8 ± 22.2	>900.0
15w	S	H	Me		>100.0	>100.0	>100.0	>900.0
15x	S	Me	Me		12.1 ± 9.5 (>74.4)	11.7 ± 2.7 (>76.9)	8.0 ± 3.6 (>112.5)	>900.0
Amantadine hydrochloride					>100.0	2.8 ± 1.7	>100.0	>100.0
Oseltamivir carboxylate					0.03 ± 0.01	<0.01	1.3 ± 0.7	>100.0
T-705d					4.3 ± 2.4	6.5 ± 1.7	6.1 ± 0.6	>100.0
Ribavirin					18.8 ± 4.3	20.2 ± 2.4	23.7 ± 5.4	>100.0

^aEffective concentration required for reducing virus-induced cytopathicity by 50%.

^bSelectivity index, CC₅₀/EC₅₀.

^cCytotoxic concentration required for reducing MDCK cell viability by 50%.

^dFavipiravir.