TABLE 1.

Activity in influenza A/H3N2 virus-infected MDCK cells^a

Compoundb	R	R1	R2	Antiviral EC50c (μM)				Cytotoxicityd
				A/X-31		A/HK/7/87		MCC (μM)	CC50 (μM)	IC50 (μM)
				CPE	MTS	CPE	MTS
Series I
3a	Me	H	H	>100	>100	>100	>100	>100	ND	ND
3b	Et	H	H	>100	>100	>100	>100	>100	ND	ND
3c	Phe	H	H	>100	>100	>100	>100	≥100	ND	ND
4a	H	H	Me	100	100	>100	>100	>100	ND	ND
4b	H	Me	Me	32 ± 17	44	42 ± 4	40	>100	ND	ND
4c	Me	H	Me	3.3 ± 1.3	3.2 ± 2.0	5.0 ± 2.3	3.2 ± 2.3	≥100	>100	93
4d	Et	H	Me	2.4 ± 2.1	4.0 ± 3.8	4.2 ± 3.3	4.3 ± 3.0	50	>50	48
4e	Phe	H	Me	>100	>100	>100	>100	100	ND	ND
Series II
2a	Me			>100	>100	>100	>100	≥100	ND	ND
2b	Et			>100	>100	>100	>100	>100	ND	ND
2c	Phe			>100	>100	>100	>100	>100	ND	ND
Series III
6a	Me		H	>300	>300	>300	>300	≥60	>300	ND
6b	Me		Me	2.6 ± 2.3	5.9 ± 4.3	2.8 ± 1.8	1.4 ± 0.6	>50	>50	38
Oseltamivir carboxylate				0.0042 ± 0.0035	0.020 ± 0.040	1.7 ± 1.9	0.63 ± 0.23	>100	>100	80
Ribavirin				9.9 ± 3.3	11 ± 4	7.4 ± 2.1	7.2 ± 3.8	61 ± 30	>100	18

^aThe data shown are the means ± standard deviations of 2 to 7 independent tests. ND, not done. MDCK cells, Madin-Darby canine kidney cells; Et, ethyl; Me, methyl; Phe, phenyl.

^bFigure 1 shows the basic structures of the N-(1-thia-4-azaspiro[4.5]decan-4-yl)carboxamide compounds, series I, II, and III.

^cAntiviral activity is expressed as the EC₅₀, defined as the compound concentration producing 50% inhibition of virus replication, as estimated by microscopic scoring of the CPE or by measuring cell viability in the formazan-based MTS assay.

^dCytotoxicity is expressed as the MCC, the compound concentration producing minimal changes in cell morphology, as estimated by microscopy; the CC₅₀, estimated by the MTS cell viability assay; or the IC₅₀, determined by cell counting.