Table 2.

Initial analog series from hit compound 4.

Compound	X	R	R′	Yield from 16a/b, %	ELISA inhibition	Estimated IC50/nM
4	NO2	CO2H	H	80	10 nM∗∗	22.7
4a	NO2	CO2Et	H	84	100 nM ∗∗∗	13.9
4b	NO2	F	H	81	100 nM∗	ND
4c	NO2	Cl	H	82	–
4d	NO2	NO2	H	93	–
4e	NO2	H	H	72	–
4f	NO2	H	CO2H	80	<10 nM∗∗∗	0.482
4g	NO2	H	CO2Et	78	–
4h	NO2	H	F	88	–
4i	NO2	H	Cl	91	–
4j	NO2	H	NO2	78	–
4k	NO2	H	I	84	–
4l	NO2	H	t-Bu	82	-
4m	H	CO2H	H	95	–
4n	H	CO2Et	H	96	–
4o	H	F	H	87	10 nM∗	1.30
4p	H	Cl	H	92	–
4q	H	NO2	H	95	–
4r	H	H	H	83	10 nM∗	0.796
4s	H	H	CO2H	86	–
4t	H	H	CO2Et	92	–
4u	H	H	F	96	10 nM∗	4.15
4v	H	H	Cl	94	–
4w	H	H	NO2	83	–
4x	H	H	I	89	–
4y	H	H	t-Bu	93	-

Statistical significance by one-way ANOVA, ∗ = p < 0.05, ∗∗ = p < 0.01, ∗∗∗ = p < 0.001.

- = no significant inhibition below 1 μM, ND = not determined.