TABLE 3.

DMDP derivatives with complex ring substitutions attached to the CN bridge  

Derivative no.a	SRI no.b	X	IC50 (nM) for:		Selectivity ratioc
			Human DHFR	MAC DHFR
52	8708d		710	1.9	374
53	8691		142	0.93	153
54	9735		5,300	320	16.6
55	9468		10	0.76	13.2
56	9771		3,400	280	12.1
57	9449		12	1.2	10.0
58	7747e		820	86	9.5
59	9487		6.7	0.86	7.79
60	9450		7.1	0.95	7.47
61	9824		6.2	1.0	6.2
62	7711		4.3	0.81	5.31
63	9825		2.0	0.43	4.65
64	9692		4.0	0.87	4.6
65	9439		4.3	0.98	4.39
66	9823		3.8	0.88	4.3
67	9673		>25,300	620

^aDerivatives are listed in descending order by selectivity ratio (see last column). 

^bSRI, Southern Research Institute. 

^cSelectivity ratio = IC₅₀ human DHFR/IC₅₀ MAC DHFR. 

^d H group on N link is replaced with a CH₃ group. 

^e CH₃ group in position 5 is replaced with an H.