TABLE 5.

DMDP derivatives in the series involving substitutions at the R2 and R5 positions  

Derivative no.a	SRI no.b	Substitution at position		MICc of MAC (μg/ml)	IC50 (nM) for:		Selectivity ratiod
		R2	R5		Human DHFR	MAC DHFR
15	9018	CH3	CH3	++++	57	0.92	62
7	8229	OCH3	CH3	++++	300	0.86	349
4	8202	CH3	OCH3	++++	150	0.40	375
2	8117	OCH3	OCH3	++++	1,000	1.1	909
1	8686	OCH2CH3	OCH2CH3	++++	2,300	0.84	2,738
78	20094	O(CH2)2CH3	O(CH2)2CH3	++++	7,300	1.0	7,300

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

^bSRI, Southern Research Institute. 

^c++++, ≤0.13. MAC strain NJ3440 was used for comparison of MIC. 

^dSelectivity ratio equals IC₅₀ human DHFR/IC₅₀ MAC DHFR.