TABLE 4.

Inhibition of E. coli DHFR by di- and tricyclic diaminopyrimidines

Compound	IC50 (μM)a
Trimethoprim	0.012 ± 0.003
I.1	0.026 ± 0.0076
I.2	0.036 ± 0.015
I.3	1.2 ± 0.44
I.4	3.1 ± 1.5
I.5	0.30 ± 0.064
I.6	3.1 ± 2.6
I.7	0.23 ± 0.27
II.2	0.00053 ± 0.0022
II.3	<0.0001
II.4	0.0029 ± 0.0029
II.5	0.024 ± 0.017
II.6	0.059 ± 0.044
III.1	0.0084 ± <0.001
III.2	0.0061 ± 0.0025
III.3	0.00045 ± <0.0002
III.4	0.012 ± 0.0024
III.5	0.00011 ± <0.00002
III.6	<0.0001
IV.1	0.0034 ± 0.0028
IV.2	0.046 ± 0.015
IV.3	0.087 ± 0.010
IV.4	8.5 ± 2.5
IV.5	0.21 ± 0.088
IV.6	0.28 ± <0.0001
IV.7	0.068 ± 0.00887
IV.8	3.1 ± 0.68
IV.9	7.5 ± 2.2
IV.19	4.5 ± 2.6
IV.11	7.9 ± 1.8
IV.12	2.0 ± 1.3
IV.13	<0.0001
IV.14	0.00014 ± <0.0001
IV.15	1.5 ± 0.20
IV.16	1.1 ± 0.16
IV.17	<0.0001
IV.18	0.00012 ± <0.0001
V.1	0.041 ± 0.014
V.2	0.00084 ± <0.0004
V.3	0.080 ± 0.020
V.4	0.011 ± 0.0020
V.5	0.0014 ± 0.0011
V.6	0.0036 ± 0.0016
V.7	0.0066 ± 0.0013
V.8	0.00054 ± 0.00025
V.9	0.0011 ± 0.0010
V.10	0.00016 ± 0.00012
V.11	0.0019 ± 0.00026
V.12	0.0030 ± 0.00080
V.13	0.00052 ± 0.00032
V.14	0.00025 ± 0.00026
V.15	0.0021 ± 0.0016
V.16	0.00024 ± 0.00012
VI.3	0.0036 ± <0.001
VI.4	0.031 ± 0.016
VI.5	0.018 ± 0.0052
VI.6	0.075 ± 0.015
VI.7	0.031 ± 0.019
VI.12	0.0075 ± 0.,0023
VII.1	0.097 ± 0.031
VII.4	3.3 ± 1.1
VIII.1	1.8 ± 0.60
VIII.2	0.19 ± 0.025
VIII.3	0.18 ± 0.060
VIII.6	0.0035 ± 0.0013
VIII.7	0.0077 ± 0.012
VIII.8	0.032 ± 0.00565
VIII.9	0.087 ± 0.052
VIII.10	0.62 ± 0.33
IX.1	0.012 ± 0.0044
IX.2	0.026 ± 0.014
IX.3	0.018 ± 0.0064
IX.4	0.011 ± 0.0056

^aThe values shown are the means ± the standard deviations of several determinations. Compounds VI.9 and VI.12 to VI.17 are not listed because their IC₅₀s were >10 μM. Compounds I.8, II.1, VI.1, VI.2, VI.10, VII.2, and VII.3 were not tested. Structures are shown in Fig. 2.