Table 5:

Replacement or modification of the pyrrole ring methyl groups

Cmpd	Cmpd ID	X	Y	R	IC50 (μM)			EC50 (μM)
					PfDHODH	PvDHODH	hDHODH	Pf3D7 cellsa
26	DSM501	H	H		2.5 (1.9–3.2)	1.2 (0.94–1.5)	>100	1.7, 0.50
27	DSM503	H	Me		10 ± 0.96 (3)	2.3 (1.5–3.6)	>100	3.6 (3.1–4.2)
28	DSM506	H	Me		>100 (2)	nd	nd	>10
29	DSM507	H	Me		>100	nd	nd	>20
30	DSM511	H	Me		2.8 (2.1–3.8)	nd	nd	1.9 (1.2–3.0)
31	DSM512	H	Me		5.7 (4.4–7.4)	nd	nd	3.5 (2.5 – 4.9)
32	DSM513	H	Me		>100	nd	nd	>10
33	DSM514	H	Me		>100	nd	nd	>10
34	DSM515	H	Me		>100	nd	nd	>10
35	DSM518	H	Me		>100	nd	nd	>20
36	DSM524	H	Me		>100	nd	nd	>20
37	DSM502	Me	H		0.020 ± 0.0054 (7)	0.014 ± 0.0046 (3)	>100 (3)	0.014 ± 0.0055 (6)
38	DSM525	Me	H		0.17 (0.15–0.2)	0.21 (0.17–0.26)	>100	0.082 (0.073–0.093)
39	DSM528	Me	H		0.21 (0.16–0.27)	0.051 (0.043–0.061)	>100	0.044, 0.059
40	DSM529	Me	H		0.080 (0.062–0.1)	0.018 (0.015–0.021)	>100	0.013 (0.011–0.016)
41	DSM530	Me	H		0.11 (0.084–0.15)	0.064 (0.051–0.082)	>100	0.051 (0.029–0.090)
42	DSM531	Me	H		9.8 (7.4–12.8)	nd	nd	4.8 (3.5 – 6.5)
43	DSM532	Me	H		0.098 (0.077–0.12)	0.041 (0.034–0.049)	>100	0.065 ± 0.029 (4)
44	DSM536	Me	H		0.018±0.0021 (3)	0.0075± 0.0031 (3)	>100 (3)	0.0099 ±0.0020 (3)
45	DSM538	Me	H		0.033±0.0079 (3)	0.018 ±0.0025 (3)	>100 (3)	0.029 ± 0.0079 (4)
46	DSM539	Me	H		>100	nd	nd	>100
47	DSM546	Me	H		0.12 (0.11–0.14)	0.2 (0.17–0.25)	>100	0.051 (0.036–0.072)
48	DSM552	Me	H		3.6 (4.0–5.4)	nd	nd	1.3 (0.86–2.0)
49	DSM553	Me	H		0.32 (0.40 – 0.90)	nd	nd	0.17 (0.16–0.19)
50	DSM559	Me	H		9.3 (6.3–12)	nd	nd	3.9 (3.3 – 6.9)
51	DSM560	Me	H		0.044 ±0.19 (3)	0.019 ± 0.0058 (3)	>100 (3)	0.027 (0.023–0.032)
52	DSM534		H		0.45 (0.34–0.6)	0.07 (0.05–0.096)	>100	0.24±0.046 (3)
53	DSM535		H		4.3 (2.5–7.4)	nd	nd	1.2±0.64 (3)
54	DSM526	Me	CF3		1.6 (1.4–1.9)	nd	nd	0.77 (0.60 – 1.0)
55	DSM527	H	Me		>100 (2)	nd	nd	>10
56	DSM533	Me	H		0.88 (0.78–1.0)	0.21 (0.17–0.26)	>100	0.39±0.085 (3)

See Table 1 footnote. nd, not determined