. 2024 May 5;25:100546. doi: 10.1016/j.ijpddr.2024.100546

Table 1.

Added molecular groups and activities of 29 robenidine derivatives tested. Activities against NTS and adult S. mansoni are presented after 72 h. EC₅₀ values are shown after 72 h.

Compound	Added molecular groups					NTS		Adult S. mansoni
Compound	R1	R2	R3	R4	X	% Activity 10 μM, (SD)	EC₅₀ [μM]	% Activity 10 μM, (SD)	EC₅₀ [μM]
1	3-CN, 4-F	3-CN, 4-F	H	H	NH	100 (0)	1.25^a	72 (19)	5.46^b
12	4-CF3	4-CF3	H	H	NH	68 (35)	6.23^b	25 (11)
13	4-CF3	4-CF3	CH3	CH3	NH	96 (9)	1.67^b	45 (14)
16	4-OCF3	4-OCF3	H	H	NH	96 (9)	3.31^a	59 (22)	8.06^a
17	4-OCF3	4-OCF3	CH3	CH3	NH	100 (0)	2.01^b	64 (19)	4.91^a
18	4-OCHF2	4-OCHF2	H	H	NH	90 (12)	4.63^b	64 (19)	5.12^a
19	4-OCHF2	4-OCHF2	CH3	CH3	NH	96 (11)	2.79^a	99 (3)	2.78^b
20^ç	2-CN	2-CN	H	H	NH	22 (8)
21	3-CN	3-CN	H	H	NH	98 (7)	1.66^a	79 (14)	4.04^a
23	3-CN	3-CN	CH3	CH3	NH	100 (0)	1.12^b	91 (7)	2.69^b
24^ç	No Substitution	No Substitution	H	H	NH	22 (18)
26	4-Phenyl	4-Phenyl	H	H	NH	76 (8)	4.43^a	9 (10)
27	4-NO2	4-NO2	H	H	NH	63 (13)	5.71^a	32 (13)
32	4-Propynoxy	4-Propynoxy	H	H	NH	62 (15)	5.12^a	49 (10)
33	4-Morpholino	4-Morpholino	H	H	NH	83 (20)	2.44^b	60 (15)	6.45^a
37	2, 4-OCH3, 5-Cl	2, 4-OCH3, 5-Cl	CH3	CH3	NH	100 (0)	2.7^a	49 (14)
39^ç	4-OCF3	4-OCF3	H	H	O	19 (15)
49	3-NO2	3-NO2	H	H	NH	100 (0)	3.3^a	76 (14)	9.47^b
52	3-Phenyl	3-Phenyl	H	H	NH	75 (21)	3.09^b	52 (22)	7.57^b
53	4-Phenyl, 4′-F	4-Phenyl, 4′-F	H	H	NH	90 (11)	3.37^a	22 (16)
57	4-Ophenyl	4-Ophenyl	H	H	NH	100 (0)	3.84^b	66 (15)	7.07^a
58	4-Ophenyl, 4′-F	4-Ophenyl, 4′-F	H	H	NH	100 (0)	4.51^b	56 (17)	8.59^a
59	4-Ophenyl, 4′-Cl	4-Ophenyl, 4′-Cl	H	H	NH	100 (0)	2.7^a	75 (6)	5.52^a
62	2-Quinoline	2-Quinoline	H	H	NH	90 (26)	2.5^b	54 (17)	7.49^b
63	3-Quinoline	3-Quinoline	H	H	NH	96 (9)	0.65^a	39 (11)
64	4-Quinoline	4-Quinoline	H	H	NH	93 (11)	1.57^b	34 (11)
71	3-CN, 4-Cl	3-CN, 4-Cl	H	H	NH	100 (0)	1.24^a	47 (15)
77	4-OCF3	3-CN, 4-F	H	H	NH	63 (16)	4.02^a	68 (18)	6.76^a
86	4-BnCOBn	4-Propynoxy	H	H	NH	78 (14)	4.44^a	45 (15)

Compounds marked with ^ç did not reached significant activity in NTS but give insights regarding the SAR. Blank cells = data not available. All concentrations were tested in duplicates and the corresponding experiments were repeated once.

EC₅₀ values obtained by applying a nonlinear least-squares analysis using a four-parameter sigmoid function.

EC₅₀ values obtained by applying a nonlinear least-squares analysis using a two-parameter sigmoid function.