Benzimidazole-based derivatives as privileged scaffold developed for the treatment of the RSV infection: a computational study exploring the potency and cytotoxicity profiles

Figures & data

Figure 1. General structures of benzimidazole-based anti-RSV agents

Scheme 1. Reagents and conditions: (a) 120 °C, 9 h; (b) SnCl₂ . 2H₂O, conc. HCl, EtOH, 6 h at reflux; (c) 180°, N₂, 90 min.

Table 1. Chemical structure of benzimidazoles 1–156* and the related anti-RSV potency and cytotoxicity profiles (evaluated against MT-4 and VERO-76 cell lines)

Comp.	R1	R2	R3	R4	RSV pEC50	MT-4 pCC50	VERO-76 pCC50
1		–CH3	–CF3	–H	<4.00	4.00	4.00
2		–CF3	–CF3	–H	4.66	4.27	4.00
3	-H		–H	–H	<4.00	4.00	4.00
4			–CF3	–H	<4.00	4.96	4.00
5	–H		–H	–H	<4.00	4.00	4.00
6	–H		–CF3	–H	< 4.00	4.00	4.15
7	–H		–CF3	–H	<4.00	4.16	4.04
8	–H		–CF3	–H	<4.00	4.00	4.00
9	–C4H9(n)		–CF3	–H	5.05	4.00	4.00
10	–CH2CH2OCH3		–CF3	–H	<4.00	4.00	4.00
11	–H		–Cl	–Cl	5.30	4.54	4.00
12	–H		–Cl	–Cl	4.70	4.15	4.10
13	–(CH2)2N(C2H5)2		–H	–H	<4.00	4.38	4.00
14	–(CH2)2N(C2H5)2		–H	–H	4.12	4.31	4.00
15	–(CH2)2N(C2H5)2		–H	–H	4.40	4.60	4.00
16	–(CH2)2N(CH3)2		–CF3	–H	<4.00	4.00	4.00
17	–(CH2)3N(C2H5)2		–CF3	–H	<4.00	4.40	4.00
18			–CF3	–H	<4.00	4.00	4.03
19			–CF3	–H	<4.00	4.00	4.00
20			–CF3	–H	4.82	5.22	4.00
21			–CF3	–H	4.60	4.89	4.00
22			–Cl	–Cl	<4.00	4.77	4.00
23			–Cl	–Cl	4.92	5.05	4.00
24			–Cl	–Cl	5.05	4.92	4.00
25	–H		–H	–H	4.40	4.22	4.00
26	–H		–H	–H	<4.00	5.15	4.00
27	–H		–CF3	–H	4.70	4.77	4.00
28	–H		–CF3	–H	<4.82	5.70	4.82
29	–H		–CF3	–H	5.15	4.72	4.00
30	–H		–CF3	–H	4.00	4.00	4.00
31	–H		–CF3	–H	5.00	4.72	4.00
32	–H		–CF3	–H	<4.15	4.03	4.15
33	–H		–CF3	–H	<4.54	5.40	4.54
34	–H		–CF3	–H	<4.07	4.70	4.07
35	–H		–CF3	–H	<4.30	5.30	4.30
36	–H		–CF3	–H	<4.35	5.22	4.35
37	–H		–CF3	–H	<4.60	5.05	4.60
38	–H		–CF3	–H	<4.22	4.66	4.22
39	–H		–CF3	–H	<4.60	4.00	4.60
40	–H		–NO2	–H	<4.00	4.00	4.00
41	–H		–NO2	–H	<4.00	4.00	4.00
42	–H		–COCH3	–H	<.00	4.00	4.00
43	–H		–COCH3	–H	<4.00	4.00	4.00
44	–H		–Cl	–Cl	5.15	4.92	4.74
45	–H		–Cl	–Cl	<4.52	6.00	4.52
46	–H		–Cl	–Cl	<4.10	5.70	4.10
47	–H		–Cl	–Cl	<4.12	5.52	4.12
48	–H		–Cl	–Cl	<4.00	4.77	4.00
49	–H		–Cl	–Cl	<4.00	4.77	4.00
50	–H		–H	–H	n.d	4.00	4.00
51	–H		–H	–H	n.d	4.00	4.00
52	–H		–H	–H	n.d	4.46	4.00
53	–H		–H	–H	n.d	4.40	4.00
54	–H		–H	–H	n.d	4.51	4.00
55	–H		–H	–H	n.d	4.00	4.00
56	–H		–H	–H	n.d	4.74	4.10
57	–H		–CF3	–H	n.d	4.21	4.00
58	–H		–CF3	–H	n.d	4.72	4.30
59	–H		–CF3	–H	n.d	4.00	4.00
60	–H		–CF3	–H	n.d	5.30	4.46
61	–H		–CF3	–H	n.d	4.82	4.35
62	–H		–CF3	–H	n.d	5.10	4.62
63	–H		–CF3	–H	n.d	4.74	4.00
64	–H		–CF3	–H	n.d	5.22	4.51
65	–H		–CF3	–H	n.d	4.00	4.00
66	–H		–CF3	–H	n.d	5.00	4.00
67	–H		–CF3	–H	n.d	6.05	4.00
68	–H		–CF3	–H	n.d	5.40	4.40
69	–H		–CF3	–H	n.d	4.00	4.00
70	–H		–NO2	–H	n.d	4.00	4.00
71	–H		–NO2	–H	n.d	4.00	4.00
72	–H		–Cl	–Cl	n.d	4.77	4.00
73	–H		–Cl	–Cl	n.d	4.00	4.00
74	–H		–Cl	–Cl	n.d	5.10	4.00
75	–H		–Cl	–Cl	n.d	4.27	4.00
76	–H		–Cl	–Cl	n.d	4.74	4.00
77	–H		–Cl	–Cl	n.d	4.00	4.00
78	–H		–Cl	–Cl	n.d	4.96	4.00
79	–CH3		–CF3	–H	n.d	4.70	4.00
80	–CH3		–CF3	–H	n.d	4.82	4.00
81	–CH3		–CF3	–H	n.d	5.10	4.00
82	–CH3		–CF3	–H	n.d	5.04	4.05
83	–CH3		–CF3	–H	n.d	4.80	4.00
84	–CH3		–CF3	–H	n.d	5.05	4.00
85	–CH3		–CF3	–H	n.d	4.00	4.00
86	–CH3		–CF3	–H	n.d	5.00	4.00
87	–CH3		–CF3	–H	n.d	4.66	4.00
88	–CH3		–CF3	–H	n.d	5.82	4.52
89			–CF3	–H	n.d	4.36	4.00
90			–CF3	–H	n.d	4.62	4.52
91			–CF3	–H	n.d	4.77	4.00
92			–CF3	–H	n.d	4.72	4.22
93			–CF3	–H	n.d	4.55	4.00
94			–CF3	–H	n.d	4.07	4.00
95			–CF3	–H	n.d	6.52	4.00
96			–CF3	–H	n.d	4.00	4.00
97	–CH3		–CF3	–H	< 4.00	4.00	4.00
98			–CF3	–H	<4.00	4.31	4.00
99			–H	–H	<4.00	4.48	4.00
100			–H	–H	5.15	4.38	4.00
101			– H	–H	<4.00	4.00	4.00
102			– H	–CH3	4.20	4.00	4.00
103			– H	–Cl	4.35	4.25	4.05
104			– Cl	–H	<4.00	4.00	4.00
105			–H	–Cl	<4.00	4.00	4.00
106			–CF3	–H	<4.62	4.62	4.62
107			–CF3	–H	<4.00	4.24	4.00
108			–CF3	–H	<4.11	4.68	4.11
109			–Cl	–Cl	<.12	4.60	4.12
110			–Cl	–Cl	<4.00	4.38	4.00
111	–C4H9(n)		–CF3	–H	<4.10	4.00	4.10
112	–CH2-C6H5		–H	–H	4.60	4.33	4.06
113	–H		–H	–H	<4.00	4.77	4.00
114	–(CH2)2N(CH3)2		–H	–H	6.15	4.00	4.00
115	–(CH2)2N(C2H5)2		–H	–H	5.64	4.00	4.00
116	–(CH2)3N(C2H5)2		–H	–H	6.15	4.00	4.00
117			–H	–H	6.15	4.00	4.00
118			–H	–H	6.52	4.04	4.00
119			–H	–H	6.82	4.19	4.00
120	–(CH2)2N(CH3)2		–Cl	–H	7.52	4.00	4.00
121	–(CH2)2N(C2H5)2		–Cl	–H	6.15	4.00	4.00
122	–(CH2)3N(CH3)2		–Cl	–H	7.22	4.00	4.00
123	–(CH2)3N(C2H5)2		–Cl	–H	7.00	4.30	4.00
124			–Cl	–H	6.05	4.43	4.22
125			–Cl	–H	7.30	4.44	4.06
126			–Cl	–H	7.70	4.80	4.35
127	–(CH2)2N(CH3)2		–CF3	–H	5.00	4.00	4.00
128	–(CH2)2N(C2H5)2		–CF3	–H	5.15	4.00	4.00
129	–(CH2)3N(C2H5)2		–CF3	–H	5.72	4.30	4.00
130			–CF3	–H	<4.44	4.04	4.44
131	–(CH2)2N(CH3)2		–NO2	–H	5.05	4.00	4.00
132	–(CH2)2N(C2H5)2		–NO2	–H	4.96	4.00	4.00
133			–NO2	–H	4.64	4.41	4.08
134	–(CH2)2N(CH3)2		–COCH3	–H	5.74	4.00	4.00
135	–(CH2)2N(C2H5)2		–COCH3	–H	5.15	4.00	4.00
136	–(CH2)3N(C2H5)2		–COCH3	–H	5.92	4.10	4.00
137			–COCH3	–H	5.60	4.11	4.10
138	–(CH2)3N(C2H5)2		–H	–H	5.82	4.00	4.00
139			–H	–H	6.15	4.00	4.00
140			–H	–H	5.92	4.03	4.00
141			–H	–H	7.00	4.15	4.00
142	–(CH2)2N(CH3)2		–Cl	–H	6.52	4.00	4.00
143	–(CH2)2N(C2H5)2		–Cl	–H	6.40	4.10	4.00
144	–(CH2)3N(CH3)2		–Cl	–H	5.82	4.00	4.00
145	–(CH2)3N(C2H5)2		–Cl	–H	6.22	4.15	4.00
146			–Cl	–H	6.00	4.30	4.30
147			–Cl	–H	6.22	4.30	4.12
148			–Cl	–H	7.52	4.52	4.00
149	–(CH2)2N(CH3)2		–CF3	–H	5.60	4.00	4.00
150	–(CH2)2N(C2H5)2		–CF3	–H	5.70	4.05	4.00
151			–CF3	–H	4.96	4.40	4.10
152	–(CH2)2N(CH3)2		–NO2	–H	< 4.00	4.22	4.00
153	–(CH2)2N(C2H5)2		–NO2	–H	<4.00	4.00	4.00
154			–NO2	–H	<4.10	4.35	4.10
155	–(CH2)2N(C2H5)2		–COCH3	–H	4.70	4.00	4.00
156			–COCH3	–H	5.60	4.39	4.10

* All the listed compounds have been previously described16–18.

Table 2. Summary of CoMFA and CoMSIA analyses calculated as model A and B.

	Model A		Model B
	CoMFA	CoMSIA	CoMFA	CoMSIA
No. compounds	50	50	123	123
Optimal number of components (ONC)	5	5	8	8
Leave one out r^2 (r^2loo)	0.653	0.725	0.612	0.641
Cross validated r^2 (r^2cv)	0.703	0.710	0.726	0.712
Std. error of estimate (SEE)	0.279	0.305	0.161	0.196
Non-cross validated r^2 (r^2ncv)	0.92	0.89	0.91	0.87
F value	90.457	57.341	128.631	82.855
Steric contribution	0.574	0.131	0.597	0.151
Electrostatic contribution	0.426	0.203	0.403	0.196
H-bond acceptor contribution	–	0.208	–	0.156
H-bond donor contribution	–	0.235	–	0.238
Hydrophobicity contribution	–	0.2223	–	0.260
Bootstrap r^2 (r^2boot)	0.980	0.943	0.981	0.975
Standard error of estimate r^2boot (SEE r^2boot)	0.210	0.232	0.267	0.269
Test set r^2 (r^2pred)	0.88	0.88	0.63	0.56

Table 3. Model A CoMFA and CoMSIA analyses experimental and predicted pEC₅₀ values of the training set compounds.

		CoMFA model		CoMSIA model
Compound	Exp. pEC50	Pred. pEC50	Residual	Pred. pEC50	Residual
2	4.66	4.94	−0.28	4.247	0.41
9	5.05	5.28	−0.23	5.211	−0.16
11	5.30	5.05	0.25	5.375	−0.08
12	4.70	4.68	0.02	4.544	0.16
14	4.12	4.17	−0.04	4.058	0.06
15	4.40	4.18	0.22	4.049	0.35
21	4.60	4.78	−0.18	4.745	−0.15
23	4.92	5.05	−0.13	5.143	−0.22
25	4.40	4.71	−0.31	4.422	−0.02
27	4.70	4.64	0.06	4.968	−0.27
29	5.15	5.09	0.06	4.703	0.45
30	4.00	4.07	−0.07	4.12	−0.12
31	5.00	5.12	−0.12	4.838	0.16
44	5.15	4.85	0.30	5.289	−0.14
100	5.15	4.97	0.18	5.154	0.00
102	4.20	3.96	0.24	4.135	0.07
114	6.15	6.56	−0.41	6.441	−0.29
115	5.64	5.66	−0.02	6.116	−0.48
116	6.15	6.46	−0.31	6.535	−0.39
117	6.15	5.87	0.28	6.084	0.07
118	6.52	6.78	−0.26	6.532	−0.01
119	6.82	7.08	−0.26	7.064	−0.24
120	7.52	6.98	0.54	6.798	0.72
122	7.22	6.98	0.25	6.798	0.42
123	7.00	6.90	0.10	6.772	0.23
124	6.05	6.26	−0.21	6.421	−0.37
125	7.30	7.22	0.08	6.923	0.38
126	7.70	7.54	0.16	7.45	0.25
127	5.00	5.32	−0.32	5.906	−0.91
128	5.15	4.69	0.46	5.562	−0.41
129	5.72	5.54	0.18	5.307	0.41
131	5.05	5.07	−0.02	5.098	−0.05
132	4.96	4.80	0.16	4.798	0.16
133	4.64	4.87	−0.23	4.641	0.00
134	5.74	5.67	0.07	5.314	0.43
136	5.92	5.99	−0.07	5.756	0.16
138	5.82	5.77	0.05	5.624	0.20
139	6.15	5.68	0.47	5.852	0.30
140	5.92	5.71	0.21	5.909	0.01
141	7.00	7.12	−0.12	7.34	−0.34
143	6.40	6.56	−0.16	6.023	0.38
145	6.22	6.42	−0.20	6.017	0.20
146	6.00	6.08	−0.08	6.144	−0.14
149	5.60	5.02	0.59	5.453	0.15
150	5.70	5.28	0.42	5.356	0.34
151	4.96	5.14	−0.18	5.573	−0.61
152	4.00	4.73	−0.73	4.64	−0.64
153	4.00	4.39	−0.39	4.502	−0.50
155	4.70	5.00	−0.30	4.907	−0.21
156	5.60	5.52	0.08	5.113	0.49

Table 4. Model A CoMFA and CoMSIA analyses experimental and predicted pEC₅₀ values of the test set compounds.

		CoMFA model		CoMSIA model
Compound	Exp. pEC50	Pred. pEC50	Residual	Pred. pEC50	Residual
20	4.82	4.99	−0.17	4.75	0.07
24	5.05	4.91	0.14	5.08	−0.03
103	4.35	3.90	0.45	4.04	0.31
112	4.60	4.77	−0.17	4.39	0.21
121	6.15	5.87	0.28	6.48	−0.32
135	5.15	4.95	0.20	4.98	0.17
137	5.60	5.93	−0.33	5.18	0.42
142	6.52	5.97	0.55	5.95	0.57
144	5.82	6.32	−0.50	6.29	−0.47
147	6.22	6.12	0.10	6.19	0.03
148	7.52	7.68	−0.16	7.76	−0.24

Table 5. Model B CoMFA and CoMSIA analyses experimental and predicted pCC₅₀ values of the training set compounds.

		CoMFA model		CoMSIA model
Compound	Exp. pCC50	Pred. pCC50	Residual	Pred. pCC50	Residual
2	4.27	4.41	−0.14	4.56	−0.29
3	4.00	3.85	0.15	3.92	0.08
4	4.96	5.13	−0.17	4.85	0.12
6	4.00	4.06	−0.06	4.12	−0.12
7	4.16	4.09	0.07	4.16	0.00
8	4.00	3.90	0.11	3.86	0.14
9	4.00	3.98	0.02	3.96	0.04
10	4.00	3.87	0.13	3.92	0.08
11	4.54	4.37	0.17	4.48	0.06
12	4.15	4.38	−0.23	4.17	−0.02
13	4.38	4.34	0.04	4.15	0.23
14	4.31	4.38	−0.07	4.23	0.08
15	4.60	4.36	0.24	4.37	0.23
16	4.00	3.97	0.03	4.30	−0.30
17	4.40	4.29	0.11	4.39	0.01
18	4.00	4.21	−0.21	4.07	−0.07
20	5.22	4.96	0.26	4.72	0.50
22	4.77	5.03	−0.26	5.00	−0.23
23	5.05	4.84	0.21	4.92	0.13
24	4.92	5.08	−0.16	5.09	−0.17
25	4.22	4.29	−0.07	3.96	0.27
26	5.15	5.32	−0.17	5.02	0.13
27	4.77	4.65	0.12	4.74	0.03
28	5.70	5.59	0.11	5.31	0.39
29	4.72	4.73	−0.01	4.53	0.19
31	4.72	4.82	−0.10	4.73	−0.01
32	4.03	3.86	0.17	4.17	−0.14
33	5.40	5.57	−0.17	5.12	0.28
35	5.30	5.32	−0.02	5.42	−0.12
37	5.05	5.10	−0.05	4.80	0.25
38	4.66	4.55	0.11	4.58	0.09
39	4.00	4.41	−0.41	4.47	−0.47
41	4.00	4.06	−0.06	4.26	−0.26
42	4.00	3.98	0.02	3.97	0.04
43	4.00	4.02	−0.01	4.10	−0.10
44	4.92	4.79	0.14	5.05	−0.13
45	6.00	5.73	0.27	5.61	0.39
46	5.70	5.79	−0.09	5.93	−0.23
49	4.77	4.61	0.16	4.78	−0.01
50	4.09	4.01	0.09	3.99	0.10
51	4.00	3.99	0.01	4.17	−0.17
53	4.40	4.49	−0.09	4.30	0.10
54	4.51	4.42	0.09	4.31	0.20
55	4.00	4.16	−0.16	4.04	−0.04
56	4.74	5.04	−0.30	4.83	−0.09
57	4.21	4.48	−0.27	4.37	−0.16
59	4.00	4.02	−0.02	4.52	−0.52
60	5.30	4.93	0.38	4.95	0.35
61	4.82	4.90	−0.08	4.78	0.04
62	5.10	5.07	0.03	5.10	0.00
63	4.74	4.85	−0.11	4.83	−0.09
64	5.22	4.79	0.43	5.21	0.01
65	4.00	4.51	−0.51	4.00	0.00
67	5.22	5.20	0.02	5.44	−0.22
68	5.40	5.40	0.00	5.20	0.20
69	4.00	4.15	−0.15	4.22	−0.22
70	4.00	4.17	−0.17	4.12	−0.12
71	4.00	4.16	−0.16	4.29	−0.29
72	4.77	4.63	0.14	4.69	0.08
74	5.10	5.11	−0.01	5.01	0.09
75	4.27	4.13	0.14	4.32	−0.05
77	4.00	4.01	−0.01	4.19	−0.19
78	4.96	4.88	0.08	4.63	0.33
79	4.70	4.38	0.32	4.37	0.33
80	4.82	5.09	−0.27	4.82	0.00
81	5.10	4.89	0.22	4.80	0.30
84	5.05	5.04	0.01	5.28	−0.23
86	5.00	4.98	0.02	5.13	−0.13
88	5.82	5.66	0.16	5.63	0.19
89	4.36	4.36	0.00	4.37	−0.01
90	4.62	4.81	−0.19	4.90	−0.28
91	4.77	4.53	0.24	4.86	−0.09
93	4.55	4.35	0.20	4.42	0.13
94	4.07	4.11	−0.04	4.51	−0.44
95	6.52	6.50	0.02	6.59	−0.07
97	4.00	4.17	−0.17	4.07	−0.07
98	4.31	4.31	0.00	4.11	0.20
100	4.38	4.65	−0.27	4.46	−0.08
101	4.00	3.86	0.14	3.81	0.19
102	4.00	4.18	−0.18	3.91	0.10
103	4.25	4.24	0.01	4.25	0.00
104	4.00	4.11	−0.11	4.27	−0.27
106	4.62	4.67	−0.05	4.54	0.09
107	4.24	4.76	−0.52	4.47	−0.23
108	4.68	4.46	0.23	4.82	−0.14
110	4.38	4.26	0.12	4.41	−0.03
111	4.00	4.02	−0.02	4.06	−0.05
113	4.77	4.80	−0.03	4.60	0.17
114	4.00	3.84	0.17	3.80	0.20
115	4.00	3.78	0.22	3.91	0.09
118	4.04	4.13	−0.09	4.00	0.04
119	4.19	4.32	−0.13	4.42	−0.23
120	4.00	4.01	−0.01	4.09	−0.09
121	4.00	4.05	−0.05	4.20	−0.20
123	4.30	4.22	0.08	4.24	0.06
125	4.44	4.37	0.07	4.32	0.12
126	4.80	4.73	0.07	4.75	0.05
127	4.00	4.12	−0.12	4.16	−0.16
128	4.00	4.13	−0.13	4.26	−0.26
129	4.30	4.21	0.09	4.30	0.00
131	4.04	4.20	−0.16	3.89	0.16
132	4.00	4.02	−0.02	4.03	−0.03
133	4.41	4.47	−0.06	4.52	−0.11
134	4.00	3.98	0.02	3.74	0.26
135	4.00	3.96	0.04	3.84	0.16
136	4.00	4.15	−0.15	3.90	0.11
137	4.11	4.35	−0.24	4.34	−0.23
139	4.00	3.97	0.03	4.02	−0.02
140	4.03	4.00	0.04	4.02	0.01
141	4.15	4.12	0.03	4.28	−0.13
142	4.00	3.98	0.02	4.10	−0.10
143	4.10	4.09	0.01	4.22	−0.12
144	4.00	4.14	−0.14	4.07	−0.07
145	4.15	4.17	−0.02	4.12	0.04
146	4.30	4.24	0.06	4.30	0.00
147	4.30	4.20	0.10	4.29	0.01
148	4.52	4.52	0.00	4.62	−0.10
149	4.00	4.07	−0.07	4.21	−0.21
151	4.40	4.34	0.06	4.39	0.01
152	4.22	4.01	0.21	4.01	0.21
153	4.00	4.18	−0.18	4.05	−0.05
154	4.35	4.19	0.17	4.17	0.18
156	4.39	4.30	0.09	4.31	0.08

Table 6. Model B CoMFA and CoMSIA analyses experimental and predicted pCC₅₀ values of the test set compounds.

		CoMFA model		CoMSIA model
Compound	Exp. pCC50	Pred. pCC50	Residual	Pred. pCC50	Residual
1	4.00	4.10	−0.10	4.10	−0.10
5	4.00	3.92	0.08	3.98	0.02
19	4.00	4.24	−0.24	4.23	−0.23
21	4.89	4.97	−0.08	4.82	0.07
30	4.00	4.40	−0.40	4.33	−0.33
34	4.70	5.00	−0.30	4.76	−0.06
36	5.22	4.80	0.42	5.18	0.04
40	4.00	4.02	−0.01	4.12	−0.12
47	5.52	5.52	0.00	5.61	−0.09
48	4.77	4.51	0.26	4.77	0.00
52	4.46	4.55	−0.09	4.34	0.13
58	4.72	4.46	0.26	4.65	0.07
66	5.00	4.59	0.41	4.76	0.24
73	4.00	4.30	−0.30	4.27	−0.27
76	4.74	4.40	0.34	4.22	0.52
82	5.04	5.05	0.00	5.29	−0.25
83	4.80	4.87	−0.07	4.97	−0.17
85	4.00	4.30	−0.30	4.43	−0.43
87	4.66	5.20	−0.54	5.13	−0.47
92	4.72	5.05	−0.33	5.23	−0.51
96	4.00	4.53	−0.53	4.42	−0.42
99	4.48	4.55	−0.07	4.21	0.27
105	4.00	4.49	−0.49	4.34	−0.34
109	4.60	4.63	−0.03	4.86	−0.26
112	4.33	4.19	0.14	3.52	0.81
116	4.00	3.89	0.11	3.95	0.05
117	4.00	4.37	−0.37	4.23	−0.23
124	4.43	4.57	−0.14	4.70	−0.27
130	4.04	4.23	−0.19	4.32	−0.28
138	4.00	4.00	0.00	3.94	0.06
150	4.05	4.08	−0.03	4.08	−0.03
155	4.00	4.18	−0.18	4.14	−0.14

Figure 2. Contour map of model A CoMFA steric regions are shown around the anti-RSV agent 44 (a) and 11 (b). The compounds are displayed in ball and stick mode.

Figure 3. Contour map of model A CoMFA steric regions are shown around the anti-RSV agent 126 (a) and 148 (b). The compounds are displayed in ball and stick mode.

Figure 4. Contour maps of model A CoMFA electrostatic regions are shown around the anti-RSV agents 44 (a) and 11 (b). The compounds are displayed in ball and stick mode.

Figure 5. Contour maps of model A CoMFA electrostatic regions are shown around the anti-RSV agents 126 (a) and 148 (b). The compounds are displayed in ball and stick mode.

Figure 6. Model A CoMSIA hydrophobic favoured and disfavoured regions are shown around the anti-RSV agents 126 (a) and 148 (b). The compounds are displayed in ball and stick mode.

Figure 7. Model A CoMSIA H-bond acceptor favoured and disfavoured contour maps are displayed around benzimidazoles 126 (a) and 148 (b). The compounds are displayed in ball and stick mode.

Figure 8. Model A CoMSIA H-bond donor favoured and disfavoured contour maps are shown around the anti-RSV agents 126 (a) and 148 (b). The compounds are displayed in ball and stick mode.

Figure 9. Contour map of model B CoMFA steric regions are shown around the anti-RSV agent 95 (a) and 156 (b). The compounds are displayed in ball and stick mode.

Figure 10. Contour maps of model B CoMFA electrostatic regions are shown around the anti-RSV agents 95 (a) and 156 (b), represented in stick mode.

Figure 11. Model B CoMSIA hydrophobic favoured and disfavoured regions are shown around the anti-RSV agents 95 (a) and 156 (b), represented in stick mode.

Figure 12. Model B CoMSIA H-bond acceptor favoured and disfavoured contour maps are displayed around benzimidazoles 95 (a) and 156 (b), depicted in stick mode.

Figure 13. Model B CoMSIA H-bond donor favoured and disfavoured contour maps are shown around the anti-RSV agents 95 (a) and 156 (b), represented in stick mode.

Figure 14. Chemical structure of the anti-RSV agent BMS-433771.

Figure 15. Chemical structures and biological data about the prototypes 120, 126 and the 5-methyl newly synthesised analogues 157, 158.