A Quantitative Structure-Activity Relationship and Molecular Modeling Study on a Series of Heteroaryl- and Heterocyclyl-Substituted Imidazo[1,2-a]Pyridine Derivatives Acting as Acid Pump Antagonists

Table 3

Docking results of predicted compounds with reference to the active drugs available in the market (last four in the table) to treat the hyperacidity and GERD. Energy values are in kJ/mol.

Pred compd (Table 2)	Total inter. energy	H-bond energy	No. of H-bonds	H-bonds ligand-protein	H-bond; length (Å)	Mole; Dock score	Inter. E of pose
1	−175.83	−0.91	1	O(35)-Glu(97)	3.42	−176.36	−0.53
2	−178.33	−10.33	8	O(35)-Thr(350); O(35)-Gly(156); O(35)-Thr(152); N(9)-Thr(350); N(6)-Thr(350); O(33)-Gln(159); O(33)-Leu(370); O(33)-Glu(160)	3.39; 2.89; 2.85; 2.77; 3.32; 3.60; 2.91; 3.36	−197.72	−19.39
3	−179.52	−10.06	5	N(6)-Thr(350); N(9)-Thr(350); O(34)-Thr(350); O(34)-Thr(152); O(32)-Leu(370)	3.26; 2.67; 3.42; 2.17; 3.08	−180.64	−1.12
4	−148.24	−14.38	6	O(36)-Asn(369); O(35)-Gln(159); O(34)-Thr(350); O(34)-Thr(352); N(9)-Thr(350); N(6)-Thr(350)	2.68; 3.35; 3.38; 2.66; 2.72; 3.23	−168.07	−19.83
5	−191.53	−11.70	3	O(32)-Gly(107); O(33)-Gly(107); O(35)-Leu(346)	2.86; 2.93; 2.49	−191.78	−0.25
6	−154.31	−6.58	2	O(32)-Leu(346); O(32)-Thr(350)	2.51; 3.26	−177.77	−23.46
7	−176.30	−2.04	3	O(34)-Thr(350); O(33)-Thr(350); O(33)-Leu(346)	3.23; 3.26; 2.95	−190.78	−14.48
8	−172.98	−4.38	6	O(34)-Thr(350); O(32)-Gln(159); O(33)-Gly(156); O(33)-Glu(160); O(32)-Leu(370); N(6)-Gln(110)	2.75; 2.72; 2.99; 3.22; 2.95; 3.56	−183.57	−10.59
9	−152.69	−9.56	4	O(28)-Asn(369); O(30)-Glu(371); O(30)-Leu(370); O(31)-Glu(160)	3.19; 3.15; 2.60; 3.12	−170.18	−17.48
10	−146.03	−8.27	8	N(6)-Tyr(157); N(9)-Gly(153); O(31)-Gln(104); O(34)-Glu(160); O(34)-Leu(370); O(33)-Glu(160); O(33)-Asn(369); O(32)-Asn(369)	3.53; 2.71; 2.77; 2.94; 3.33; 3.05; 2.61; 3.03	−150.52	−4.50
11	−165.10	−15.21	0	—	—	−179.73	−14.63
12	−147.86	0	6	O(33)-Gln(104); O(33)-Lys(100); O(32)-Gly(153); O(27)-Glu(153); O(27)-Thr(152); O(27)-Gly(156)	3.13; 3.14; 2.67; 2.90; 3.27; 3.00	−173.20	−25.33
13	−165.88	−11.84	6	N(9)-Thr(150); N(6)-Thr(150); O(32)-Gln(104); O(29)-Gln(104); O(30)-Asn(369); O(31)-Gln(160)	2.49; 3.10; 2.92; 3.09; 2.84; 2.79	−167.27	−1.38
14	−149.50	−13.62	8	N(9)-Gly(153); O(30)-Gln(104); O(30)-Gln(104); O(31)-Leu(370); O(28)-Glu(160); O(31)-Glu(160); O(28)-Lys(368); O(29)-Asn(369)	2.60; 2.65; 3.21; 3.11; 2.68; 3.32; 3.26; 2.66	−170.60	−21.10
15	−161.87	−14.80	6	O(34)-Gln(104); O(33)-Glu(160); O(32)-Gly(156); O(32)-Thr(152); N(6)-Thr(350); N(9)-Thr(350)	2.96; 3.12; 2.90; 2.66; 3.43; 2.73	−168.46	−6.58
16	−177.11	−11.22	4	O(31)-Gln(104); O(30)-Thr(152); O(32)-Leu(370); O(32)-Glu(160)	2.87; 3.08; 3.19; 3.14	−179.76	−2.65
17	−150.98	−9.31	5	O(32)-Leu(370); O(34)-Thr(350); N(6)-Thr (350); N(9)-Thr(350); O(35)-Thr(152)	3.08; 3.42; 3.26; 2.67; 2.71	−159.32	−8.34
Rabeprazole	−144.85	−5.00	2	O(11)-Thr(350); N(13)-Thr(350)	2.63; 3.01	−131.76	13.09
Lansoprazole	−121.59	−0.10	2	O(19)-Gly(156); N(8)-Gln(104)	3.48; 3.59	−115.07	6.521
Omeprazole	−117.83	−2.42	2	O(24)-Arg(103); O(24)-Arg(103)	2.75; 3.34	−111.99	5.84
Pantoprazole	−120.43	−3.78	3	O(21)-Thr(350); N(6)-Gln(104); O(11)-Gln(110)	3.22; 3.10; 2.99	−115.41	5.02