Biochemistry Research International

Research Article

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 1

Heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]pyridine derivatives and their physicochemical parameters and H⁺/K⁺-ATPase inhibition activity.

(a)




Compd	R⁶	π _o	GTCI			Log(1/IC₅₀)
Compd	R⁶	π _o	GTCI			Obsd^a	Calcd, (1)	Pred (LOO)

1		0.56	0.48	1.00	1.00	6.5	7.17	7.27
2^c		0.56	0.49	1.00	1.00	8.4	6.97	—
3		0.56	0.45	1.00	1.00	8.3	7.50	7.43
4 ^b		0.56	0.44	1.00	1.00	8.1	7.74	—
5		0.56	0.45	1.00	1.00	7.9	7.50	7.47
6		0.56	0.43	1.00	1.00	7.4	7.88	7.99
7		0.56	0.44	1.00	1.00	7.6	7.74	7.76
8^c		0.56	0.44	1.00	1.00	6.5	7.74	—
9		0.56	0.46	1.00	1.00	6.9	7.36	7.42
10		0.56	0.45	1.00	1.00	7.6	7.52	7.51
11		0.56	0.47	1.00	1.00	7.5	7.31	7.30
12		0.56	0.49	1.00	1.00	7.1	6.95	6.90
13		0.56	0.45	1.00	1.00	7.8	7.50	7.48
14 ^b		0.56	0.45	1.00	1.00	7.0	7.50	—
15^c		0.56	0.45	1.00	1.00	6.7	6.32	—

Taken from [4]. ^bUsed for test set. ^cNot included in the derivation of (1).

(b)




Compd	R⁶	π _o	GTCI			Log(1/IC₅₀)
Compd	R⁶	π _o	GTCI			Obsd^a	Calcd, (1)	Pred (LOO)

16		1.02	0.50	0.00	1.00	7.0	6.58	7.01
17 ^b	H	1.02	0.45	0.00	1.00	8.2	7.25	—
18		1.02	0.45	0.00	1.00	7.0	7.23	7.34

Taken from [4]. ^bUsed for test set.

(c)




Compd	R⁶	π _o	GTCI			Log(1/IC₅₀)
Compd	R⁶	π _o	GTCI			Obsd^a	Calcd, (1)	Pred (LOO)

Obsd^a	Calcd, (1)	Pred (LOO)

19	CH₃	CH₃	O	0.56	0.45	1.00	1.00	7.4	7.50	7.51
20^c	CH₃	CH₃	CH₂	0.56	0.45	1.00	1.00	5.9	7.50	—
21	CH₃	H	NH	1.02	0.47	0.00	0.00	5.7	5.64	5.58
22 ^b	CH₂OH	CH₃	NH	0.56	0.45	1.00	0.00	5.4	6.30	—
23	CH₃	H	NH	0.56	0.44	1.00	0.00	6.4	6.39	6.38
24 ^b	CH₃	CH₂OH	NH	0.56	0.44	1.00	0.00	6.9	6.32	—
25	CH₃	Cl	NH	0.56	0.45	1.00	0.00	6.1	6.18	6.22

Taken from [4]. ^bUsed for test set. ^cNot included in the derivation of (1).

(d)




Compd	R⁶	π _o	GTCI			Log(1/IC₅₀)
Compd	R⁶	π _o	GTCI			Obsd^a	Calcd, (1)	Pred (LOO)

26 ^b	2-Pyridone	2-CH₃	0.56	0.43	0.00	1.00	7.2	6.55	—
27	1,2,4-Triazole	2-CH₃	0.56	0.41	0.00	1.00	6.3	6.85	7.00
28^c	2-Pyridone	2-Cl-4-F	0.71	0.47	0.00	1.00	7.0	6.37	—
29	1,2,4-Triazole	2-Cl-4-F	0.71	0.45	0.00	1.00	6.3	6.54	6.57
30	2-Pyridone	H	0.00	0.40	0.00	1.00	5.8	5.78	5.78
31	2-Pyridone	2-MeO	0.02	0.42	0.00	1.00	5.3	5.43	5.47
32	2-Pyridone	3-Me	0.00	0.44	0.00	1.00	4.7	5.18	5.46
33	2-Pyridone	—	0.00	0.39	0.00	1.00	6.2	5.86	5.78
34	1,2,4-Triazole	—	0.00	0.37	0.00	1.00	6.6	6.20	6.01

Taken from [4]. ^bUsed for test set. ^cNot included in the derivation of (1).