A Quantitative Structure-Activity Relationship and Molecular Modeling Study on a Series of Biaryl Imidazole Derivatives Acting as H⁺/K⁺-ATPase Inhibitors

Table 1

A series of H⁺/K⁺-ATPase inhibitors and their activity.

(a)  

S. no.	R	GTCI	TPSA	I1	I2		log (1/IC50)
						Obsd^a	Calcd, (1)	Pred (LOO)
1	Et	0.50	72.42	1.00	0.00	7.00	7.04	7.06
2	Me	0.52	72.42	1.00	0.00	7.10	7.11	7.10

(b)  

S. no.	X	Ar^1	GTCI	TPSA	I1	I2		log (1/IC50)
							Obsd^a	Calcd, (1)	Pred (LOO)
3	—	Ph	0.40	28.68	0.00	0.00	4.70	4.68	4.67
4	—	2-Me-Ph	0.45	28.68	0.00	0.00	5.10	4.83	4.80
5	—	2,6-diMe-Ph	0.48	28.68	0.00	0.00	5.20	4.95	4.91
6	—	2,6-diEt-Ph	0.44	28.68	0.00	0.00	5.10	4.82	4.78
7 ^b	—	3-Me-triophene-4-yl	0.45	28.68	0.00	0.00	4.80	4.85	—
8	NH	2,6-diMe-Ph	0.48	40.71	0.00	1.00	4.90	4.53	4.4
9	(trans) CH=CH	Ph	0.38	28.68	0.00	1.00	4.40	4.03	3.87
10 ^b	CH2CH2	Ph	0.38	28.68	0.00	1.00	4.30	4.03	—
11	NHC0H2	2,6-diMe-Ph	0.47	40.71	0.00	1.00	4.30	4.57	4.55^b
12	CONH	Ph	0.42	57.78	0.00	1.00	4.00	4.58	4.72
13 ^b	Ortho	Ph	0.38	28.68	0.00	1.00	4.20	4.00	4.17
14	Para	2,6-diMe-Ph	0.50	28.68	0.00	1.00	4.40	4.40	4.43

(c)  

S. no.	X	Y	R^1	R^2	R^3	GTCI	TPSA	I1	I2		log (1/IC50)
										Obsd^a	Calcd, (1)	Pred (LOO)
15 ^b	N	C	H	H	H	0.36	28.68	0.00	0.00	4.50	4.53	—
16	N	C	H	Et	Et	0.45	26.68	0.00	0.00	4.80	4.80	4.80
17	N	C	H	Ph	—	0.36	28.68	0.00	0.00	4.40	4.52	5.32
18^c	N	C	Me	H	H	0.41	17.82	0.00	0.00	5.20	4.54	—
19 ^b	N	C	Me	Me	Me	0.49	17.82	0.00	0.00	4.60	4.83	—
20	N	C	N-Pr	H	H	0.39	17.82	0.00	0.00	4.30	4.46	4.48
21 ^b	CH	N	—	Me	Me	0.48	17.82	0.00	0.00	4.80	4.80	—
22	CH	N	n-Pr	H	—	0.41	17.82	0.00	0.00	4.40	4.54	4.55
23	—	—	—	—	—	0.42	38.91	0.00	0.00	4.50	4.86	4.88
24	—	—	—	—	—	0.43	6.48	0.00	0.00	4.40	4.46	4.47
25 ^b	—	—	—	—	—	0.42	12.03	0.00	0.00	4.30	4.50	—

(d)  

S. no.	R	GTCI	TPSA	I1	I2		log (1/IC50)
						Obsd^a	Calcd, (1)	Pred (LOO)
26^c	6-OMe	0.50	37.91	0.00	0.00	6.10	5.15	—
27	4-OMe	0.50	37.91	0.00	0.00	4.90	5.14	5.12
28	4-Me	0.51	26.68	0.00	0.00	4.90	5.04	5.04
29^c	5,6-DiMeO	0.50	69.14	0.00	0.00	4.60	5.59	—
30	6-OH	0.52	48.91	0.00	0.00	5.70	5.37	5.28
31 ^b	6-OEt	0.48	37.91	0.00	0.00	5.60	5.09	—
32	6-OBn	0.42	37.91	0.00	0.00	5.30	4.87	4.81
33	6-OBn	0.52	37.91	0.00	0.00	5.00	5.20	5.20
34	6OCH2CO2Me	0.49	64.21	0.00	0.00	5.90	5.48	5.35
35	6OCH2CONH2	0.49	90.82	0.00	0.00	5.70	5.85	5.88
36 ^b	—	0.46	37.91	0.00	0.00	5.50	5.01	—
37	—	0.46	41.82	0.00	0.00	5.40	5.07	5.02
38	6-OMe-pyrid-5-yl	0.42	50.80	0.00	0.00	4.80	5.05	5.04
39 ^b	—	0.48	27.05	0.00	0.00	4.90	4.91	—
40	2,5-Furanyl	0.50	41.82	0.00	0.00	4.90	5.20	5.23
41^c	2,5-Thienyl	0.50	28.68	0.00	0.00	4.10	5.02	—
42	2,4-Thienyl	0.50	28.68	0.00	0.00	4.50	5.02	5.05

^aTaken from [1]. ^bTaken for test set. ^cNot used in the derivation of (1) as they were outlier.