CP-MLR/PLS directed QSAR study on the glutaminyl cyclase inhibitory activity of imidazoles: rationales to advance the understanding of activity profile

Figures & data

Table 1.  Observed and predicted glutaminyl cyclase (QC) inhibitory activity of imidazoles.

Com.^a	R1	pKi			Com.^a	R1	pKi
		Obd.	Eq. 1	PLS			Obd.	Eq. 1	PLS
01^b		5.82	5.30	4.79	24^b		6.64	6.76	6.68
02		5.86	5.27	5.30	25		7.75	8.02	7.61
03^b		5.99	5.92	5.80	26		7.77	7.21	7.54
04		5.96	6.05	5.96	27^b		7.41	7.59	7.65
05		5.17	5.86	5.62	28		7.70	7.86	7.37
06		6.08	5.97	5.90	29		7.08	7.54	7.56
07		6.16	5.63	5.54	30		7.22	7.05	7.57
08		5.87	6.27	6.18	31		7.39	6.71	7.10
09		6.21	5.83	5.55	32		5.78	5.88	6.09
10		4.69	5.82	5.38	33		5.89	5.94	6.53
11^b		6.30	6.15	6.53	34^b		8.20	8.00	7.97
12		5.93	6.23	6.25	35		8.59	8.43	8.53
13^b		6.24	6.27	6.40	36^b		7.09	7.01	7.13
14		6.27	6.04	6.24	37		6.60	7.20	7.13
15^b		6.28	6.23	6.19	38		7.19	7.39	7.03
16		5.99	5.91	6.00	39		6.89	6.83	6.58
17^b		6.22	6.21	6.51	40		7.22	7.08	6.94
18		6.27	5.96	6.06	41		7.36	6.98	7.37
19		6.52	6.97	6.40	42		7.29	7.10	7.27
20		6.44	6.80	6.58	43		7.47	6.91	7.08
21^b		6.47	6.30	6.53	44		7.38	7.03	7.04
22		6.21	6.03	6.07	45^b		7.17	6.86	6.93
23		6.05	6.74	6.83

^aIn compound 1–23, R₂ and R₃=H; comp. 24, 30–33 R₂=H and R₃=CH₃; comp. 25–29, 34–45, R₂=CH₃ and R₃=H.

^bTest set compounds.

Figure 1.  Plots of training (*) and test (•) sets predicted activities versus observed activity corresponding to equation 1 and PLS model. Number of compounds in training set is 33 and test set is 12.

Table 2.  Pearson correlation coefficient values of parameters of equation 1–3 with QC inhibitory activity of imidazoles.

	MATS1p	GATS6p	GATS7v	H-048	MR	MlogP
MATS1p	1.000
GATS6p	0.230	1.000
GATS7v	0.156	−0.231	1.000
H-048	−0.088	−0.152	0.100	1.000
MR	0.630	0.443	−0.250	−0.268	1.000
MlogP	0.318	−0.191	0.055	−0.527	0.304	1.000
pKi	0.431	0.601	−0.385	−0.634	0.673	0.301

Figure 2.  Plot of fraction contribution of MLR-like PLS coefficients (normalized) of the 59 descriptors to the activity. The horizontal axis refers to descriptors’ serial numbers. The 13 most significant descriptors are identified by gray shaded lines.