Chemical Feature-Based Molecular Modeling of Urotensin-II Receptor Antagonists: Generation of Predictive Pharmacophore Model for Early Drug Discovery

Table 5

Actual and predicted activities of internal and external test sets based on the best pharmacophore hypothesis Hypo 1.

Compound	Actual activity IC50; (nM)	Estimated activity IC50; (nM)	Error factor	Actual activity scale^a	Estimated activity scale^a
(R)-4	84	394.107	4.7	++	++
(S)-4	490	394.107	1.2	++	++
5i	200	293.232	1.5	++	++
(R,S)-5j	69	354.464	5.1	++	++
6b	16	17.431	1.1	++	++
6e	20	110.752	5.5	++	++
6h*	11	1057.79	96.2	++	+
7b	3	5.506	1.8	+++	+++
7i	13	2.797	4.6	++	+++
External test set
3a	7100	6835.94	1.1	+	+
3b	24000	6404.1	3.7	+	+
3c	43000	6560.66	6.5	+	+
3d	12000	6460.16	1.8	+	+
3e	9100	6349.46	1.4	+	+
12a	2500	6454.92	2.6	+	+
12b	600	835.427	1.4	++	++
12c	400	688.096	1.7	++	++
12d	520	508.003	1	++	++
12e	330	709.005	2.1	++	++
12f	210	6651.93	31.7	++	+
12g	53	86.082	1.6	++	++
12h	100	820.03	8.2	++	++
12i	10	288.67	28.9	++	++
12j	1900	671.84	2.8	+	++

∗Outlier from the test set compounds.
^aActivity scale: highly active (<10 nM, +++), moderately active (10–1000 nM, ++), and inactive (>1000 nM, +).