3D Pharmacophore Models for Thromboxane A2 Receptor Antagonists
Jing Wei·Yixi Liu·Songqing Wang[(]
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, P.R. China
Supplement
Fig. S1 Structures of compounds 33~62 in the HypoGenRefine test set
Fig. S2 Structures of compounds 63~74 in the HipHop test set
Fig. S3 The best quantitative model Hypo-1. Pharmacophore features are color-code with green for hydrogen bond acceptor (HBA), cyan for hydrophobic (H), orange for aromatic ring (RA), and black for excluded volumes (EV)
Fig. S4 Plot of predicted activities against experimental values (Ki in nM) of the HypoGen training and test sets
Fig. S5 The mapping of 5 (pink) and 6 (green) with models. a: Hypo-1 model; b: Hypo-1 model without EV1 and EV2 . Color coding of pharmacophore features is as described for Fig. S3
Fig. S6 The best qualitative model Hypo-2. Color coding of pharmacophore features is as described for Fig. S3
Fig. S7 Hypo-2 model mapped with some of compound 27-purple and 68-green. Color coding of pharmacophore features is as described for Fig. S3
Fig. S8 Hypo-2 model mapped with some of compound 70 (purple) and 71 (green). Color coding of pharmacophore features is as described for Fig. S3
Fig. S9 Hypo-2 model mapped with some of compound 28 (light blue) and 72 (purple). Color coding of pharmacophore features is as described for Fig. S3
Fig. S10 Hypo-2 model mapped with some of compound 73 (green) and 74 (purple). Color coding of pharmacophore features is as described for Fig. S3
Table S1 Experimental biological data and estimated Ki of HypoGen test set molecules based on Hypo-1 model
[nM] / Est Ki
[nM] / Error / Act Ki scalea / Est Ki
scalea
42 / 11 / 1.8 / 0.75 / -2.4 / +++ / +++
43 / 11 / 2.7 / 0.79 / -3.4 / +++ / +++
44 / 11 / 3.2 / 1.7 / -1.9 / +++ / +++
45 / 11 / 3.4 / 1.2 / -2.8 / +++ / +++
46 / 11 / 3.6 / 9.9 / +2.8 / +++ / +++
36 / 11 / 3.7 / 2.4 / -1.5 / +++ / +++
47 / 11 / 9.6 / 5.9 / -1.6 / +++ / +++
39 / 12 / 14 / 7.3 / -1.9 / ++ / +++
48 / 11 / 15 / 4.8 / -3.1 / ++ / +++
40 / 12 / 18 / 23 / +1.3 / ++ / ++
50 / 13 / 20 / 3.2 / -6.3 / ++ / ++
35 / 11 / 37 / 12 / -3.1 / ++ / ++
38 / 14 / 40 / 23 / -1.7 / ++ / ++
51 / 13 / 40 / 38 / -1.1 / ++ / ++
52 / 13 / 40 / 29 / -1.4 / ++ / ++
49 / 11 / 46 / 25 / -1.8 / ++ / ++
33 / 11 / 63 / 15 / -4.2 / ++ / ++
53 / 13 / 70 / 20 / -3.5 / ++ / ++
54 / 13 / 70 / 20 / -3.5 / ++ / ++
37 / 12 / 77 / 25 / -3.1 / ++ / ++
55 / 13 / 80 / 24 / -3.3 / ++ / ++
34 / 15 / 120 / 360 / +3.0 / ++ / ++
60 / 13 / 170 / 240 / +1.4 / ++ / ++
56 / 13 / 170 / 35 / -4.9 / ++ / ++
41 / 15 / 490 / 410 / -1.2 / ++ / ++
61 / 13 / 530 / 340 / -2.2 / ++ / ++
62 / 13 / 14700 / 5000 / -2.9 / + / +
57 / 13 / 19700 / 2200 / -9.0 / + / +
58 / 13 / 27300 / 12000 / -2.3 / + / +
59 / 13 / 46200 / 28000 / -1.7 / + / +
a Activity scale: highly active (10 nM, +++), moderately active (10~1000 nM, ++), or inactive (>1000 nM, +)
Table S2 Best fit values (Fit) of the TXARs HipHop training and test set mapped on the best HipHop model Hypo-2
No. / Fita / Mapped featureb / No. / Fita / Mapped featureb
HBA1 / HBA2 / H1 / H2 / HBA1 / HBA2 / H1 / H2
36 / 3.92 / + / + / + / + / 19 / 3.69 / + / + / + / +
21 / 3.02 / + / + / + / + / 43 / 3.08 / + / + / + / +
26 / 3.73 / + / + / + / + / 63 / 3.65 / + / + / + / +
27 / 3.96 / + / + / + / + / 69 / 3.34 / + / + / + / +
29 / 3.78 / + / + / + / + / 68 / 3.96 / + / + / + / +
30 / 3.88 / + / + / + / + / 65 / 3.87 / + / + / + / +
31 / 3.05 / + / + / + / + / 64 / 3.19 / + / + / + / +
32 / 3.65 / + / + / + / + / 66 / 3.33 / + / + / + / +
28 / 3.05 / + / + / + / + / 67 / 3.53 / + / + / + / +
70 / 3.08 / + / + / + / +
71 / 3.27 / + / + / + / +
72 / 3.18 / + / + / + / +
73 / 3.28 / + / + / + / +
74 / 3.54 / + / + / + / +
a The number represents the best fit of each molecule to the hypothesis. The higher the best fit value is, the better a molecule maps the features of a hypothesis. The best fit value of 4.00 means a perfect mapping of the molecule to the hypothesis
b The “+” sign means the chemical feature of a compound maps the corresponding feature of the hypothesis
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