Table 1. Predicted binding affinities (or docking scores) and selected medicinal–chemical properties for the parent compounds and their analogs. Top part of the Table is for Ketoprofen and its analogs 1–7; bottom part is for Donepezil and its analogs 11, 14, 16. The first two columns specify, respectively, K_i values predicted by AutoDock Vina and by AutoDock 4. The third column has the docking score from Dock 6. The values shown are averages over all stereoisomers (files with the docked individual stereoisomers are deposited at https://zenodo.org/records/14571461). The remaining four columns give the Allchemy-predicted values of log P calculated by group contribution method⁸⁰ as well as predictions of Allchemy's machine-learning models for hERG cardiotoxicity (on a 0–1 scale), degree of human plasma protein binding, hPPB, related to drug absorption and efficacy (0–100%), and degree of blood–brain barrier, BBB, penetration (0–1). Although none of the models used Ketoprofen or Donepezil molecules for training/testing, the key predictions match experimental data. For instance, the hERG model correctly predicts Donepezil to be cardiotoxic (values close to 1), which is in line with experimental studies evidencing that Donepezil binds to hERG⁸¹ with IC₅₀ = 1.3 μm and can cause QTc prolongation.⁸² By contrast, the model predicts low values of hERG inhibition for Ketoprofen (and its analogs), which agrees with experiments confirming its low cardiotoxicity.⁸³ In turn, the hPPB model predicts high, >90% bound fractions for both Ketoprofen and Donepezil and their analogs – while lower hPPB values are, in principle, desired in drug design, these predicted values agree with experimental measurements for Ketoprofen (99%⁸⁴) and Donepezil (95.6%⁸⁵). In turn, the blood–brain barrier, BBB, penetration model predicts high values for Donepezil, which is expected for a CNS drug and experimentally confirmed.⁸⁶ Ketoprofen also crosses the BBB⁸⁷ but we note that some of the analogs, more polar ones, are predicted to have significantly lower values.

Compound	K i AutoDock Vina (μM)	K i AutoDock (μM)	Dock 6 (score)	log P	hERG (0–1)	hPPB (0–100%)	BBB (0–1)
Ketoprofen	0.613	0.284	−33.03	3.106	0.04	98.40 ± 1.20	0.91
1	0.413	0.202	−34.85	3.015	0.03	98.50 ± 1.00	0.84
2	0.814	0.268	−34.62	4.052	0.1	98.80 ± 1.30	0.64
3	0.579	0.161	−33.40	3.065	0.01	97.00 ± 1.30	0.42
4	1.138	0.224	−34.82	3.662	0.09	98.60 ± 1.20	0.69
5	0.538	0.348	−36.74	2.857	0.01	94.30 ± 1.20	0.46
6	0.451	0.154	−33.19	2.561	0	96.50 ± 2.70	0.37
7	0.534	0.264	−39.15	2.728	0	95.80 ± 3.60	0.29
Donepezil	0.046	0.037	−43.78	4.361	0.96	91.70 ± 1.30	0.92
11	0.086	0.061	−41.76	4.357	0.98	90.80 ± 1.10	0.9
12	0.064	0.069	−42.54	4.671	0.95	95.80 ± 1.20	0.75
13	0.204	0.097	−43.06	3.722	0.92	88.90 ± 1.10	0.66
14	0.037	0.053	−42.55	3.930	0.92	93.90 ± 4.70	0.77
16	0.027	0.011	−46.98	3.833	0.97	89.60 ± 1.20	0.75