Table 1. Overview of the In Silico Approach Taken by Each Partner Company, along with the Number of Compounds Furnished from Each Partner.
| number
of compounds booster round A/B (actives)b |
|||
|---|---|---|---|
| company and computational approacha | total | 2-arylpyrimidinec | 2-arylquinazolined |
| A—the top scoring 150 compounds were selected by Tanimoto similarity calculation using the FCFP4 fingerprint, followed by refinement to 96 compounds based on maximized diversity | 192 | 22/11 (9) | 2/33 (7) |
| B—similarity search using Daylight59 and Chemaxon60 fingerprints and ROCS61 TanimotoCombo scoring | 119 | 27/62 (8) | 1/5 (5) |
| C—ECFP4 similarity (Tanimoto cut-off 0.6) and in-house fingerprint search (Tanimoto cut-off 0.7). Subsequent in-house “quality”, commercial availability, and IP filters | 176 | 83/0 (14) | 3/81 (25) |
| D—series of similarity and substructure-based queries prioritized with Tanimoto similarity calculated by ECFP4 | 182 | 53/0 (24) | 30/3 (24) |
| E—ECFP4 similarity (initial Tanimoto cut-off 0.7 descending incrementally until sufficient compounds had been identified) | 126 | 0/3 (1) | 0/58 (17) |
| all companies | 795 | 185/76 (56) | 36/180 (78) |
a
Further information is found in Supporting Information 1.
b
Actives defined as compounds with SI > 5 against one or both parasites.
c
Compounds with a 2-arylpyrimidine core.
d
Compounds with a 2-arylquinazoline core.