The mean saturation degree Fsp3 (calculated as number of sp3 hybridized carbons / total carbon count) was shown to increase from 0.36 for 2.2 million molecules at the development stage to 0.47 for 1,179 of approved drugs. A higher Fsp3 count together with low molecular weight and ClogP values, leads to higher bioavailability and specificity of compounds, thus making them attractive for drug discovery process.
In response to these new trends in drug discovery, involving comprehensive structural analysis of approved drugs and determination of relationships between molecular complexity and pharmacological promiscuity of drug-like compounds [1–5], Life Chemicals has extrapolated the results of described investigations to its Fragment Library design.
Applying the Fsp³ cut-off at 0.45 to the Life Chemicals General Fragment Library resulted in our Fsp³-enriched Fragment Library of around 19,900 sp³-rich screening compounds. Physicochemical parameters are summarized in the table below:
| Parameter | MW | ClogP | Fsp3 | TPSA | RotB | HBD | HBA | Benzene rings |
| Selection range | ≤ 300 | < 3 | ≥ 0.45 | < 90 Å2 | ≤ 3 | ≤ 3 | ≤ 3 | ≤ 1 |
| Average value | 247.5 | 1.1 | 0.6 | 59.2 | 3.4 | 1.4 | 2.9 | ≤ 1 |
Additionally, a Diversity Screening Set of 1,600 structurally-diverse sp3-rich fragments was prepared to provide the most-promising drug-like screening compounds for fragment-based lead discovery in a convenient manner. These fragment-like molecules possess a wide range of chemical structure dissimilarity and are compliant with in-house MedChem and PAINS structural filters [6-7].
The compound selection can be customized based on your requirements, cherry picking is available.
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Representative compounds from Fsp³-enriched Fragment Library
References
- Yang Y. et al. J. Med. Chem. 2010, 53, 7709–7714.
- Ritchie T. J. et al. Drug Discov. Today 2011, 16 (3-4), 164-171.
- Clemons P. A. et al. PNAS 2010, 107 (44), 18787–18792.
- Baell J. B.; Holloway G. A. J. Med. Chem. 2010, 53, 2719–2740.
- Lovering F.; Bikker J.; Humblet C. J. Med. Chem. 2009, 52, 6752–6756.
- Troelsen NS et al. The 3F Library: Fluorinated Fsp3 -Rich Fragments for Expeditious 19 F NMR Based Screening. Angew Chem Int Ed Engl. 2019