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.
Our Fsp³-enriched Fragment Library comprises around 21,500 sp³-rich fragments, selected from the main General Fragment Library by applying the Fsp³ cut-off at 0.47 as well as MW ≤ 300 and ClogP ≤ 3.0.
Additionally, a Diversity Screening Set of 1,600 structurally-diverse sp3-rich fragment-like molecules 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.
Please, contact us at orders@lifechemicals.com for any additional information and price quotations.
Figure 1. Compound distribution by the key physchem parameters in the Fsp3-enriched Fragment Library.
Representative non-flat sp3-enriched fragments from the Fsp³-enriched Fragment Diversity Screening Set
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