Fsp3-enriched Compounds

Fsp3-enriched Library was designed due to increased importance of molecular complexity and the presence of chiral centers in organic compounds, that rise their potential to be suitable drug candidates and efficiently fills uncovered biologically relevant chemical space.

Life Chemicals Fsp3-enriched Library contains 27,000 drug-like stock compounds.

The Library was designed as a result of increased understanding of importance of molecular complexity and the presence of chiral centers in organic compounds, which increases their potential to be suitable drug candidates.

In a recent study it has been shown that the mean Fsp3 (Fsp3 = number of sp3 hybridized carbons / total carbon count) increases from 0.36 for 2.2 million molecules in discovery to 0.47 for 1,179 approved drugs. Combined with low molecular weight and cLogP values the higher Fsp3 count leads to higher bioavailability and specificity of compounds thus making them attractive for drug discovery process. The PAINS and in-house developed toxicophore & undesired functionalities filtering were also applied. In order to create Fsp3-enriched Library we have selected molecules with the following physicochemical characteristics derived as a result of combined analysis of publications on this subject1-5:

Fsp3-enriched Library Range Average Value
Molecular Weight 150 - 450 Da 356,21 Da
Fsp3 0,45 0,61
cLogP < 4 1,58
TPSA <140 Å2 82,52 Å2
H-acceptors ≤ 8 3,5
H-donors ≤ 4 1,5
Rotatable Bonds ≤ 8 4,82
Number of Carbonaromatics ≤ 1 0,69

 


References
1. AstraZeneca J. Med. Chem. 2010, 53, 7709-7714
2. GSK, Drug Discovery Today, V.16, Numbers 3/4, Feb. 2011
3. Broad Institute of Harvard and MIT, PNAS November 2, 2010, vol. 107, no. 44, 18787-18792
4. The Walter and Eliza Hall Institute of Medical Research, J. Med. Chem. 2010, 53, 2719-2740
5. Wyeth, J. Med. Chem. 2009, 52, 6752-6756