Fragment-based Cocktails

The efficiency of fragment screening can be increased substantially by pooling or cocktailing the compounds in the library. Identification of the bound fragment at the end of the X-Ray, NMR or ligand-observed LC/MS experiments then becomes a case of determining the best fragment-fit. Life Chemicals Fragment Cocktails Libraries are performed in sets of fragments with the selected components chosen to be most chemically and shape diverse within a particular cocktail.

Fluorine Fragments Cocktails

Life Chemicals has designed unique Library of Fluorine Fragment Cocktails employing Rule of Three criteria and MedChem structure filters including PAINS. The choice of fluorinated motifs present in the library is fundamental in order to ensure a large coverage of chemical space and local environment of fluorine. The Library is pooled in a sets of 10 fragments with most different 19F chemical shifts to facilitate interpretation of the screening results.

Carefully collected 73 cocktails comprise drug-like fluorine fragments characterized with following parameters:
1H and 19F NMR spectra
● Purity 95%+
● ensured DMSO solubility at 200 mM

PhysChem Parameters of the Library

● 130 < MW < 300
● -1.7 < ClogP < 3.0
● H-bond Donors ≤ 3
● H-bond Acceptors ≤ 4
● TPSA ≤ 110 Å2

Structure Filters Applied

● no reactive functional groups
● Lilly MedChem rules
● PAINS (families A, B, C)
● Ring count 1 - 3

Fluorine Fragment Library graph


Chemical space covered by Life Chemicals' Fluorinated Fragments (colored in blue) is similar to all commercially available F-fragments (in red).

Shape-wise diverse Fragment Cocktails

Cocktailing was conducted in sets of five with the selected components chosen to be as chemically and shape diverse as possible within a particular cocktail.