Fragment-based drug discovery (FBDD) projects performed with 19F NMR-assisted screening are becoming an essential and widespread method in drug discovery. Fluorine yields a strong, sharp and distinct signal in NMR spectra. It has a wide chemical shift range and is highly sensitive to the immediate molecular environment. These factors allow an efficient application of this method in laboratories with limited NMR setup and screening several compounds together without them interfering with each other.
Additionally, the efficacy 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 NMR experiments then becomes a case of determining the best fragment-fit.
Life Chemicals has designed its unique Fluorine Fragment Cocktail Library employing several physicochemical parameters and medicinal chemistry structure filters. The choice of fluorinated fragments present in the library is fundamental to ensure broad coverage of chemical space and the local environment of fluorine.
The Library is pooled in sets of 10 fragment-like screening compounds with the most different 19F chemical shifts in order to facilitate screening results interpretation. Carefully collected 140 Fluorine Fragment Cocktails comprises 1,400 in-stock drug-like fluorine-containing fragments from our proprietary Fluorine Fragment Library that satisfy the following parameters:
- Single-type fluorine group
- Only 1 peak in the 19F NMR spectrum in the majority of cases
- Ro3 compliant
- DMSO soluble at 200 mM
- PBS soluble at ≥ 0.1mM
- Purity > 90 %
Overall physicochemical parameters of the Library:
- 120 < MW < 300
- -2.6 < ClogP < 4.2
- H-bond Donors ≤ 4
- H-bond Acceptors ≤ 6
- Rotatable bonds ≤ 10
- TPSA ≤ 130 Å2
An example of the 19F NMR spectrum of a sample fluorine fragment pool with signals attributed to each compound is depicted in Figure 1.
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Figure 1. 19F NMR spectrum of a sample pool of 10 fluorine-containing fragments selected for Fluorine Cocktails. All peaks are assigned to the corresponding compounds
- Nagatoishi S, Yamaguchi S et al. Bioorg Med Chem. 2018 May 1; 26(8):1929-1938.
- Norton, R.; Leung, E.; Chandrashekaran, I.; MacRaild, C. Molecules 2016, 21 (7), 860.
- Nosik, P. S., Gerasov, A. O. et al. Adv. Synth. Catal. 359 (2017), 3126-3136
- Gerasov, A., Dolgonos, G. A. et al. Synthesis (Stuttg). Published online: 2020 Jan.