Bromine Fragment Library

Crystallographic fragment-based drug discovery (FBDD) has been gaining high importance in modern pharmaceutical technology. Fragments, however, are poor binders, with their partial occupancy resulting in weak, difficult-to-fit electron density. The use of brominated fragments and X-ray crystallography can address this challenge, as bromine can be located uniquely via anomalous scattering, and thus, provide further insight into the nature of the target surface pocket [1].

The Life Chemicals Bromine Fragment Library consists of about 1,700 drug-like compounds with MW ≤ 350 and ClogP ≤ 3.5. All the fragments contain only one Br-atom. Other important parameters (such as HBA, HBD, Fsp3, RotB, TPSA) are included in the data file and can be used for selection with multiple restrictions. While this library is available for regular cherry-picking, a specially tailored diversity set can be arranged per the customer’s needs.

An Advanced Subset of almost 1,100 brominated fragments was composed based on the physicochemical parameters reported in the table. All reactive compounds and undesired chemotypes were removed; PAINS filters are applied.

Parameter

Range

MW

< 350

ClogP

< 3.5

Fsp³

> 0.4

Number of rings

1 - 3

Rotatable bonds

≤ 4

H-donors

0 - 3

H-acceptors

0 - 4

 Representative bromine-containing fragments

References

  1. Tiefenbrunn T. et al. Chem Biol Drug Des. 2014, 83, 141–148
  2. Peng H et al. Environ Sci Technol. 2016 Dec 6;50(23):12669-12677.