Scientific Papers

Crystal structures of tolfenamic acid polymorphic forms I and II with precise hydrogen-atom positions for nuclear magnetic resonance studies

Acta Cryst. E76, 1421–1426 (2020)

C4X Discovery has developed pioneering methods for routinely determining single-crystal structures on sub-milligram quantities of material, allowing us to measure and use this complementary conformational data very early in our programmes. In this report, we grow large crystals of two polymorphs of tolfenamic acid and solve their structures to high enough resolution that the hydrogen positions can be precisely determined. We use such data to refine our solution free ligand dynamic structures determined by NMR.

Pushing the limits of molecular crystal structure determination from powder diffraction data in high-throughput chemical environments

J. Pharm. Sci. 107 (8), 2042 - 2047 (2018)

We demonstrate that structure determination by powder diffraction (SDPD) can be performed much more readily than is commonly believed, providing a new stream of conformational data for our chemistry design team.

Accurate measurement of long range proton–carbon scalar coupling constants

Analyst 142, 621 - 633 (2017)

We report on the accuracy, ease of use and time efficiency of multi-dimensional methods for measuring these valuable conformational restraints.

Measurement, Interpretation and Use of Free Ligand Solution Conformations in Drug Discovery

Prog Med Chem 55, 45-147 (2016)

Our team of conformational experts describe our new paradigm for drug conformational analysis, understanding, control and design.

GPR103 Antagonists Demonstrating Anorexigenic Activity in Vivo: Design and Development of Pyrrolo[2,3-c]pyridines That Mimic the C-Terminal Arg-Phe Motif of QRFP26

J Med Chem. 57, 5935-48 (2014)

Using the Conformetrix technology, we show how a series of drug molecules is likely to be mimicking the shape of a native peptide ligand. This work illustrates how scaffold-hopping from peptides to drugs can be readily achieved.

The Conformational Musings of a Medicinal Chemist

Drug Discov Today 19 (3), 320–5 (2014)

Dr. Harry Finch (C4X NED) discusses the impact that solution conformational preference data is likely to have on drug discovery programmes.

Quantification of free ligand conformational preferences by NMR and their relationship to the bioactive conformation

Bioorg Med Chem 21(17), 4976-87 (2013)

Here we detail how we measure ligand conformetrics using NMR and establish their relationship to the target-bound conformation. These breakthroughs lie at the heart of the productivity of our drug discovery engine.