Microbial Hydroxylation of Lead Compounds; a Way out of the Lipophilic Cul-de-sac

Presented at: RICT meeting, 2014, Rouen, France

Microbial biotransformation offers an alternative and complementary approach to synthetic medicinal chemistry for the structural diversification of hit or lead compounds. Hypha Discovery has a scalable microbial process effective for activating C-H bonds to achieve aliphatic and aromatic hydroxylation. Applications include boosting ligand lipophilicity efficiency, improving selectivity, exploring SAR, creating handles for further derivatisation (e.g. fluorination for PET ligand formation or to block metabolism), or simply to highlight the conversion into active mammalian metabolites.

This poster features a case study describing the biotransformation of a kinase inhibitor to explore lead diversification using Hypha’s microbial panel. One of the derivatives possessed a reduced logD and an unpredicted 20-fold increase in potency, resulting in an increase in the LLE of 2.6 units. The process provides a scalable and reproducible way to access greater quantities of metabolites for further characterisation.