Hit to Lead

Validated chemical classes will be selected for further hit appraisal. The prioritization will be based upon the initial potency, physical parameters such as solubility, lipophilicity, molecular weight, ligand efficiency/lipophilicity efficacy plots, synthetic availability and uniqueness (patentability). Furthermore, undesirable features will be identified (chemical instability, dependence on a toxicophore, metabolic vulnerabilities) and excluded upfront. Depending on the wishes of our clients we can include computational advice from leading CRO’s in this field and design the compounds to be synthesized based upon criteria described above.

In general our synthetic program will attempt to improve the on-target activity, while simultaneously balancing physical parameters such as solubility, lipophilicity, permeability and metabolic stability. Classes of compounds will be progressed to proof of concept in vivo efficacy. We also successfully participated in hit-to-lead programs for so-called multiple ligands (molecules active on several targets), resulting in two patent applications (5HTT/5HT2c and D2/H3, pending).