New England PharmAssociates

Excellence in life sciences asset development

Case Studies

Medicinal chemistry solution for a stalled HTS hit-to-lead project

Company with antibacterial drug discovery program had screened a focused library to identify potent target inhibition but with no detectable antibacterial activity as measured by standard antibacterial assays against laboratory test strains and clinical isolates.


  • Review of data suggested physical chemical properties of screening hits might be preventing entry into bacterial cells
  • Devised a medicinal chemistry strategy to achieve drugable antibacterial activity to guide Lead Optimization.
  • Proposed series of new analogs that would test concept.
  • Reproducible antibacterial activity was detected following two iterations of analog synthesis.
  • Conclusions:
    Lead Optimization work on novel series of antibacterial agents enabled by new directions in synthetic strategy. The data produced enabled successful negotiations for out licensing the rejuvenated program.