Lipophilic efficiency indices such as LLE and LELP were introduced supporting balanced optimization of potency and ADME profile. Analyzing the impact of these metrics on ADME and safety properties and binding thermodynamics we found that both LLE and LELP help identifying better quality compounds. LLE is sensible for the development stages but does not prefer fragment-type hits, while LELP has advantage on this class of compounds and discriminates preferred starting points effectively. Both LLE and LELP have significant impact on ADME and safety profiles, however LELP outperforms LLE in risk assessment. Our results suggest that monitoring lipophilic efficiency metrics could contribute significantly to compound quality and might improve the output of medicinal chemistry programs.

Impact of lipophilic efficiency on compound quality

244th National Meeting (2012)

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