Nonclassical Zwitterions as a Design Principle to Reduce Lipophilicity without Impacting Permeability
Henrik Möbitz,
Birger Dittrich,
Stephane Rodde
et al.
Abstract:The ionization of bioactive molecules impacts many ADME-relevant
physicochemical properties, in particular, solubility, lipophilicity,
and permeability. Ampholytes contain both acidic and basic groups
and are distinguished as ordinary ampholytes and zwitterions. An influential
review states that zwitterions only exist if the acidic pK
a is significantly lower than the basic pK
a. Through concordance of measured and calculated pK
a and log P, we show that the
zwitterionic behavior of several marketed drugs and … Show more
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