Improvement in aqueous solubility of achiral symmetric cyclofenil by modification to a chiral asymmetric analog.

ABSTRACT: Decreasing the partition coefficient (LogP) by the introduction of a hydrophilic group is the conventional approach for improving the aqueous solubility of drug candidates, but is not always effective. Since melting point is related to aqueous solubility, we and other groups have developed alternative strategies to improve solubility by means of chemical modification to weaken intermolecular interaction in the solid state, thereby lowering the melting point and increasing the solubility. Here, we show that converting the symmetrical molecular structure of the clinically used estrogen receptor (ER) antagonist cyclofenil (1) into asymmetrical form by introducing an alkyl group enhances the aqueous solubility. Among the synthesized analogs, the chiral methylated analog (R)-4c shows the highes

SUBMITTER: Morimoto J 

PROVIDER: S-EPMC8209153 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature