New Inhibitors of the Complement System Inspired in K76-COOH. A SAR Study of Filifolinol Derivatives Through Modifications of the C3' Position

LARGHI, E. L; OPERTO, M. A.; TORRES, R.; KAUFMAN, T. S.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Elsevier

Lugar: Amsterdam; Año: 2009 vol. 19 p. 6172 - 6175

0960-894X

A new series of tricyclic carboxylic acids with a 3H-spiro[benzofuran-2,10-cyclohexane] skeleton were synthesized from filifolinol, as analogs of the natural complement inhibitor K76-COOH. Their complement inhibitory activity was determined aiming to probe the importance of structural characteristics of the alicyclic part of K76-COOH. The presence and stereochemistry of O- and N-functionalities on C30 of the filifolinol derivatives are relevant for biological activity. The IC50 values of the most potent compounds were comparable or surpassed the activity of K76-COOH. The results also suggest that the diol moiety of the natural product may be useful for improving compound solubility.