New inhibitors of the complement system inspired in K76-COOH. A SAR study of filifolinol derivatives through modifications of the C3' position

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Summary *

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 classical complement pathway inhibitory activity was determined aiming to probe the importance of structural characteristics of the alicyclic part of K76-COOH. The results suggest that the diol moiety of the natural product may not be relevant for its activity, but useful for improving compound solubility. The presence and stereochemistry of O- and N- functionalities on C3’ may be relevant for biological activity of the filifolinol derivatives. The IC50 values of the most potent compounds were comparable or surpassed the activity of K76-COOH. Information provided by the agent in SIGEVA