Design and synthesis of benzoazepinone-derived cyclic malonamides and aminoamides as potent gamma-secretase inhibitors.

We report the synthesis of benzoazepine-derived cyclic malonamides (2) and aminoamides (3) as gamma-secretase inhibitors for the potential treatment of Alzheimer's disease. The in vitro structure-activity relationships of 2 and 3 along with dog pharmacokinetic results are described.

5-Amidinobenzo[b]thiophenes as dual inhibitors of factors IXa and Xa.

Syntheses and SAR studies of 5-amidinobenzo[b]thiophene analogs provided compounds with low submicromolar factor IXa activity and equal or slightly better selectivity relative to factor Xa.

5-Amidinoindoles as dual inhibitors of coagulation factors IXa and Xa.

Structural features of a 5-amidinoindole inhibitor of factor Xa, which displayed modest inhibition of factor IXa were varied to increase potency and improve selectivity for factor IXa.