DESIGN AND CONSTRUCTION OF NOVEL THROMBIN INHIBITORS FEATURING P-3-P-4 QUATERNARY LACTAM DIPEPTIDE SURROGATES

Potent serine protease inhibitor la featuring a hybrid P-3-P-4 quatern ary lactam dipeptide surrogate was prepared based upon SAR and molecul ar modeling investigations and in order to further probe the S-2/S-3 t hrombin and FXa subsites. An efficient and concise synthetic route to the key aminolactam intermediate 4 was developed. The design, synthesi s, and biological activity of this target and its P-3-P-4 diastereomer Ib is presented. (C) 1998 Elsevier Science Ltd. All rights reserved.