RESUMEN
A series of trans-fused lactams containing the indane nucleus has been prepared. Compound 19 has much enhanced plasma stability compared with its lactone counterpart and shows appreciable in vitro anticoagulant activity.
Asunto(s)
Anticoagulantes/farmacología , Indanos/farmacología , Lactamas/farmacología , Trombina/antagonistas & inhibidores , Anticoagulantes/síntesis química , Sitios de Unión , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Indanos/síntesis química , Concentración 50 Inhibidora , Lactamas/síntesis química , Modelos Moleculares , Relación Estructura-ActividadRESUMEN
Synthesis of trans-fused lactones containing the indane nucleus has resulted in a series of potent acylating inhibitors of thrombin. As an example compound 11e has an apparent second order rate constant of 11 x 10(6) M(-1)sec(-1) for the inhibition of thrombin. The anticoagulant activity of these compounds is discussed.
Asunto(s)
Antitrombinas/farmacología , Indanos/química , Lactonas/farmacología , Anticoagulantes/síntesis química , Anticoagulantes/química , Anticoagulantes/farmacología , Antitrombinas/síntesis química , Antitrombinas/química , Humanos , Cinética , Lactonas/síntesis química , Lactonas/química , Tiempo de Tromboplastina ParcialRESUMEN
Synthesis of a variety of 5,5-trans fused lactones, related to compounds found in extracts of Lantana camara, has provided a series of novel acylating inhibitors of human thrombin, trypsin, chymotrypsin and human leucocyte elastase. The most effective thrombin inhibitor is 7 with an IC50 of 130 nM and a Kobs/[1] of 4,000 M-1 s-1.
