Processes and compounds for the preparation of substituted...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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C548S254000

Reexamination Certificate

active

11339802

ABSTRACT:
The present invention provides processes for the preparation of substituted naphthylindole derivatives that can be used as inhibitors of plasminogen activator inhibitor-1(PAI-1). In certain embodiments of the invention, the processes involve reactions that include one or more of an Oppenauer oxidation, a Fischer indole synthesis, a methyl ether cleavage, or coupling a substituted methyltetrazole with a substituted naphthol.

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Biemond et al., “Thyrombolysis and Reocclusion in Experimental Jugular Vein and Coronary Artery Thrombosis: Effects of a Plasminogen Activator Inhibitor Type 1-Neutralizing Monoclonal Antibody,”Circulation,1995, 91(4), 1175-1181.
Carmeliet et al., “Plasminogen Activator Inhibitor-1 Gene-deficient Mice; II. Effects of hemostasis, Thrombosis, and Thrombolysis,”Journal of Clinical Invest.,1993, 92, 2756-2760.
Daci et al., “Mice Lacking the Plasminogen Activator Inhibitor 1 Are Protected from Trabecular Bone Loss Induced by Estrogen Deficiency,”Journal of Bone&Mineral Research,2000, 15(8), 1510-1516.
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Nordt et al., “Differential Regulation by Troglitazone of Plasminogen Activator Inhibitor Type 1 in Human Hepatic and Vascular Cells,”The Journal of Clinical Endocrinology&Metabolism,2000, 85(4), 1563-1568.
Reilly et al., “Both Circulating and Clot-Bound Plasminogen Activator Inhibitor-1 Inhibit Endogenous Fibrolysis in the Rat,”Arteriosclerosis&Thrombosis,1991, 11, 1276-1286.
Rocha et al., “The Relationship Between Impaired Fribinolysis and Coronary Heart Disease: a Role for PAI-1,”Fibrinolysis,1994, 8, 294-303.

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