Thrombin inhibitors based on [5,5] trans-fused indane lactams

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Pharmacology

Background:

• Lactam and lactone structures are common in biologically active molecules.
• Indane derivatives have shown diverse pharmacological properties.
• Developing stable anticoagulant agents remains a significant therapeutic challenge.

Purpose of the Study:

• To synthesize and characterize novel trans-fused lactam compounds incorporating the indane nucleus.
• To evaluate the plasma stability and in vitro anticoagulant activity of these novel lactams.
• To compare the properties of the synthesized lactams with their corresponding lactone analogs.

Main Methods:

• Multi-step organic synthesis to prepare a series of trans-fused lactams.
• Characterization of synthesized compounds using spectroscopic techniques.
• In vitro assays to assess plasma stability and anticoagulant activity (e.g., Prothrombin Time, Activated Partial Thromboplastin Time).

Main Results:

• Successful synthesis of a series of trans-fused lactams containing the indane moiety.
• Compound 19 exhibited significantly enhanced plasma stability compared to its lactone counterpart.
• Compound 19 demonstrated appreciable in vitro anticoagulant activity.

Conclusions:

• Trans-fused lactams based on the indane nucleus represent a promising class of compounds.
• The enhanced plasma stability of Compound 19 suggests potential for improved pharmacokinetic profiles.
• These findings warrant further investigation into the therapeutic potential of these novel lactam derivatives as anticoagulants.