1. Design and synthesis of potent and selective 5,6-fused heterocyclic thrombin inhibitors.
- Author
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Dominguez C, Duffy DE, Han Q, Alexander RS, Galemmo RA Jr, Park JM, Wong PC, Amparo EC, Knabb RM, Luettgen J, and Wexler RR
- Subjects
- Amidines chemical synthesis, Amidines pharmacology, Animals, Antithrombins chemical synthesis, Antithrombins pharmacology, Drug Design, Heterocyclic Compounds chemical synthesis, Heterocyclic Compounds pharmacology, Hydrogen Bonding, Indoles chemical synthesis, Indoles pharmacology, Molecular Structure, Rats, Amidines chemistry, Antithrombins chemistry, Heterocyclic Compounds chemistry, Indoles chemistry
- Abstract
Thrombin, a serine protease, plays a central role in the initiation of thrombotic events. We report the design, synthesis, and antithrombotic efficacy of XU817 (7), a nonpeptide 5-(amidino) indole thrombin inhibitor. Utilizing the co-crystal structure of XU817 bound in the active site of thrombin we were able to synthesize analogs with enhanced thrombin affinity.
- Published
- 1999
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