Prodrugs pp 889-922 | Cite as

Prodrugs of Benzamidines

  • Jefferson W. Tilley
Part of the Biotechnology: Pharmaceutical Aspects book series (PHARMASP, volume V)


Benzamidines figure prominently as pharmacophores in several classes of drugs. These include anti-infectives such as anti-parasitic (Clement and Raether, 1985), anti-bacterial (Lamb and White, 1939), and anti-malarial (Leban et al., 2004) agents, alphaIIb-betaIIIa integrin antagonists (Weller et al., 1996), and inhibitors of the proteases factor VIIa (Parlow et al., 2003) and factor Xa (Pinto et al., 2001). Several have demonstrated utility in human studies; among these, pentamidine (1) is a prototype of a class of DNA minor grove binding agents that are effective for the treatment of African trypanosomiasis and leishmanisis as well as the opportunistic infection pneumocystis carnii pneumonia prevalent among AIDS patients. Pentamidine, which is administered by aerosol, was introduced to the United States market for p. carnii in 1989. Furamidine (2) is currently undergoing clinical trials as an orally active prodrug of the corresponding bisamidine (3) for the same indication. Among others, sibrafiban (4) (Cases et al., 1999;
Dooley and Goa, 1999) and lefradafiban (6) (Muller et al., 1997) are orally active prodrugs for the benzamidines 5 and 7, which are clinically efficacious as platelet aggregation inhibitors.


Platelet Aggregation Oral Activity Active Prodrug Platelet Aggregation Assay Active Thrombin Inhibitor 
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Copyright information

© American Association of Pharmaceutical Scientists 2007

Authors and Affiliations

  • Jefferson W. Tilley
    • 1
  1. 1.Roche Research CenterNutley

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