Exploration of Potential Prodrugs of RWJ‐445167, an Oxyguanidine‐based Dual Inhibitor of Thrombin and Factor Xa

@article{Maryanoff2006ExplorationOP,
  title={Exploration of Potential Prodrugs of RWJ‐445167, an Oxyguanidine‐based Dual Inhibitor of Thrombin and Factor Xa},
  author={Bruce E. Maryanoff and David F. McComsey and Michael J. Costanzo and Stephen C. Yabut and Tianbao Lu and Mark R. Player and Edward C. Giardino and Bruce P. Damiano},
  journal={Chemical Biology \& Drug Design},
  year={2006},
  volume={68}
}
Compound 2 (RWJ‐445167; 3DP‐10017), a dual inhibitor of thrombin and factor Xa, was advanced into human clinical studies. However, its oral bioavailability in humans proved to be below acceptable limits. To address this issue, we explored a prodrug approach involving numerous guanidine derivatives. Prodrug candidates of classes A (carbamate derivatives), B (imidate derivatives), and C (alkyl and acyl derivatives), compounds 3–6, were synthesized and evaluated for anticoagulant activity at 2h… 
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