text: The publication of the NAPAP-fIIa crystal structure triggered many researches on thrombin inhibitors. NAPAP is an active site thrombin inhibitor. It fills the S3 and S2 pockets with its naphthalene and piperidine groups. AstraZeneca used the information to develop melagatran. The compound was poorly orally available, but after renovation they got a double prodrug which was the first oral DTI in clinical trials, ximelagatran. Ximelagatran was on the European market for approximately 20 months when it was suspended. Studies showed that treatment for over 35 days was linked with the risk of hepatic toxicity. It was never approved by the FDA.