Oxyguanidines. Part 2: Discovery of a novel orally active thrombin inhibitor through structure-based drug design and parallel synthesis.
Lu T,
Markotan T,
Coppo F,
Tomczuk B,
Crysler C,
Eisennagel S,
Spurlino J,
Gremminger L,
Soll RM,
Giardino EC,
Bone R.
3-Dimensional Pharmaceuticals, Inc., 665 Stockton Drive, Exton, PA 19341, USA. tlu3@prdus.jnj.com
Through structure-based drug design and parallel synthesis, we have discovered a novel series of nonpeptidic phenyl-based thrombin inhibitors using oxyguanidines as guanidine bioisosteres. These compounds have been found to be highly potent, highly selective, and orally bioavailable.
PMID: 15203151 [PubMed - indexed for MEDLINE]