135064-58-3Relevant academic research and scientific papers
New proline mimetics: Synthesis of thrombin inhibitors incorporating cyclopentane- and cyclopentenedicarboxylic acid templates in the P2 position. Binding conformation investigated by X-ray crystallography
N?teberg, Daniel,Br?nalt, Jonas,Kvarnstr?m, Ingemar,Linschoten, Marcel,Musil, Djordje,Nystr?m, Jan-Erik,Zuccarello, Guido,Samuelsson, Bertil
, p. 1705 - 1713 (2007/10/03)
With the aim to prepare nonpeptidic thrombin inhibitors, the amino acids of the thrombin-inhibiting tripeptide chain D-Phe-Pro-Arg were replaced with isosteres. Arg was replaced with the more rigid P1 truncated p- amidinobenzylamine (Pab), Pro with either cyclopentane-1,2-dicarboxylic acid or cyclopentene-1,5-dicarboxylic acid, and D-Phe with a series of readily available lipophilic amines. One of the most potent compounds (25, pIC50 = 6.01) in these series was cocrystallized with thrombin where the X-ray crystal structure provide insight to the structure-activity relationship (SAR).
