277751-22-1Relevant academic research and scientific papers
A cyclopent-2-enecarbonyl group mimics proline at the P2 position of prolyl oligopeptidase inhibitors
Jarho, Elina M.,Ven?l?inen, Jarkko I.,Huuskonen, Juhani,Christiaans, Johannes A. M.,Garcia-Horsman, J. Arturo,Forsberg, Markus M.,J?rvinen, Tomi,Gynther, Jukka,M?nnist?, Pekka T.,Wallén, Erik A. A.
, p. 5605 - 5607 (2007/10/03)
With the aim to replace the natural amino acid proline by a proline mimetic structure, a cyclopent-2-enecarbonyl moiety was studied at the P2 position of prolyl oligopeptidase (POP) inhibitors. The cyclopent-2-enecarbonyl moiety proved to be an excellent proline mimetic at the P2 position of POP inhibitors. The replacement is particularly useful when increased lipophilicity is needed.
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).
