147267-14-9Relevant academic research and scientific papers
O-benzyl hydroxyproline as a bioisostere for Phe-Pro: Novel dipeptide thrombin inhibitors
Klein, Scott I.,Dener, Jeffrey M.,Molino, Bruce F.,Gardner, Charles J.,D'Alisa, Rose,Dunwiddie, Christopher T.,Kasiewski, Charles,Leadley, Robert J.
, p. 2225 - 2230 (1996)
A series of analogs were prepared based on the known thrombin inhibitor PPACK, in which the D-Phe-Pro dipeptide has been replaced by trans-4-O-benzyl hydroxyproline. One of these analogs is a more potent inhibitor of thrombin, and is more selective, than PPACK itself.
Potent and fully noncompetitive peptidomimetic inhibitor of multidrug resistance P-glycoprotein
Arnaud, Ophélie,Koubeissi, Ali,Ettouati, Laurent,Terreux, Rapha?l,Alamé, Ghina,Grenot, Catherine,Dumontet, Charles,Di Pietro, Attilio,Paris, Jo?lle,Falson, Pierre
supporting information; experimental part, p. 6720 - 6729 (2010/11/16)
Nα-Boc-l-Asp(OBn)-l-Lys(Z)-OtBu (reversin 121, 1), an inhibitor of the P-gp ABC transporter, was used to conceive compounds inhibiting the drug efflux occurring through the Hoechst 33342 and daunorubicin transport sites of P-gp, respectively H and R sites. Replacement of the aspartyl residue by trans-4-hydroxy-l-proline (4(R)Hyp) gave compounds 11 and 15 characterized by half-maximal inhibitory concentrations (IC50) of 0.6 and 0.2 μM, which are 2-and 7-fold lower than that of the parent molecule. The difference in IC50 between 11 and 15 rests on the carbonyl group of the peptidyl bond, reduced in 15. Those compounds are rather specific of P-gp, having no or limited activity on MRP1 and BCRP. 15 displayed no marked cytotoxicity up to 10-fold its IC50. Importantly, 15 equally inhibited the Hoechst 33342 and daunorubicin effluxes through a typical noncompetitive inhibition mechanism, suggesting its binding to a site different from the H and R drug-transport sites.
Discovery of inhibitors of the channel-activating protease prostasin (CAP1/PRSS8) utilizing structure-based design
Tully, David C.,Vidal, Agnes,Chatterjee, Arnab K.,Williams, Jennifer A.,Roberts, Michael J.,Petrassi, H. Michael,Spraggon, Glen,Bursulaya, Badry,Pacoma, Reynand,Shipway, Aaron,Schumacher, Andrew M.,Danahay, Henry,Harris, Jennifer L.
scheme or table, p. 5895 - 5899 (2009/05/31)
Structure-based design was utilized to guide the early stage optimization of a substrate-like inhibitor to afford potent peptidomimetic inhibitors of the channel-activating protease prostasin. The first X-ray crystal structures of prostasin with small molecule inhibitors bound to the active site are also reported.
