37763-24-9Relevant academic research and scientific papers
Design, synthesis, and SAR of a series of activated protein C (APC) inhibitors with selectivity against thrombin for the treatment of haemophilia
Bach, Peter,Knerr, Laurent,Fjellstr?m, Ola,Hansson, Kenny,Mattsson, Christer,Gustafsson, David
, p. 821 - 827 (2014/02/14)
A design strategy was used to identify inhibitors of activated protein C with selectivity over thrombin featured by a basic and/or aromatic functionality for binding to the S2 pocket. Our strongest inhibitor showed an IC 50-material value and selectivity for APC vs thrombin similar to a compound previously reported in the literature. However, in contrast to the reference compound, our compound showed a retained coagulant effect of thrombin with increasing substrate concentration in a modified Calibrated Automated Thrombogram (CAT) method. This was likely related to our compound being inactive against FVIIa, while the reference compound showed an IC50 of 8.9 μM. Thus, the higher selectivity of our compound against all relevant coagulation factors likely explained its higher therapeutic potential in comparison to the reference compound. The data indicate that at least a 100-fold selectivity over other serine proteases in the coagulation cascade will be required for an effective APC inhibitor.
Organocatalytic synthesis of optically active β-branched α-amino esters via asymmetric biomimetic transamination
Su, Cunxiang,Xie, Ying,Pan, Hongjie,Liu, Mao,Tian, Hua,Shi, Yian
, p. 5856 - 5860 (2014/08/05)
This paper describes an efficient asymmetric biomimetic transamination of α-keto esters with a quinine-derived chiral base as the catalyst, giving a variety of β-branched α-amino esters in 50-96% yield and 87-95% ee. This journal is the Partner Organisations 2014.
Synthesis of novel potent hepatitis C virus NS3 protease inhibitors: Discovery of 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a N-acyl-l-hydroxyproline bioisostere
Thorstensson, Fredrik,Wangsell, Fredrik,Kvarnstroem, Ingemar,Vrang, Lotta,Hamelink, Elizabeth,Jansson, Katarina,Hallberg, Anders,Rosenquist, Asa,Samuelsson, Bertil
, p. 827 - 838 (2007/10/03)
Potent tetrapeptidic inhibitors of the HCV NS3 protease have been developed incorporating 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a new N-acyl-l-hydroxyproline mimic. The hydroxycyclopentene template was synthesized in eight steps from commercially available (syn)-tetrahydrophthalic anhydride. Three different amino acids were explored in the P1-position and in the P2-position the hydroxyl group of the cyclopentene template was substituted with 7-methoxy-2-phenyl-quinolin-4-ol. The P3/P4-positions were then optimized from a set of six amino acid derivatives. All inhibitors were evaluated in an in vitro assay using the full-length NS3 protease. Several potent inhibitors were identified, the most promising exhibiting a Ki value of 1.1 nM.
ENANTIOSPECIFIC SYNTHESIS OF A RIGID, C2 SYMMETRIC, CHIRAL GUANIDINE BY A NEW AND DIRECT METHOD
Corey, E. J.,Ohtani, Mitsuaki
, p. 5227 - 5230 (2007/10/02)
A broadly applicable method has been demonstrated for the efficient synthesis of chiral bicyclic guanidines such as 1 from chiral α-amino acids.
