191980-50-4Relevant academic research and scientific papers
Rhodium-catalysed conjugate addition of arylboronic acids to enantiopure dehydroamino acid derivatives
Hargrave, Jonathan D.,Bish, Gerwyn,Koehn, Gabriele Kociok,Frost, Christopher G.
experimental part, p. 5120 - 5125 (2010/12/25)
The rhodium-catalysed conjugate addition of arylboronic acids to an enantiopure acceptor derived from (R)-S-methylcysteine proceeds under substrate control to provide a range of functionalised phenylalanine derivatives with excellent stereocontrol via a highly diastereoselective protonation.
Design, synthesis, and binding affinities of pyrrolinone-based somatostatin mimetics
Smith III, Amos B.,Charnley, Adam K.,Mesaros, Eugen F.,Kikuchi, Osamu,Wang, Wenyong,Benowitz, Andrew,Chu, Chi-Lien,Feng, Jin-Jye,Chen, Kuo-Hsin,Lin, Atsui,Cheng, Fong-Chi,Taylor, Laurie,Hirschmann, Ralph
, p. 399 - 402 (2007/10/03)
(Chemical Equation Presented) Tetrapyrrolinone somatostatin (SRIF) mimetics (cf. 1), based on a heterochiral (D,L-mixed) pyrrolinone scaffold, were designed, synthesized, and evaluated for biological activity. The iterative synthetic sequence, incorporati
Structure-based design, synthesis and evaluation of conformationally constrained cysteine protease inhibitors
Scheidt, Karl A.,Roush, William R.,McKerrow, James H.,Selzer, Paul M.,Hansell, Elizabeth,Rosenthal, Philip J.
, p. 2477 - 2494 (2007/10/03)
The inhibition of cysteine proteases is being studied as a strategy to combat parasitic diseases such as Chagas' disease, leishmaniasis, and malaria. Cruzain is the major cysteine protease of Trypanosoma cruzi, the etiologic agent of Chagas' disease. A crystal structure of cruzain, covalently inactivated by fluoromethyl ketone inhibitor 1 (Cbz-Phe-Ala-FMK), was used as a template to design potential inhibitors. Conformationally constrained γ-lactams containing electrophilic aldehyde (12, 17, 18, 25, 26, and 29) or vinyl sulfone (43, 44, and 46) units were synthesized. Constrained lactam 26 had IC50 values of ca. 20nM against the Leishmania major protease and ca. 50nM versus falcipain, an important cysteine protease isolated from Plasmodium falciparum. However, all of the conformationally constrained inhibitors were weak inhibitors of cruzain, compared to unconstrained peptide aldehyde (e.g. 5 ) and vinyl sulfone inhibitors (e.g. 48, which proved to be an excellent inhibitor of cruzain with an apparent second order inhibition rate constant (k(inact)/K(i)) of 634,000s-1M-1). A significant reduction in activity was also observed with acyclic inhibitors 30 and 51 containing α-methyl phenylalanine residues at the P2 position. These data indicate that the pyrrolidinone ring, especially the quarternary center at P2, interferes with the normal substrate binding mode with cruzain, but not with falcipain or the leishmania protease. Copyright (C) 1998 Elsevier Science Ltd.
