13018-45-6Relevant academic research and scientific papers
ASYMMETRIC HYDROGENATIONS OF N-PYRUVOYL-(S)-AMINO ACID ESTERS BY USING SODIUM BOROHYDRIDE. A SOLVENT EFFECT
Munegumi, Toratane,Harada, Kaoru
, p. 1225 - 1228 (1983)
N-Pyruvoyl-(S)-amino acid isobutyl esters were hydrogenated with sodium borohydride(NBH) in several alcoholic solvents, and N--(S)-amino acid esters were obtained with diastereoisomeric purity of up to 44percent.Significant solvent effect on
PROTEASOME INHIBITORS
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Paragraph 0196; 0199, (2019/11/19)
The disclosure provides proteasome inhibitors that can be used to halt cell division of rapidly dividing cells by preventing the degradation of cell cycle-regulating proteins, such as cyclins, cyclin-dependent kinase inhibitors, and p53. The proteasome in
Design, synthesis, and evaluation of cystargolide-based β-lactones as potent proteasome inhibitors
Niroula, Doleshwar,Hallada, Liam P.,Le Chapelain, Camille,Ganegamage, Susantha K.,Dotson, Devon,Rogelj, Snezna,Groll, Michael,Tello-Aburto, Rodolfo
supporting information, p. 962 - 977 (2018/09/04)
The peptidic β-lactone proteasome inhibitors (PIs) cystargolides A and B were used to conduct structure-activity relationship (SAR) studies in order to assess their anticancer potential. A total of 24 different analogs were designed, synthesized and evaluated for proteasome inhibition, for cytotoxicity towards several cancer cell lines, and for their ability to enter intact cells. X-ray crystallographic analysis and subunit selectivity was used to determine the specific subunit binding associated with the structural modification of the β-lactone (P1), peptidic core, (Px and Py), and end-cap (Pz) of our scaffold. The cystargolide derivative 5k, structurally unique at both Py and P1, exhibited the most promising inhibitory activity for the β5 subunit of human proteasomes (IC50 = 3.1 nM) and significant cytotoxicity towards MCF-7 (IC50 = 416 nM), MDA-MB-231 (IC50 = 74 nM) and RPMI 8226 (IC50 = 41 nM) cancer cell lines. Cellular infiltration assays revealed that minor structural modifications have significant effects on the ability of our PIs to inhibit intracellular proteasomes, and we identified 5k as a promising candidate for continued therapeutic studies. Our novel drug lead 5k is a more potent proteasome inhibitor than carfilzomib with mid-to-low nanomolar IC50 measurements and it is cytotoxic against multiple cancer cell lines at levels approaching those of carfilzomib.
ASYMMETRIC HYDROGENATIONS OF N-PYRUVOYL-(S)-AMINO ACID ESTERS.
Harada,Munegumi
, p. 2774 - 2777 (2007/10/02)
N- left bracket (R)-Lactoyl right bracket -(S)-amino acid isobutyl esters were obtained with a diastereoisomeric purity up to 34%, through the catalytic hydrogenations of N-pyruvoyl-(S)-amino acid (alanine, valine, and leucine) isobutyl esters over pallad
