Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT
Zur Ablage hinzufügen
  Lokale TagsFreigabegeschichteDetailsÜbersicht

Freigegeben
Zeitschriftenartikel

Synthesis and Characterization of Phenylalanine Amides Active against Mycobacterium abscessus and Other Mycobacteria

MPG-Autoren
/persons/resource/persons58578

Goddard,  Richard
Service Department Lehmann (EMR), Max-Planck-Institut für Kohlenforschung, Max Planck Society;

/persons/resource/persons58981

Schulze,  Philipp
Service Department Schulze (GC, HPLC), Max-Planck-Institut für Kohlenforschung, Max Planck Society;

Externe Ressourcen
Es sind keine externen Ressourcen hinterlegt
Volltexte (beschränkter Zugriff)
Für Ihren IP-Bereich sind aktuell keine Volltexte freigegeben.
Volltexte (frei zugänglich)
Es sind keine frei zugänglichen Volltexte in PuRe verfügbar
Ergänzendes Material (frei zugänglich)
Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar
Zitation

Lang, M., Ganapathy, U. S., Mann, L., Abdelaziz, R., Seidel, R. W., Goddard, R., et al. (2023). Synthesis and Characterization of Phenylalanine Amides Active against Mycobacterium abscessus and Other Mycobacteria. Journal of Medicinal Chemistry, 66(7), 5079-5098. doi:10.1021/acs.jmedchem.3c00009.


Zitierlink: https://hdl.handle.net/21.11116/0000-000D-068B-0
Zusammenfassung
Nα-2-thiophenoyl-d-phenylalanine-2-morpholinoanilide [MMV688845, Pathogen Box; Medicines for Malaria Venture; IUPAC: (2R)-N-(1-((2-morpholinophenyl)amino)-1-oxo-3-phenylpropan-2-yl)thiophene-2-carboxamide)] is a hit compound, which shows activity against Mycobacterium abscessus (MIC90 6.25–12.5 μM) and other mycobacteria. This work describes derivatization of MMV688845 by introducing a thiomorpholine moiety and the preparation of the corresponding sulfones and sulfoxides. The molecular structures of three analogs are confirmed by X-ray crystallography. Conservation of the essential R configuration during synthesis is proven by chiral HPLC for an exemplary compound. All analogs were characterized in a MIC assay against M. abscessus, Mycobacterium intracellulare, Mycobacterium smegmatis, and Mycobacterium tuberculosis. The sulfone derivatives exhibit lower MIC90 values (M. abscessus: 0.78 μM), and the sulfoxides show higher aqueous solubility than the hit compound. The most potent derivatives possess bactericidal activity (99% inactivation of M. abscessus at 12.5 μM), while they are not cytotoxic against mammalian cell lines.