Synthesis of novel 5-amino-thiazolo[4,5-d]pyrimidines as E. coli and S. aureus SecA inhibitors

Mi-Yeon Jang; Steven De Jonghe; Kenneth Segers; Jozef Anné; Piet Herdewijn

doi:10.1016/j.bmc.2010.10.027

Synthesis of novel 5-amino-thiazolo[4,5-d]pyrimidines as E. coli and S. aureus SecA inhibitors

Bioorg Med Chem. 2011 Jan 1;19(1):702-14. doi: 10.1016/j.bmc.2010.10.027. Epub 2010 Oct 19.

Authors

Mi-Yeon Jang¹, Steven De Jonghe, Kenneth Segers, Jozef Anné, Piet Herdewijn

Affiliation

¹ Katholieke Universiteit Leuven, Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, Minderbroedersstraat 10, 3000 Leuven, Belgium.

PMID: 21094610
DOI: 10.1016/j.bmc.2010.10.027

Abstract

An efficient synthesis of a library of 5-amino-thiazolo[4,5-d]pyrimidines is reported. Regioselective displacements of chlorines, as well as regioselective diazotation reactions are described, which allow the introduction of structural diversity on the scaffold by consecutive reactions. Screening of this focused library led to the discovery of SecA inhibitors from Escherichia coli and Staphylococcus aureus.

MeSH terms

Adenosine Triphosphatases / antagonists & inhibitors*
Bacterial Proteins / antagonists & inhibitors*
Escherichia coli / enzymology*
Magnetic Resonance Spectroscopy
Mass Spectrometry
Membrane Transport Proteins
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacology*
SEC Translocation Channels
SecA Proteins
Staphylococcus aureus / enzymology*

Substances

Bacterial Proteins
Membrane Transport Proteins
Pyrimidines
SEC Translocation Channels
Adenosine Triphosphatases
SecA Proteins