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4-Aminothiazolyl analogs of GE2270 A: design, synthesis and evaluation of imidazole analogs
Authors:LaMarche Matthew J  Leeds Jennifer A  Dzink-Fox JoAnne  Mullin Steve  Patane Michael A  Rann Elin M  Tiamfook Stacey
Institution:a Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA
b Infectious Disease Area, Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA
Abstract:Imidazole analogs of the antibiotic natural product GE2270 A (1) were designed, synthesized, and evaluated for Gram positive bacteria growth inhibition. A recently reported, copper-mediated synthesis was exploited to prepare 4-thiazolyl imidazole analogs of 1. The synthesis described represents a structurally complex, natural product-based application of this recently reported synthetic methodology. In addition, the biological evaluation of the imidazole-based analogs further define the SAR of the 4-aminothiazolyl-based antibacterial template.
Keywords:MIC  minimum inhibitory concentration  G+  gram positive  MRSA  methicillin resistant staphylococci  VRE  vancomycin resistant enterococci  S  aureus  Staphylococcus aureus  E  faecalis  Enterrococcus faecalis  E  faecium  Enterococcus faecium  S  pyogenes  Streptococcus pyogenes  EF-Tu  elongation factor Tu
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