title: 4-Aminothiazolyl analogs of GE2270 A: design, synthesis and evaluation of imidazole analogs.
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.
authors.affiliation: Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA. matthew.lamarche@novartis.com
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: LaMarche
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Leeds
authors.forename: JoAnne
authors.initials: J
authors.lastname: Dzink-Fox
authors.forename: Steve
authors.initials: S
authors.lastname: Mullin
authors.forename: Michael A
authors.initials: MA
authors.lastname: Patane
authors.forename: Elin M
authors.initials: EM
authors.lastname: Rann
authors.forename: Stacey
authors.initials: S
authors.lastname: Tiamfook
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D003300:Copper / Q000737:chemistry; D004926:Escherichia coli / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000588:Amines; D000900:Anti-Bacterial Agents; D007093:Imidazoles; D010456:Peptides, Cyclic; D013844:Thiazoles; D003300:Copper; C068122:GE 2270 A