4-Aminothiazolyl analogs of GE2270 A: design, synthesis and evaluation of imidazole analogs

Matthew J LaMarche; Jennifer A Leeds; JoAnne Dzink-Fox; Steve Mullin; Michael A Patane; Elin M Rann; Stacey Tiamfook

doi:10.1016/j.bmcl.2011.04.048

4-Aminothiazolyl analogs of GE2270 A: design, synthesis and evaluation of imidazole analogs

Bioorg Med Chem Lett. 2011 Jun 1;21(11):3210-5. doi: 10.1016/j.bmcl.2011.04.048. Epub 2011 Apr 21.

Authors

Matthew J LaMarche¹, Jennifer A Leeds, JoAnne Dzink-Fox, Steve Mullin, Michael A Patane, Elin M Rann, Stacey Tiamfook

Affiliation

¹ Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA. [email protected]

PMID: 21550238
DOI: 10.1016/j.bmcl.2011.04.048

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.

MeSH terms

Amines / chemical synthesis*
Amines / chemistry
Amines / pharmacology
Anti-Bacterial Agents* / chemical synthesis
Anti-Bacterial Agents* / pharmacology
Copper / chemistry
Escherichia coli / drug effects
Gram-Positive Bacteria / drug effects*
Imidazoles / chemical synthesis
Imidazoles / chemistry*
Imidazoles / pharmacology
Microbial Sensitivity Tests
Molecular Structure
Peptides, Cyclic / chemistry*
Peptides, Cyclic / pharmacology
Structure-Activity Relationship
Thiazoles / chemical synthesis*
Thiazoles / chemistry
Thiazoles / pharmacology

Substances

Amines
Anti-Bacterial Agents
Imidazoles
Peptides, Cyclic
Thiazoles
Copper
GE 2270 A