Tetrahydronaphthyl azole oxime ethers: the conformationally rigid analogues of oxiconazole as antibacterials.
A series of novel (Z)- and (E)-2-imidazolo-/triazolo-methyl tetrahydronaphthyl oxime ethers (7-28) were synthesized as conformationally constrained analogues of oxiconazole and evaluated for antifungal and antibacterial activities. Many of these derivatives exhibited potent antibacterial activity and surprisingly none of them was active against fungal strains. The SAR studies showed that imidazole oxime ethers were more active than the corresponding triazole oxime ethers. Imidazole derivatives 8, 11, 12, 15, 18, 19, 21 and 23 exhibited high inhibitory activity with 1.56-0.39 microg/mL MIC values against Klebsiella pneumoniae, Escherichia coli and Staphylococcus aureus. These compounds represent new structure scaffolds that can be further optimized to give new antibacterial agents with structures significantly different from those of existing classes of antibiotics.
Bhandari
Kalpana
K
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226001, India. bhandarikalpana@rediffmail.com
Srinivas
Nagarapu
N
Shiva Keshava
G B
GB
Shukla
Praveen K
PK
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001393:Azoles; D001419:Bacteria / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects; D004987:Ethers / Q000138:chemical synthesis* / Q000494:pharmacology; D007093:Imidazoles; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology; D010091:Oximes; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D001393:Azoles; D004987:Ethers; D007093:Imidazoles; D009281:Naphthalenes; D010091:Oximes; C022155:oxiconazole