You Win Some, You Lose Some: Modifying the Molecular Periphery of Nitrofuran-Tagged Diazaspirooctane Reshapes Its Antibacterial Activity Profile.

The use of the concept of privileged structures significantly accelerates the search for new leads and their optimization. 6-(methylsulfonyl)-8-(4-methyl-4-1,2,4-triazol-3-yl)-2-(5-nitro-2-furoyl)-2,6-diazaspiro[3.4]octane has been identified as a lead, with MICs of 0.

Molecular Periphery Design Allows Control of the New Nitrofurans Antimicrobial Selectivity.

A series of 13 new 3-substituted 5-(5-nitro-2-furyl)-1,2,4-oxadiazoles was synthesized from different aminonitriles. All compounds were screened in the disc diffusion test at a 100 μg/mL concentration to determine the bacterial growth inhibition zone presence and diameter, and then the minimum inhibitory concentrations (MICs) were determined for the most active compounds by serial dilution. The compounds showed antibacterial activity against ESKAPE bacteria, predominantly suppressing the growth of 5 species out of the panel.

The Nitrofuran-Warhead-Equipped Spirocyclic Azetidines Show Excellent Activity against .

A series of 21 new 7'H-spiro[azetidine-3,5'-furo [3,4-d]pyrimidine]s substituted at the pyrimidine ring second position were synthesized. The compounds showed high antibacterial in vitro activity against . Two compounds had lower minimum inhibitory concentrations against (H37Rv strain) compared with isoniazid.

5-Nitrofuran-Tagged Oxazolyl Pyrazolopiperidines: Synthesis and Activity against ESKAPE Pathogens.

A series of eight 5-nitrofuran-tagged oxazolyl tetrahydropyrazolopyridines (THPPs) has been prepared in six stages with excellent regioselectivity. The testing of these compounds against pathogens of the ESKAPE panel showed a good activity of lead compound 1-(2-methoxyethyl)-5-(5-nitro-2-furoyl)-3-(1,3-oxazol-5-yl)-4,5,6,7-tetrahydro-1-pyrazolo[4,3-c] pyridine (), which is superior to nitrofurantoin. These results confirmed the benefit of combining a THPP scaffold with a nitrofuran warhead.

Exploration of Spirocyclic Derivatives of Ciprofloxacin as Antibacterial Agents.

The previously reported as well as newly synthesized derivatives of the 1-oxa-9-azaspiro[5.5]undecane were employed in the synthesis of thirty-six derivatives of ciprofloxacin using commercially available 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid and the literature protocol involving the preparation of boron chelate complex to facilitate nucleophilic aromatic substitution. All new fluoroquinolone derivatives were tested against two gram-positive as well as three gram-negative strains of bacteria.