Zoliflodacin

InvivoChem Cat #:V4277CAS #:1620458-09-4Purity >=98%

Description: Zoliflodacin (also known as ETX0914 and AZD0914) is a novel and potent spiropyrimidinetrione bacterial DNA gyrase/topoisomerase inhibitor. Zoliflodacin has potent in vitro antibacterial activity against Gram-positive and Gram-negative organisms, including S. aureus with the MIC90 of 0.25 ug/mL. AZD0914 has potent in vitro antibacterial activity against key Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus agalactiae), fastidious Gram-negative (Haemophilus influenzae and Neisseria gonorrhoeae), atypical (Legionella pneumophila), and anaerobic (Clostridium difficile) bacterial species, including isolates with known resistance to fluoroquinolones. AZD0914 works via inhibition of DNA biosynthesis and accumulation of double-strand cleavages; this mechanism of inhibition differs from those of other marketed antibacterial compounds. AZD0914 stabilizes and arrests the cleaved covalent complex of gyrase with double-strand broken DNA under permissive conditions and thus blocks religation of the double-strand cleaved DNA to form fused circular DNA. Whereas this mechanism is similar to that seen with fluoroquinolones, it is mechanistically distinct. AZD0914 exhibited low frequencies of spontaneous resistance in S. aureus, and if mutants were obtained, the mutations mapped to gyrB. Additionally, no cross-resistance was observed for AZD0914 against recent bacterial clinical isolates demonstrating resistance to fluoroquinolones or other drug classes, including macrolides, beta-lactams, glycopeptides, and oxazolidinones. AZD0914 was bactericidal in both minimum bactericidal concentration and in vitro time-kill studies. In in vitro checkerboard/synergy testing with 17 comparator antibacterials, only additivity/indifference was observed. The potent in vitro antibacterial activity (including activity against fluoroquinolone-resistant isolates), low frequency of resistance, lack of cross-resistance, and bactericidal activity of AZD0914 support its continued development.

Description:

References: Antimicrob Agents Chemother. 2015 Jan; 59(1):467-74.

References:

-20C for 3 years in powder form

Synonym: ETX0914; ETX-0914; ETX 0914; AZD0914; AZD-0914; AZD 0914.
IUPAC/Chemical Name: (2R, 4S, 4aS)-11-fluoro-2, 4-dimethyl-8-((S)-4-methyl-2-oxooxazolidin-3-yl)-1, 2, 4, 4a-tetrahydro-2'H, 6H-spiro[isoxazolo[4, 5-g][1, 4]oxazino[4, 3-a]quinoline-5, 5'-pyrimidine]-2', 4', 6'(1'H, 3'H)-trione
InChi Key: ZSWMIFNWDQEXDT-ZESJGQACSA-N
InChi Code: InChI=1S/C22H22FN5O7/c1-8-7-33-21(32)28(8)17-12-4-11-5-22(18(29)24-20(31)25-19(22)30)16-10(3)34-9(2)6-27(16)14(11)13(23)15(12)35-26-17/h4, 8-10, 16H, 5-7H2, 1-3H3, (H2, 24, 25, 29, 30, 31)/t8-, 9+, 10-, 16+/m0/s1
SMILES Code: O=C(NC(C12[C]([CH](C)O[CH](C)C3)([H])N3C4=C(F)C(ON=C5N6C(OC[CH]6C)=O)=C5C=C4C2)=O)NC1=O