1312473-63-4

1312473-63-4 structure

Name: PF-5081090
Chemical Name: (2R)-4-[4-(2-fluoro-4-methoxyphenyl)-2-oxopyridin-1-yl]-N-hydroxy-2-methyl-2-methylsulfonylbutanamide
CAS Number: 1312473-63-4
Molecular Formula: C₁₈H₂₁FN₂O₆S
Molecular Weight: 412.43300
Catalog: Signaling Pathways Anti-infection Bacterial
Create Date: 2017-02-19 17:50:46
Modify Date: 2024-01-09 15:16:24
PF-5081090 (LpxC-4) is a potent LpxC inhibitor, is a rapidly bactericidal with broad-spectrum activity. PF-5081090 serves as a regulator of lipid A biosynthesis in Gram-negative pathogens[1][2].

Name	(2R)-4-[4-(2-fluoro-4-methoxyphenyl)-2-oxopyridin-1-yl]-N-hydroxy-2-methyl-2-methylsulfonylbutanamide
Synonyms	(\|AR)-4-(2-Fluoro-4-methoxyphenyl)-N-hydroxy-\|A-methyl-\|A-(methylsulfonyl)-2-oxo-1(2H)-pyridinebutanamide MS 245 oxalate

Description	PF-5081090 (LpxC-4) is a potent LpxC inhibitor, is a rapidly bactericidal with broad-spectrum activity. PF-5081090 serves as a regulator of lipid A biosynthesis in Gram-negative pathogens[1][2].
Related Catalog	Research Areas >> Infection Signaling Pathways >> Anti-infection >> Bacterial
In Vitro	PF-5081090 shows strong potency against a broad spectrum of Gram-negative pathogens with IC50s of 1.1 nM (P. aeruginosa), 0.069 nM (K. pneumonia) and MIC90s of 1 μg/mL (P. aeruginosa, K. pneumoniae), 0.25 μg/mL (E. coli), 0.5 μg/mL (Enterobacter spp), 2 μg/mL (S. maltophilia)[1]. PF-5081090 (0.25 μg/mL; 0-50 h) demonstrates sustained bactericidal activities against P. aeruginosa UC12120 (A), PA-1955 (B), and K. pneumoniae KP-1487[1]. PF-5081090 (32 mg/L) increases antibiotic susceptibility in Acinetobacter baumannii with rifampicin, vancomycin, azithromycin, imipenem and amikacin[2]. PF-5081090 (32 mg/L) inhibits lipid A biosynthesis, and significantly increases cell permeability in A. baumannii[2].
In Vivo	PF-5081090 (8.75, 75, 300 mg/kg; s.c.; single dose) exhibits a exposure increasing in linear manner across the dose range in mice, with area under the concentration-time curve (AUC) and maximum concentration of drug in serum (Cmax) increasing with a proportional increase in dose[1]. PF-5081090 shows potent efficacies against sentinel strains of P. aeruginosa and K. pneumonia in CD-1 mice, with effective dose (ED50) ranging from 7.4-55.9 mg/kg (against acute septicemia model), <25 mg/kg (against pneumonia model), and 16.8 mg/kg (against neutropenic thigh model) in mice infected with P. aeruginosa PA-1950[1]. Pharmacokinetics of PF-5081090 in CD-1 micea[1] Dose (mg/kg) Cmax (mg/L) Tmax (h) AUC (h•mg/L) Free AUC (h•mg/L) T1/2 (h) CL (L/h/kg) Vss (L/kg) 18.75 5.02 0.25 5.09 1.58 0.6 3.79 2.20 75 15.50 0.33 17.60 5.46 0.69 4.32 3.30 300 75.40 0.33 76.30 23.70 0.68 3.92 2.53a Following single subcutaneous doses.
References	[1]. Tomaras AP, et al. LpxC inhibitors as new antibacterial agents and tools for studying regulation of lipid A biosynthesis in Gram-negative pathogens. mBio. 2014 Sep 30;5(5):e01551-14. [2]. García-Quintanilla M, et al. Inhibition of LpxC Increases Antibiotic Susceptibility in Acinetobacter baumannii. Antimicrob Agents Chemother. 2016 Jul 22;60(8):5076-9.

Molecular Formula	C₁₈H₂₁FN₂O₆S
Molecular Weight	412.43300
Exact Mass	412.11000
PSA	126.57000
LogP	3.28290

RIDADR	NONH for all modes of transport

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