Qian, Yuanyuan; Allegretta, Giuseppe; Janardhanan, Jeshina; Peng, Zhihong; Mahasenan, Kiran V.; Lastochkin, Elena; Gozun, Melissa Malia N.; Tejera, Sara; Schroeder, Valerie A.; Wolter, William R.; Feltzer, Rhona; Mobashery, Shahriar; Chang, Mayland published the artcile< Exploration of the Structural Space in 4(3H)-Quinazolinone Antibacterials>, Recommanded Product: Thiazole-5-carboxyaldehyde, the main research area is quinazolinone preparation antibacterial pharmacokinetic SAR staphylococcus aureus QSAR.
Herein the syntheses of 79 derivatives of the 4(3H)-quinazolinones and their structure-activity relationship (SAR) against methicillin-resistant Staphylococcus aureus (MRSA) is reported. Twenty-one analogs were further evaluated in in vitro assays. Subsequent investigation of the pharmacokinetic properties singled out compound I ((E)-3-(5-carboxy-2-fluorophenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one) for further study. The compound synergized with piperacillin-tazobactam (TZP) both in vitro and in vivo in a clin. relevant mouse model of MRSA infection. The TZP combination lacks activity against MRSA, yet it synergized with compound I to kill MRSA in a bactericidal manner. The synergy is rationalized by the ability of the quinazolinones to bind to the allosteric site of penicillin-binding protein (PBP)2a, resulting in opening of the active site, whereby the β-lactam antibiotic now is enabled to bind to the active site in its mechanism of action. The combination effectively treats MRSA infection, for which many antibiotics (including TZP) have faced clin. obsolescence.
Journal of Medicinal Chemistry published new progress about Antibacterial agents. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Recommanded Product: Thiazole-5-carboxyaldehyde.
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica