Lead optimization of 8-(methylamino)-2-oxo-1,2-dihydroquinolines as bacterial type II topoisomerase inhibitors

In Vitro and In Vivo Activities of TP0480066, a Novel Topoisomerase Inhibitor, against Neisseria gonorrhoeae

“…We have synthesized a new class of MAOQ derivative, TP0480066. TP0480066 is a novel bacterial topoisomerase inhibitor that inhibits both bacterial DNA gyrase and topoisomerase IV (18). The present study demonstrated that TP0480066 is highly effective against N. gonorrhoeae both in vitro and in vivo.…”

“…All TP0480066-resistant isolates had an alteration in parE gene but not in gyrB, indicating the possibility that TP0480066 acts as a single target inhibitor of ParE intracellularly which could be one of the causes of the relatively higher frequency of resistance of TP0480066. The unbalanced activity of TP0480066 observed in E. coli DNA gyrase and topoisomerase IV (18) could make TP0480066 a single target inhibitor since the tested concentration of TP0480066 might not be sufficient to inhibit both enzymes in bacterial cell. Although enzyme inhibitory activity of TP0480066 against topoisomerases of N. gonorrhoeae is not tested, unbalanced activity of TP0480066 might also be observed in N. gonorrhoeae.…”

“…Antibacterials. TP0480066 was synthesized by Taisho Pharmaceutical Co., Ltd. (Saitama, Japan) as described elsewhere (18). Ciprofloxacin was purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan).…”

“…The spread of fluoroquinolone-resistant bacteria among various bacterial species is now a clinically significant problem. TP0480066, a novel 8-(methylamino)-2-oxo-1,2-dihydroquinoline (MAOQ) derivative, effectively inhibits not only DNA gyrase but also topoisomerase IV (18). We evaluated the potential of TP0480066 for use in the treatment of gonorrhea.…”

Efficient synthesis of 3‐sulfonyl‐1,2‐dihydroquinolines via tandem aza‐Michael addition/cyclizations of N‐acyl‐protected 2‐aminobenzaldehyde with vinyl sulfones

“…The 1,2-dihydroquinolines (1,2-DHQs) are an important class of compounds widely present in natural products [1,2], synthetic pharmaceutical molecules, and biologically active compounds [3][4][5][6]. 1,2-DHQs have increasingly gained special attention due to a number of pharmaceutical drugs containing a 1,2-dihydroquinoline moiety which plays a crucial role in the core pharmacophore, and structurally similar synthetic analogs also have the potential to be biologically active.…”