A novel class of apical sodium--dependent bile salt transporter inhibitors: 1-(2,4-bifluorophenyl)-7-dialkylamino-1,8-naphthyridine-3-carboxamides

The apical sodium--dependent bile acid transporter (ASBT) is the main transporter to promote re-absorption of bile acids from the intestinal tract into the enterohepatic circulation. Inhibition of ASBT could increase the excretion of bile acids, thus increasing bile acid synthesis and consequently cholesterol consumption. Therefore, ASBT is an attractive target for developing new cholesterol-lowering drugs. In this report, a series of 1-(2,4-bifluorophenyl)-7-dialkylamino-1,8-naphthyridine-3-carboxamides were designed as inhibitors of ASBT. Most of them demonstrated potency against ASBT transport of bile acids. In particular, compoundwas found to have the best activity, resulting in 80.1% inhibition of ASBT at 10 μmol/L.

Synthesis, Evaluation and in silico studies of 1,8-Naphthyridine derivatives against antimicrobial activity.

In present studies a series of novel 1,8-Naphthyridine derivatives (3a-3f) have been synthesized using nalidixic acid as a starting material. The structures of the compounds were supported by FT-IR, 1H NMR and Mass spectral data. All the synthesized compounds have been evaluated in vitro for their antibacterial activities against several strains of microbes using agar dilution method. The synthesized compounds had moderate to good antibacterial activity. Molecular docking studies reveal that 1,8-Naphthyridine scaffold shared structural complimentary with DNA Gyrase B. Further, TOPKAT analysis on Ames mutagenicity model had shown that this class of compounds have least probability of showing toxicity on experimental animal models.