10.1016/j.bmcl.2007.11.060
The study focuses on the optimization of the heterocyclic core of quinazolinone-derived CXCR3 antagonists, which are compounds that block the CXCR3 receptor, a chemokine receptor involved in immune cell trafficking and implicated in various inflammatory and autoimmune diseases. The researchers synthesized a series of six-six and six-five fused heterocyclic CXCR3 antagonists and evaluated their activities in displacement assays and cell migration assays. They also studied the pharmacokinetic properties of several top-performing compounds. The aim was to discover compounds with increased potency and improved pharmacokinetic properties that could serve as tools to study the role of the CXCR3 receptor in vivo. The chemicals used in the study included various heterocyclic compounds such as quinoline, 1,8-naphthyridine, quinoxaline, benzoimidazole, imidazopyridine, imidazopyrimidine, and pyrozolopyridine derivatives. These chemicals were designed to replace the 8-aza-quinazolinone core of the existing CXCR3 antagonist AMG 487, with the goal of improving binding affinity to the CXCR3 receptor and potentially enhancing therapeutic efficacy in treating diseases like psoriasis, multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis.
10.1016/j.tetlet.2011.09.032
The research aims to develop an efficient synthetic route for lophocladines A and B, which are 2,7-naphthyridine derivatives with significant biological activities. These compounds have shown potential in various applications, including as NMDA receptor ligands and cytotoxic agents against cancer cells. The study employs nucleophilic substitution of 4-chloronicotinic acid with a carbanion generated from phenylacetonitrile as a key step, followed by reduction, lactamization, and oxidation to synthesize lophocladine A. Further amination leads to lophocladine B and its C1 analogues. 4-chloronicotinic acid (4) plays a crucial role as a starting material for the synthesis of lophocladines A and B. This compound is chosen due to its stability and ease of preparation, which makes it an ideal precursor for the nucleophilic substitution reaction that is central to the synthetic strategy. The synthesized compounds were evaluated for their cytotoxicity against leukemia cells, revealing that the naphthyridine C1 position significantly affects their potency. The study concludes that the developed synthetic method is efficient and can be applied to produce other C4 analogues, potentially expanding the scope of bioactive compounds for pharmaceutical applications.
10.1021/jm00395a015
The research focuses on the synthesis and evaluation of 2-oxo-1,8-naphthyridine-3-carboxylic acid derivatives for their potent gastric antisecretory properties. The primary purpose of this study was to develop therapeutic agents for the treatment of peptic ulcer disease by optimizing the activity of these naphthyridine derivatives. The researchers synthesized various derivatives and evaluated their effects on gastric acid secretion using the pyloric-ligated rat model and the Pavlov-pouch dog model. Key compounds tested included 4-amino-1-ethyl-1,2-dihydro-2-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester (35) and 1-ethyl-1,2-dihydro-7-methyl-4-(4-methyl-1-piperazinyl)-2-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester (77). The study concluded that these compounds were more potent than cimetidine in reducing gastric acid output in rats and dogs.
10.1021/jo01353a009
The study explores the synthesis of various substituted naphthyridines and biphenyls through different chemical reactions. Key chemicals involved include N-(3-amino-4-picolylidene)-p-toluidine, which serves as a precursor for multiple reactions to produce compounds like 1,7-naphthyridine-2-aldoxime, 2,9-diaza-6,8-dihydro-7,7-dimethyl-5-oxoanthracene, and 7,9-diazabenz[f]indane. These compounds are formed by reacting the precursor with different reagents such as isonitrosoacetone, dimethyldihydroresorcinol, and cyclopentanone under specific conditions like heating and refluxing. The products are characterized by their melting points, yields, and elemental analysis. In another part of the study, the reaction of various p-aroylpropionic acids with benzoyl chloride is investigated, yielding substituted phthalides in the biphenyl series. The study also delves into the infrared and ultraviolet spectral analysis of these products to understand their structural properties.
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