Nucleophilic displacement of the chlorine atom in compound 7 by aromatic amines gave ethyl 4-(arylamino)-1-phenyl-1 H-pyrazolopyridine-5-carboxylates ( 5a-k) in yields 52-82%. The cyclization of the acrylate 8 was carried out by refluxing in phosphorus oxychloride to afford 4-chloro1-phenyl-1 H-pyrazolopyridine-5-carboxylate (7) in 75% yield. In the first step, ethyl α-carboethoxy- β-(5-pyrazolylammonium)acrylate (8) was prepared by the condensation between 5-amino-1-phenyl-1 H-pyrazole (9) and diethyl ethoxymethylenemalonate, in ethanol. In the course of our search for new 1,6-naphthyridines derivatives with potential activity against HSV-1, we have synthesized and evaluated new 3 H-benzopyrazolo-1,6-naphthyridines (1a-k) and 3 H-pyridopyrazolo-1,6-naphthyridines (2a-c) (Scheme (Scheme1 1).Ī known synthetic approach was used for preparing the 3 H-benzopyrazolo-1,6-naphthyridines (1a-k) and 3 H-pyridopyrazolo-1,6-naphthyridines (2a-c), starting from ethyl 4-chloro-1-phenyl-1 H-pyrazolopyridine-5-carboxylate (7) (Scheme (Scheme1) 1). Recently, our research group reported the synthesis, SAR studies, and evaluation anti-HSV-1 activity of 3 H-benzopyrazolo-1,6-naphthyridines derivatives I (Figure (Figure1) 1). Many routes for the syntheses of 1,6-naphthyridines derivatives have previously been reported. ġ,6-Naphthyridines are a class of heterocyclic compounds that exhibit a broad spectrum of biological activities such as inhibitor of HIV-1 integrase, HCMV, FGF receptor-1 tyrosine kinase, and the enzyme acetylcholinesterase. Several examples of non-nucleoside inhibitors have been proposed as candidate drugs for the treatment of herpes. The discovery of new non-nucleoside anti-HSV-1 agents with different mechanisms of action could offer an additional strategy against drug resistance of viruses. However, the widespread use of these compounds has been associated with the emergence of drug-resistant HSV strains. Most of clinical anti-herpes virus compounds are nucleoside analogues, such as acyclovir (ACV), which is the most common drug used on treatment of HSV infections.
HSV-1 is the primary cause of facial lesions (mouth, lips, and eyes) in humans. Herpes simplex virus type-1 (HSV-1) is a large enveloped virus containing double-stranded DNA genomes of approximately 152 kb in size.
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