Novel purine conjugates with N-heterocycles: synthesis and anti-influenza activity

Chemistry of Heterocyclic Compounds - A number of novel amides were synthesized by coupling of 6-[(9H-purin-6-yl)amino]hexanoic acid to heterocyclic amines. The antiviral activity of the obtained...     

Synthesis and antiviral activity of novel imidazo[2,1-b]thiazoles coupled with morpholine and thiomorpholines

Herein described the synthesis and antiviral evaluation of a novel series of morpholine and thio-morpholine coupled imidazo[2,1-b]thiazoles. The three-step reaction sequence involving the condensation of 1,3-dichloroacetone with thiourea followed by coupling with morpholine and thiomorpholine and finally cyclization with substituted α-bromoacetophenones yielded the desired imidazothiazoles 7(a–l) . Screening of all the new compounds for their in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells, resulted in two potent analogs, 7d (IC₅₀: 1.1 μM, C₅₀: >300 μM, SI = 273) and 7e (IC₅₀: 2.0 μM, C₅₀: >300 μM, SI = 150), with a favorable toxicity profile and are the best anti-influenza hit analogs for further structural optimization.     

Highly efficient and stereoselective cycloaddition of nitrones to indolyl- and pyrrolylacrylates

The reactions of various nitrones with indolyl- and pyrrolylacrylates proceeds regioselectively with high diastereoselectivity in the case of aldonitrones, and represents an effective method for obtaining new indolyl- and pyrrolyl-substituted isoxazolidine carboxylates stabilized by weak (CH?O) and moderate (NH?N) strength intramolecular hydrogen bonding. The resulting cycloadducts exhibit promising in vitro anti-influenza activities.     

First example of the cascade acylation/IMDAV/ene reaction sequence,leading to N-arylbenzo[f]isoindole-4-carboxylic acids possessing anti-viral activity

The reaction between readily accessible N-aryl-3-phenylallylamines and maleic anhydride led to unexpected products – polysubstituted hydrogenated benzo[f]isoindole-4-carboxylic acids. This transformation proceeds through a previously unknown sequence of steps: N-acylation of the allylamine with maleic anhydride, intramolecular Diels-Alder reaction of the vinylarene in the intermediate N-maleamide, and Alder-ene reaction of the products of the previous two steps. Selected benzo[f]isoindoles displayed antiviral activity.     

Synthesis,Structure, and Anti-influenza Activity of 2-(Adamantan-1-yl)-5-aryl-1,3,4-oxadiazoles and 2-(Adamantan-1-yl)-5-aryltetrazoles

Two series of new adamantyl derivatives of polynitrogen heterocycles, 2-(adamantan-1-yl)-5-aryl- 1,3,4-oxadiazoles and 2-(adamantan-1-yl)-5-aryl-2H-tetrazoles, have been synthesized, and their structure has been determined by NMR spectroscopy, mass spectrometry, and X-ray analysis. Biological studies in vitro have revealed high inhibitory activity of some of the synthesized 2-(adamantan-1-yl)-5-aryl-2H-tetrazoles against H1N1 influenza A viruses in combination with a relatively low selectivity.     

Alkylated chitosans of low molecular weight as non-viral transfection vectors for gene therapy

Low molecular weight chitosans (5 kDa) hydrophobically modified with 3, 10, and 18 mol % of tetradecenoyl (TDC) groups have been synthesized. Their good solubility at neutral pH, their surface activity and micelle-forming properties as well as their ability to interact with negatively charged phospholipid vesicles mimicking the internal layer of cell plasma membranes, allow us to consider them as potential non-viral transfection vectors for gene therapy.     

Synthesis and anti-influenza activity of 2-cyanoethoxy and 2-(1<Emphasis Type="Italic">H</Emphasis>-tetrazol-5-yl)ethoxy derivatives of dammarane-type triterpenoids

A series of 3-(2-1Н-tetrazol-5-ylethoxy- and 2-1Н-tetrazol-5-ylethoxyimino) derivatives of dammarane triterpenoids was synthesized by azidation of 3-(2-cyanoethoxy- and 2-cyanoethoxyimino)-dammaranes. The anti-influenza activity of the prepared tetrazolyldammaranes and intermediate compounds against influenza virus А H1N1 was tested. A considerable antiviral activity was observed for 20(S)-3-(2-1Н-tetrazol-5-ylethoxyimino)-25,26,27-trinor-20,24-olidedammarane (SI 26).