Design, synthesis and activity evaluation of novel pyridinone derivatives as anti-HIV-1 dual(RT/IN) inhibitors

Three series of novel anti-immunodeficiency virus 1 （HIV-1） dual （RT/1N） inhibitors were rationally designed by introducing a functioning diketo acid （DKA） into pyridin-2-one scaffold. To efficiently analyze inhibitory activity, these compounds were screened against HIV-1 RT and IN respectively via surface plasmon resonance （SPR）, and active compounds were subsequently evaluated by enzyme assay. It was noteworthy that compound A2 exhibited moderate activity against both HIV-1 RT and IN. This result provided information for further development of pyridinone analogues as potent dual HIV-1 inhibitors.

Similar pyridinone compounds with different activities of anti-HIV-1 reverse transcriptase

Among the structurally diverse NNRTIs, pyridinone scaffolds demonstrate high potency against HIV-1 wild type and drug-resistant strains. During the optimization of our pyridinone compound 1（LAM-trans）, we found that the introduction of the N atoms in the C-4 position could dramatically improve the water solubility（7b）, whereas protonation of the piperidine N atom resulted in a decrease in its hydrophobic interaction with the binding pocket. In particular, protonation altered the orientation of the alicyclic rings in the hydrophobic pocket, thus impeding the formation of key halogen bond and eventually leading to a huge change in anti-HIV-1 RT activity. These results provided theoretical and experimental basis for the subsequent structural modification of pyridinone compounds.

Visible and near-infrared luminescence of polycatenated cationic pyridinone lanthanide networks

A series of isomorphic lanthanide coordination polymers [Ln（Ⅲ）（MBP）2（NO3）2（Br）- 2C3H60] [Ln=Eu, Tb, Er, Yb, and Gd; MBP=N,N＇-methylene-bis（pyridin-4-0ne）] featuring polycatenated sql cationic network and incorporated bromide counter ion were prepared. Their visible and near-infrared （NIR） luminescence properties were characterized by steady-state excitation and emission spectra, as well as luminescence lifetimes and quantum yields. The D2d dodecahedron coordination geometry causes visible light excitations and strongly monochromatic emissions. The external heavy-atom environment induces remarkable en- hancement on the NIR emissions. The sensitization processes are revealed by analyzing the electronic properties of MBP ligand.

Synthesis and Crystal Structure of Tris(N-p-methylphenyl-3-hydroxy-2-ethyl-4-pyridinonato)iron(III)

The complex [Fe(C14H14NO2)3]2H2O has been prepared by reaction of N-p-methylphenyl-3-hydroxy-2-ethyl-4-pyridinone with FeCl36H2O. A single-crystal X-ray study shows that the iron atoms lie in a trigonally distorted octahedral environment coordinated to the hydroxy and ketone oxygen atoms of three ligands in the mer configuration Mr=773.57(C42H46N3O8Fe). The crystal is hexagonal with space group P31c; a=15.943(2), c=17.612(4)? V=3877.0(12)?, Z=4, Dc=1.325g/cm3, m=0.445mm-1, F(000)=1634, R=0.0446, wR= 0.1154 for 3085 reflections with I >2s(I). The bond lengths from iron to oxygens are 1.980(1)?for the ketone oxygens and 2.071(1)?for the hydroxy oxygens. The molecule exhibits the expected propeller shape, and the angle of the trigonal twist is 48.37. The dihedral angles are 0.5(2)?between chelate ring plane and pyridine ring plane and 71.31(7)?between pyridine ring plane and benzene ring plane. The solvent H2O(O(3) and O(4)) molecules are linked with O(2) and O(1) by hydrogen bonds with bond lengths 2.900(1) and 2.999(1)? respectively.

Design,synthesis and anti-HIV-1 activity of 4,6-dibenzyl-2-oxo-1,2-dihydropyridine-3-carbonitrile

An effective synthesis method for preparing 4,6-disubstituted pyridinones was reported. Ethyl 3-oxo-4-phenylbutyrate was an important intermediate, by which 6-substituted pyridinones could be prepared. The decarboxylation condition was optimized for compound 4. After protected with a methoxy group, the compound was reacted with BnBr to form the target compound 11. The structures were characterized by ^1H NMR, ^13C NMR and HRMS, and its enzyme inhibition activity was also determined.

A Simple One-pot Synthesis of 3,5-Dicyano-1,2-dihydropyrid-2-ones in Aqueous Media

A simple and clean synthesis of 3,5-dicyano-1,2-dihydropyrid-2-ones by a one-pot three-component reaction of malononitrile, aromatic aldehydes and 2-cyanoacetamide or 2-cyanothioacetamide has been achieved in an aqueous solution with potassium carbonate as a base under microwave irradiation without a phase transfer reagent. This protocol has the advantages of short reaction time （5-8 min） and convenient work-up.

Pyridin-2(1H)-ones as HIV-1 NNRTIs:a combinatorial optimization strategy

With rapid spread of HIV(human immunodeficiency virus) on a global scale and increasingly severe drug-resistance of it,it is urgently necessary to develop novel effective anti-HIV drugs.Non-nucleoside reverse transcriptase inhibitor(NNRTIs)is one of the most significant antiretroviral drugs for fighting against HIV infection due to their various structures,unique mode of action,good efficacy and low toxicity.Pyridinone derivatives,a type of NNRTIs,have been reported to achieve remarkable development in the past few decades.In this review,we summarized current drug design and medicinal chemistry efforts toward the development of next-generation pyridinones as HIV-1 NNRTIs.

An efficient one-pot synthesis of thiophene-fused pyrido[3,2-a]azulenes via Gewald reaction

A simple and efficient procedure was developed for the synthesis of 11H（2H）-4-oxothiophene[3＇,4＇：6,5]pyrido[3,2-a]azulene-10-carboxylates（3） in moderate to good yields via the Gewald reaction of ethyl 1-cyanoacetyl-2-methoxyazulene-3-carboxylate（1） with carbonyl compounds（2） and elemental sulfur utilizing imidazole as catalyst.This reaction provides a new procedure for synthesis of pyridinone-fused azulenes.