Yan-Ping He

Synthesis and biological evaluation of novel dihydro-aryl/alkylsulfanyl-cyclohexylmethyl-oxopyrimidines (S-DACOs) as high active anti-HIV agents

A novel dihydro-aryl/alkylsulfanyl-cyclohexylmethyl-oxopyrimidines (S-DACOs) combinatory library was synthesized and evaluated with C8166 cells infected by the HIV-1(IIIB) in vitro, using Nevirapine (NVP) and Zidovudine (AZT) as positive control. The anti-HIV screening results revealed that C-6-cyclohexylmethyl substituted pyrimidinones possessed higher selective index than its 6-arylmethyl counterparts. Compounds 1g, 1c, 1e and 1b showed potent anti-HIV activities with EC(50) values of 0.012, 0.025, 0.088 and 0.162nM, respectively.

Design, synthesis and aromatase inhibitory activities of novel indole-imidazole derivatives

A series of novel indole-imidazole derivatives have been prepared and evaluated in vitro on the aromatase inhibitory activities. The results suggested that proton or a small electron-withdrawing group at para-position of the phenyl ring would enhance the inhibitory activities and any bulky group should be avoided in order to keep a relative small volume for this kind of molecules.

DB-02, a C-6-Cyclohexylmethyl Substituted Pyrimidinone HIV-1 Reverse Transcriptase Inhibitor with Nanomolar Activity, Displays an Improved Sensitivity against K103N or Y181C Than S-DABOs

6-(cyclohexylmethyl)-5-ethyl-2-((2-oxo-2-phenylethyl)thio)pyrimidin-4(3H)-one (DB-02) is a member of the newly reported synthetic anti-HIV-1 compounds dihydro-aryl/alkylsulfanyl-cyclohexylmethyl-oxopyrimidines, S-DACOs. In vitro anti-HIV-1 activity and resistance profile studies have suggested that DB-02 has very low cytotoxicity (CC50>1mM) to cell lines and peripheral blood mononuclear cells (PBMCs). It displays potent anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (EC50s range from 2.40 to 41.8 nM). Studies on site-directed mutagenesis, genotypic resistance profiles revealed that V106A was the major resistance contributor for the compound. Molecular docking analysis showed that DB-02 located in the hydrophobic pocket with interactions of Lys101, Val106, Leu234, His235. DB-02 also showed non-antagonistic effects to four approved antiretroviral drugs. All studies indicated that DB-02 would be a potential NNRTI with low cytotoxicity and improved activity.

6-Cyclo­hexyl­meth­yl-5-ethyl-2-[(2-oxo-2-phenyl­eth­yl)sulfan­yl]pyrimidin-4(3H)-one

In the title compound, C21H26N2O2S, the cyclohexane ring adopts a chair conformation. The angle at the methylene bridge linking the pyrimidine and cyclohexane rings is 113.41 (13)°. This is in the range considered optimal for maximum activity of non-nucleoside reverse transcriptase inhibitors. In the crystal, molecules are connected into centrosymmetric dimers via pairs of N—H⋯O hydrogen bonds.

4-Benzyl-5-ethyl-2-(2-furylcarbonylmethylsulfanyl) pyrimidin-6(1H)-one

The title compound, C19H18N2O3S, shows favourable activity against HIV-1. The phenyl ring is twisted with respect to the pyrimidine ring by 61.56 (9)degrees. Intermolecular N-H center dot center dot center dot O and C-H center dot center dot center dot O

Synthesis and biological evaluation of novel anti-hepatitis C virus (HCV) agents: 2-hydroxylphenethyl sulfanyl-oxopyrimidines

A novel series of dihydro-hydroxyl-phene-thylsulfanyl-ω-cyclohexyl/phenyl-oxopyrimidine derivatives have been synthesized and their in vitro anti-hepatitis C virus activities have been evaluated using Huh 7.5.1 cells. Some of the compounds showed moderate anti-hepatitis C virus activities, with EC50 range from 7.53 to 0.13 μM. Among all the compounds, 6-(cyclohexylmethyl)-5-ethyl-2-((2-hydroxy-2-phenylethyl)thio)-pyrimidin-4 (3H)-one (3a) had the most promising potential in inhibiting hepatitis C virus with an EC50 value of 0.13 μM and SI value of 121. It was noticed that some of these compounds are both active on hepatitis C virus and human immunodeficiency virus. In addition to experimental evaluation, structure-activity relationships and the molecular modeling analysis of these new congeners are also discussed.

N-(4-Bromo­phen­yl)-2-[(1-cyclo­hexyl­meth­yl-1H-1,2,4-triazol-3-yl)sulfanyl]­acetamide

The title compound, C17H21BrN4OS, was synthesized as a potential reverse transcriptase (RT) inhibitor of the human immunodeficiency virus type 1 (HIV-1). In the molecule, there is an N—H⋯S hydrogen bond making a five-membered ring. In the crystal, molecules are connected into centrosymmetric dimers via pairs of N—H⋯N and weak C—H⋯N hydrogen bonds. The crystal structure also features C—H⋯O interactions.

6-Cyclo-hexyl-methyl-2-cyclo-hexyl-sul-fanyl-5-isopropyl-pyrimidin-4(3H)-one.

The title compound, C20H32N2OS, was obtained during the course of our investigation on 2-alkylsulfanyl-6-benzyl-3,4-dihydropyrimidin-4(3H)-ones (S–DABOs) showing favourable anti-HIV-1 activity. Both cyclohexane rings adopt chair conformations. The angle at the methylene C atom linking the pyrimidine and cyclohexane ring is 113.7 (3)°, which is in the range considered optimal for maximum activity of non-nucleoside reverse transcriptase inhibitors. Intermolecular N—H⋯O hydrogen bonds link the molecules into dimers and stabilize the crystal structure of the compound. In addition, an intramolecular C—H⋯O hydrogen bond is observed.