Rimantadine

In this work, an attempt will be made to shed light on the drug design of a seemingly unusual nucleus - adamantane. On a closer look at this structure, you can see elements of rational drug-design, although the design of drugs in this group is likely to have irrational roots of bio-screening of chemical libraries.
Thus, we want to demonstrate the layering of rational design and non-rational design in drug design, which, of course, is proof in favor of the theory of everything.
This aspect is important in the context of the fact that pharmacology, as not an exact science, does not lend itself well to thorough analysis, but the tendencies in a more universal view of its branches are clearly visible, this is not a target, but an important enough message.

The work itself is implemented in the form of a diagram, for a more visual demonstration of the simplicity and elegance of a possible explanation:

Inhibitors targeting the hepatitis C virus (HCV) encoded viroporin, p7 prevent virus release in vitro. HCV can transmit by cell-free particle infection of new target cells and via cell-to-cell dependent contact with limited exposure to the extracellular environment. The role of assembly inhibitors in preventing HCV transmission via these pathways has not been studied. We compared the efficacy of three published p7 inhibitors to inhibit cell-free and cell-to-cell transmission of two chimeric HCV strains encoding genotype 2 (GT2) or 5 (GT5) p7 using a recently developed single cycle co-culture assay. The inhibitors reduced the infectivity of extracellular GT2 and GT5 virus by 80-90% and GT2 virus cell-to-cell transmission by 50%. However, all of the p7 inhibitors had minimal effect on GT5 cell contact dependent transmission. Screening a wider panel of diverse viral genotypes demonstrated that p7 viroporin inhibitors were significantly more effective at blocking cell-free virus than ce...

Milka Milevaa,*, Vera Hadjimitovaa, Lubka Tantchevab, Trayko Traykova, Angel S. Galabovc, Varban Savovc and Stefan Ribarova a Department of Biophysics, Sofia University School of Medicine, 2 Zdrave St., 1431 Sofia. Fax:+ 359-2-517-176. E-mail: mileva@ ...

Applying ab initio calculation and molecular dynamics simulation methods, we have been calculating and predicting the essential phase transition and self-assembly of two lower diamondoids (adamantane and diamantane), three of their important derivatives (amantadine, memantine and rimantadine), and two organometallic molecules that are built by substituting one hydrogen ion with one sodium ion in both adamantane and diamantine molecules (ADM • Na and Optimized DIM • Na). To study their self-assembly and phase transition behaviors, we built seven different MD simulation systems, and each system consisting of 125 molecules. We obtained self-assembly structures and simulation trajectories for the seven molecules. Radial distribution function studies showed clear phase transitions for the seven molecules. Higher aggregation temperatures were observed for diamondoid derivatives. We also studied the density dependence of the phase transition which demonstrates that the higher the density-the higher the phase transition points.

Adamantane-based compounds have been identified to interfere with the ion-channel activity of viroporins and thereby inhibit viral infection. To better understand the difference in the inhibition mechanism of viroporins, we synthesized symmetric dimeric adamantane analogs of various alkyl-spacer lengths. Symmetric dimeric adamantane derivatives were synthesized where two amantadine or rimantadine molecules were linked by various alkyl-spacers. The inhibitory activity of the compounds was studied on two viroporins: the influenza virus M2 protein, expressed in oocytes, using the two-electrode voltage-clamp technique, and the hepatitis C virus (HCV) p7 channels for five different genotypes (1a, 1b, 2a, 3a, and 4a) expressed in HEK293 cells using whole-cell patch-clamp recording techniques. Upon testing on M2 protein, dimeric compounds showed significantly lower inhibitory activity relative to the monomeric amantadine. The lack of channel blockage of the dimeric amantadine and rimantadi...

Adamantane-based compounds have been identified to interfere with the ion-channel activity of viroporins and thereby inhibit viral infection. To better understand the difference in the inhibition mechanism of viroporins, we synthesized symmetric dimeric adamantane analogs of various alkyl-spacer lengths. Symmetric dimeric adamantane derivatives were synthesized where two amantadine or rimantadine molecules were linked by various alkyl-spacers. The inhibitory activity of the compounds was studied on two viroporins: the influenza virus M2 protein, expressed in oocytes, using the two-electrode voltage-clamp technique, and the hepatitis C virus (HCV) p7 channels for five different genotypes (1a, 1b, 2a, 3a, and 4a) expressed in HEK293 cells using whole-cell patch-clamp recording techniques. Upon testing on M2 protein, dimeric compounds showed significantly lower inhibitory activity relative to the monomeric amantadine. The lack of channel blockage of the dimeric amantadine and rimantadi...