Synthetic manifestation of trinitro-pyrazolo-2H-1,2,3-triazoles (TNPT) as insensitive energetic materials.

This study showcases the design and development of a facile method for synthesizing trinitro-pyrazolo-triazole (TNPT) and its derivatives. The synthesized compounds are analysed using multinuclear NMR [1H, 13C, and 15N] and HRMS analyses. Furthermore, X-ray diffraction studies confirm the structure of some TNPT derivatives. Notably, compounds 8, 9, 11, and 12 exhibit good thermal stability with a decomposition threshold above 250 °C, and show a high level of insensitivity towards impact and friction [impact sensitivity (IS) is more than 25 J and friction sensitivity (FS) is above 180 N]. Compound 12, in particular, displays excellent performance characteristics [density 1.76 g cc-1 (at 298 K), a high detonation velocity (Dv = 8550 m s-1), and good thermal stability (Td = 280 °C), with high insensitivity towards impact and friction (IS = 35 J; FS = 180 N)]. The Hirshfeld surface analysis study provides further insight into the sensitivity of the TNPT derivatives.

Polynitro-N-aryl-C-nitro-pyrazole/imidazole Derivatives: Thermally Stable-Insensitive Energetic Materials.

A wide array of methoxy-substituted-polynitro-aryl-pyrazole/imidazoles with readily oxidizable -NH2/NO2/NHNO2/diazo functional groups is synthesized. Single crystal X-ray diffraction (XRD) analysis confirms the molecular structure of the compounds. Energetic properties of the synthesized compounds are determined by theoretical and experimental studies. Most of the compounds are thermally stable and insensitive to impact and friction. Some of the molecules possess better detonation velocity and detonation pressure over TNT.

Design, Synthesis, and Antiviral activity of 1,2,3,4-Tetrahydropyrimidine derivatives acting as novel entry inhibitors to target at "Phe43 cavity" of HIV-1 gp120.

The HIV-1 invasion is initiated with the interaction of viral glycoprotein gp120 and cellular receptor CD4. The binding mechanism reveals two major hotspots involved in gp120-CD4 interaction. The first one is a hydrophobic cavity (Phe43 cavity) on gp120 capped with phenyl ring of phe43CD4 and the second is the electrostatic interaction between positive charge of Arg59CD4 and negative charge of Asp368gp120. Targeting these hotspots, small molecules for entry inhibition and HIV-1 neutralization were designed and tested. In the process, pyrimidine derivatives were identified as potent molecules to intercept gp120-CD4 binding by targeting both the hotspots. Herein, the synthesis, characterization of 1,2,3,4-Tetrahydropyrimidine derivatives, and biological evaluation on 93IN101, a clade C virus are presented. The paper presents a novel set of entry inhibitors to target dual hotspots on gp120 to inhibit protein-protein interactions.

Design, synthesis, and evaluation of HIV-1 entry inhibitors based on broadly neutralizing antibody 447-52D and gp120 V3loop interactions.

The third variable loop region (V3 loop) on gp120 plays an important role in cellular entry of HIV-1. Its interaction with the cellular CD4 and coreceptors is an important hallmark in facilitating the bridging by gp41 and subsequent fusion of membranes for transfer of viral genetic material. Further, the virus phenotype determines the cell tropism via respective co- receptor binding. Thus, coreceptor binding motif of envelope is considered to be a potent anti-viral drug target for viral entry inhibition. However, its high variability in sequence is the major hurdle for developing inhibitors targeting the region. In this study, we have used an in silico Virtual Screening and "Fragment-based" method to design small molecules based on the gp120 V3 loop interactions with a potent broadly neutralizing human monoclonal antibody, 447-52D. From the in silico analysis a potent scaffold, 1,3,5-triazine was identified for further development. Derivatives of 1,3,5-triazine with specific functional groups were designed and synthesized keeping the interaction with co-receptor intact. Finally, preliminary evaluation of molecules for HIV-1 inhibition on two different virus strains (clade C, clade B) yielded IC50 < 5.0 µM. The approach used to design molecules based on broadly neutralizing antibody, was useful for development of target specific potent antiviral agents to prevent HIV entry. The study reported promising inhibitors that could be further developed and studied.

Lewis Acid-Driven Meyer-Schuster-Type Rearrangement of Yne-Dienone.

Developed herein is a Cu(II)-catalyzed Meyer-Schuster-type rearrangement of alkyne-tethered cyclohexadienone for the construction of m-enone-substituted phenols. The reaction involves an uncommon 5-exo-trig 1,6-enyne cyclization of alkyne-tethered-cyclohexadienone, aromatization-triggered C-O bond cleavage, and an electrocyclic 4π-ring-opening of oxetene intermediate. This atom-efficient transformation provides access to a wide range of synthetically important α-(m-substituted phenol)-α,ß-unsaturated ketones, featuring a broad scope with labile functional group tolerance. The gram-scale demonstration makes this transformation synthetically viable. The synthetic application of α,ß-unsaturated ketones is also showcased.