Deprotonation and regioselective addition of 2H-pyrazolo[3,4-c]quinolines to electrophiles

The deprotonation and regioselective reaction of 2H-pyrazolo[3,4-c]quinolines with a variety of electrophiles is described. Electrophiles include benzaldehyde, DMF, carbon dioxide, and iodine. This method provides a direct route to a class of pharmacologically interesting compounds.     

A kinetic study of product cleavage reactions from the solid phase by a biocompatible and removable cleaving reagent, HCl

TFA has been widely used as a cleaving reagent in solid-phase organic synthesis. However, it is difficult to remove from the final product, and it is toxic to various cells. To search for an alternative, we studied the kinetics of HCl cleavage reactions of 18 resin-bound compounds on various linkers. HCl is very easy to remove completely from samples, and the residual HCl does not have a toxic effect in cell assays. Most compounds studied in this work can be easily cleaved using a low concentration of HCl (0.9-2.3%) and the minimal amount of time (60-90 min). Even in the most difficult case, a moderate 8% HCl and an extended time (10-15 h) are enough to cleave the product. Therefore, our kinetic studies establish HCl as a biocompatible, removable, and effective substitute for TFA when final compounds are used for biological screening and drug discovery.     

Displacement of the indolyl sulfide linkage in the synthesis of 3-substituted indoles

The indolyl sulfide compounds ( 5,6,7,8 ) gave 3-3′-diindole methane derivatives by a double decomposition-displacement reaction. These same compounds when reacted with alkoxides yielded 3-alkoxy-methylindole derivatives ( 9-14 ).     

Color test for the detection of resin-bound aldehyde in solid-phase combinatorial synthesis

We report the development of a sensitive and specific color test for the detection of the presence of resin-bound aldehyde groups using 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (Purpald). Aldehyde resin turns dark-brown to purple after a 5 min reaction followed by a 10 min air oxidation period. Resins that possess other functional groups (i.e., ketone, ester, amide, alcohol, and carboxylic acid) do not change color under the same conditions. The detection limit is 20 micromol/g for polystyrene-based aldehyde resins.     

Designing functional aromatic multisulfonyl chloride initiators for complex organic synthesis by living radical polymerization

The similarities and differences between sulfonyl chloride and alkyl halide initiators for metal‐catalyzed living radical polymerizations are discussed. The differences in the rates of formation, reactivities, and reactions of primary radicals derived from sulfonyl halides and alkyl halides demonstrated the design principles for monosulfonyl and multisulfonyl chlorides that provided quantitative initiation and higher rates of initiation than of propagation. Multifunctional initiators with two, three, four, six, and eight sulfonyl chloride groups that produced perfect star polymers in 95% conversions were designed and synthesized on the basis of these principles. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4776–4791, 2000     

Correction to: Evaluation of background radiation level and excess lifetime cancer risk in Doon valley,Garhwal Himalaya

Journal of Radioanalytical and Nuclear Chemistry -     

Computational investigation of drug bank compounds against 3C-like protease (3CLpro) of SARS-CoV-2 using deep learning and molecular dynamics simulation

Blocking the main replicating enzyme, 3 Chymotrypsin-like protease (3CL^pro) is the most promising drug development strategy against the SARS-CoV-2 virus, responsible for the current COVID-19 pandemic. In the present work, 9101 drugs obtained from the drug bank database were screened against SARS-CoV-2 3CL^pro prosing deep learning, molecular docking, and molecular dynamics simulation techniques. In the initial stage, 500 drug-screened by deep learning regression model and subjected to molecular docking that resulted in 10 screened compounds with strong binding affinity. Further, five compounds were checked for their binding potential by analyzing molecular dynamics simulation for 100 ns at 300 K. In the final stage, two compounds {4-[(2s,4e)-2-(1,3-Benzothiazol-2-Yl)-2-(1h-1,2,3-Benzotriazol-1-Yl)-5-Phenylpent-4-Enyl]Phenyl}(Difluoro)Methylphosphonic Acid and 1-(3-(2,4-dimethylthiazol-5-yl)-4-oxo-2,4-dihydroindeno[1,2-c]pyrazol-5-yl)-3-(4-methylpiperazin-1-yl)urea were screened as potential hits by analyzing several parameters like RMSD, Rg, RMSF, MMPBSA, and SASA. Thus, our study suggests two potential drugs that can be tested in the experimental conditions to evaluate the efficacy against SARS-CoV-2. Further, such drugs could be modified to develop more potent drugs against COVID-19.

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New pyrazolyl-dibenzo[b,e][1,4]diazepinones: room temperature one-pot synthesis and biological evaluation

Molecular Diversity - Several new (5-aryloxy-pyrazolyl)- and (5-aryl/olefin-sulfanyl-pyrazolyl)-dibenzo[b,e] [1,4] diazepinone scaffolds have been synthesized, by assembling 5-substituted...