Kumar V. Srinivasan

Efficient Synthesis of Quinoxalines in the Ionic Liquid 1-n-Butylimidazolium Tetrafluoroborate ([Hbim]BF4) at Ambient Temperature

Abstract Quinoxaline derivatives have been synthesized in excellent yields using an ionic liquid (IL) (viz., 1-n-butylimidazolium tetrafluoroborate) as a reaction medium as well as promoter from various 1,2-diketones and aryl-1,2-diamines. The process is general for the synthesis of quinoxaline derivatives from aromatic as well as aliphatic-1,2-diketones. The advantages of the present method are ambient reaction temperature, simplicity of operation, high yields of products, the recyclability of the IL, and ecofriendly nature of the reaction medium.

A novel one-pot three-component synthesis of 2,4-disubstituted-3H-benzo[b][1,4]diazepines in water

A novel green and efficient one-pot three-component synthesis of 2,4-disubstituted-3 n H-benzo[ n b][1,4]diazepines in excellent isolated yields has been reported. The methodology initially involves the formation of ynones n via coupling of a wide range of acid chlorides with terminal alkynes catalysed by Pd(OAc n ) n 2 under copper-, ligand- and solvent-free conditions in just 10 min at rt followed by the Michael addition and cyclocondensation of n o-phenylenediamines added n in situ using water as a solvent at reflux temprature. In addition, the structure of the benzodiazepine was confirmed to be the diimino molecule and not the enamine by X-ray crystallographic analysis of the benzodiazepine n 4b. The methodology is suitable for the operation in combi-chem mode to generate libraries of a diverse array of benzodiazepines. The methodology has been successful in achieving the twin green chemistry objectives of a solvent and ligand free operation and the use of water as a non-hazardous, inexpensive and readily available solvent in the sequential reaction steps performed n in situ, thus combining the features of both economic and environmental advantages.

Antibacterial Activity of Synthesized 2,4,5-Trisubstituted Imidazole Derivatives

Some novel chemically synthesized 2,4,5‐trisubstituted imidazoles from aryl aldehydes and 1,2‐diketones or α‐hydroxyketone were screened against eight different human pathogenic bacteria and fungi. Seven compounds were found to be active against different bacteria. These compounds showed variation in activity and were found to be active against Gram‐positive as well as Gram‐negative bacteria. Compound 4‐(4,5‐diphenyl‐1H‐imidazol‐2‐yl)‐phenol, 3d was the only compound which showed activity against Klebsiella pneumoniae while rest of the compounds did not show significant activity against this micro‐organism. Minimum inhibitory concentrations of the compounds were in the range of 0.50 to 6.1u2003μg/mL and minimum bactericidal concentration ranges from 1.11 to 12.9u2003μg/mL. The candidature of active compounds to be an effective and novel drug was examined based on Lipinski’s rule of Five which explained ClogP, LogS, H‐bond acceptors, H‐Bond donors and rotational bonds. Compounds 3a–d and 3f satisfies Lipinski’s rule of Five and could be proposed as potent new antibacterial drugs.

Simple and Efficient One‐Pot, Three‐Component, Solvent‐Free Synthesis of β‐Enaminones via Sonogashira Coupling–Michael Addition Sequences

Abstract A simple, efficient, and environmentally friendly one‐pot, three‐component synthesis of β‐enaminones via Sonogashira coupling–Michael addition sequences under solvent‐free conditions has been reported. Also the synthesis of β‐enaminones has been achieved in high yields by the direct reaction of amines with ynones under solvent‐free conditions.

Novel Process for the Synthesis of Class I Antiarrhythmic Agent (±)-Cibenzoline and Its Analogs

Abstract Synthesis of (±)-cibenzoline and its analogs has been achieved by a simple sequence of reactions. The diaryl cyanoolefin intermediate 3 could be prepared by Knoevenagel condensation of benzophenone with ethylcyanoacetate to form the tetra-substituted olefin intermediate 2 followed by Krapcho deethoxycarbonylation or from β-hydroxynitrile intermediate 2′ followed by the elimination of hydroxyl group respectively. The 2,2-diphenylcyclopropanecarbonitrile 4 was synthesized from intermediate 3 by cyclopropanation, which was converted to (±)-2-(2,2-diphenylcyclopropyl)-2-imidazoline 5 by reaction with ethylenediamine in the presence of a catalytic amount of sulfur. Moreover, the obtained 2-imidazolines were smoothly oxidized to the corresponding imidazoles 6 in good to moderate yields.

Design, Synthesis and Evaluation of Unique 2,4,5-triaryl Imidazole Derivatives as Novel Potent Aspartic Protease Inhibitors

The 2,4,5-triaryl imidazole derivatives (API) were designed, screened and characterized kinetically & thermodynamically against Pepsin and their activity was also tested on the in silico platform. The docking studies of API with Pepsin show that these are novel and unique inhibitors of Aspartic protease. Drug like properties of these compounds were validated in silico based on Lipinskis rule of Five by calculating ClogP, LogS, H-bond acceptors, H-Bond donors, rotational bonds, PSA, PB and BBB values. The Et/Ki and Et/Km values of API show that they follow the Michaelis-Menten kinetics. The binding of inhibitors with proteases was explained by using Vant Hoff plot and thermodynamic parameters viz. free energy (ΔG), Entropy (ΔS) and Enthalpy (ΔH). The Vant Hoff analysis showed that the value of Ki decreases with increase in temperature and the binding of the inhibitor are entropically driven. API act as new potent aspartic protease inhibitors with Ki, for Pepsin, ranges from 3.7 µM to 16.7 µM. Strong hydrophobic groups at C-4 & C-5 position in API favor binding of inhibitors with Pepsin. Experiments also showed that among C-2 aryl substituted imidazole, a 4-substitution on aryl ring is preferred and less polar substituent makes the molecule more active whereas polar substituents at 2-position on C-2 aryl ring makes the molecule less active. The docking studies of API with Pepsin further intensify and validate our results.