Sandeep Mohanty

An assembly of structurally diverse small and simple 5-aminomethylene derivatives of 2,4-thiazolidinedione and studies of their biological activity

The synthesis of a novel series of substituted 5-(aminomethylene)thiazolidine-2,4-diones was achieved using a wide range of heterocyclic models derived from eight drug-like molecules. The primary aim of this study was to combine medicinally known, biologically active molecules bearing a 2° amine functionality, such as terbinafine, fluoxetine, atomoxetine, cetirizine, risperidone, aripiprazole, ziprasidone, and clopidogrel, with a thiazolidinedione ring via an amino-methylene linker. By targeting this synergistic approach to compounds with skeletal, functional, and stereochemical diversity, we have developed a simple synthetic concept to enrich the thiazolidinedione collection with various biological activities. The biological activities of the newly synthesized 5-(aminomethylene)thiazolidine-2,4-dione derivatives were explored. All compounds were found to have antibacterial activity, with compounds bearing pyridine or piperazine moieties showing good to excellent antibacterial activity. Compounds with piperazine moieties were also found to show good antifungal activity, whereas none of the synthesized compounds showed high cytotoxic activity.

Phosphoryl Chloride Mediated Synthesis of 5-Arylidene-2,4-Thiazolidinediones Derivatives via Aromatic Bisulfite Adducts

The carbon-carbon bond formation by the condensation of bisulfite adduct of aromatic aldehydes with thiazolidine-2, 4-dione to furnish 5-arylidene-2,4-thiazolidinediones has been investigated. This novel methodology was applied to convert substituted aryl bisulfite adducts to corresponding 5-arylidene-2,4-thiazolidinediones with POCl3 in less-polar solvents such as toluene, chlorobenzene and o-xylene. 5-(4-methoxybenzylidene)thiazolidine-2,4-dione and 5-(4-ethoxybenzylidene)thiazolidine-2,4-dione were obtained in good yields.

De novo synthesis of 2,2-bis(dimethylamino)-3-alkyl or benzyl 2,3-dihydroquinazolin-4(1H)-one compounds

ABSTRACT A new versatile and efficient strategy for the synthesis of 2,2-bis(dimethylamino)-3-alkyl or benzyl 2,3-dihydroquinazoline-4(1H)-one compounds has been developed by one-pot multicomponent reaction with isatoic anhydride, amines followed by in situ-generated Vilsmeier reagent. The reaction has also been studied with different amines and solvents. GRAPHICAL ABSTRACT

Reaction pathway of POCl3-mediated Knoevenagel condensation of bisulfite adducts with 2,4-thiazolidinedione

GRAPHICAL ABSTRACT Abstract We investigated the POCl3-mediated transformation of aromatic bisulfite adducts to the corresponding 5-arylidenethiazolidine-2,4-diones. The in situ transformation of an aromatic bisulfite adduct to the parent aldehyde in a non-aqueous non-polar solvent (toluene) was demonstrated using DoE (Design of experiment), offline 1H NMR, online ReactIR, HPLC, LC-MS, and GC-MS. By means of these analytical tools, we determined, for the first time, the structure of the intermediate species (aldehyde) prior to the carbon–carbon double-bond formation. The carbon–sulfur bond undergoes a fast cleavage, immediately after the addition of POCl3, which finally affords the corresponding 5-arylidenethiazolidine-2,4-diones.

Isolation and identification of a potential unknown impurity in montelukast drug substance resulting from photolytic degradation

During related substance analysis of montelukast bulk drug, a potential unknown impurity was detected in routine reverse phase impurity profiles by high performance liquid chromatography (HPLC). This impurity was identified by LC-MS and characterized by (1H NMR, 13C NMR, gDQCOSY, gHSQC, LC/MS/MS, elemental analysis and FTIR) after isolation from montelukast drug substance exposed to sunlight. Based on spectral data, the impurity was unambiguously named as (E)-2-(2-(3-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)-3-((2-methylenebutyl)thio)propyl)phenyl)propan-2-ol. To the best of our knowledge, this impurity has not been reported elsewhere. Structural elucidation of the impurity by spectral data is discussed in detail.