Hitendra S. Joshi

Multi-component synthesis of dihydropyrimidines by iodine catalyst at ambient temperature and in-vitro antimycobacterial activity.

An efficient and simple three‐component domino synthesis of some new dihydropyrimidines (DHPMs) from aromatic aldehydes, 1,3‐dicarbonyl compounds and N‐(3‐chloro‐4‐fluorophenyl)urea using molecular iodine as catalyst is described. The 1‐substituted dihydropyrimidines were isolated in good to excellent yields (78‐90%) within a short reaction time (4‐6 h) at ambient temperature. The biological evaluation revealed that the newly synthesized compounds (4a‐i and 5a‐i) exhibited moderate antimycobacterial activity against Mycobacterium tuberculosis H37 RV.

Development and validation of a stability-indicating HPLC assay method for simultaneous determination of spironolactone and furosemide in tablet formulation.

The objective of the current study was to develop and validate a simple, precise and accurate isocratic stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) assay method for the determination of spironolactone and furosemide in solid pharmaceutical dosage forms. Isocratic RP-HPLC separation was achieved on an SGE 150 × 4.6 mm SS Wakosil II 5C8RS 5-μm column using a mobile phase of acetonitrile-ammonium acetate buffer (50:50, v/v) at a flow rate of 1.0 mL/min. The detection was carried out at 254 nm using a photodiode array detector. The drug was subject to oxidation, hydrolysis, photolysis and heat to apply stress conditions. The method was validated for specificity, linearity, precision, accuracy, robustness and solution stability. The method was found to be linear in the drug concentration range of 40-160 µg/mL with correlation coefficients of 0.9977 and 0.9953 for spironolactone and furosemide, respectively. The precision (relative standard deviation; RSD) among a six-sample preparation was 0.87% and 1.1% for spironolactone and furosemide, respectively. Repeatability and intermediate precision (RSD) among a six-sample preparation were 0.46% and 0.20% for spironolactone and furosemide, respectively. The accuracy (recovery) was between 98.05 and 100.17% and 99.07 and 100.58% for spironolactone and furosemide, respectively. Degradation products produced as a result of stress studies did not interfere with the detection of spironolactone and furosemide; therefore, the assay can be considered to be stability-indicating.

Development and Validation of RP-HPLC Method for Azilsartan Medoxomil Potassium Quantitation in Human Plasma by Solid Phase Extraction Procedure

Simple and rapid reverse phase high-performance liquid chromatography (RP-HPLC) method was developed and validated using solid phase extraction (SPE) technique for the determination of Azilsartan Medoxomil Potassium (AMP) in human plasma; detection was carried out by photo diode array detector. Chromatographic separation of the analyte AMP was achieved within 7.5 min by Waters symmetry C18 (4.6 × 250 mm, 5 µm) column, mobile phase was 25 mM ammonium acetate buffer (pH 5.5): acetonitrile 55 : 45 v/v, flow rate was 1.0 mL/min, and the detection was carried out at 254 nm. Calibration curve was linear (r2 > 0.9985) in the range of 1.0–9.0 µg/mL, limit of detection (LOD) and limit of quantitation (LOQ) were 0.150 µg/mL and 0.400 µg/mL, respectively, and intra- and interday deviations were between 1.53–8.41% and 1.78–4.59%, respectively. The overall mean recovery of AMP was 92.35%. No any endogenous constituents were found to interfere at retention time of the analyte. This new RP-HPLC method was successfully validated and may be applied to conduct bioavailability and bioequivalence studies of AMP.

Synthesis of Some New 1,2,3,4-Tetrahydropyrimidine-2- thiones and Their Thiazolo[3,2-a]pyrimidine Derivatives as Potential Biological Agents

Some new N-(4-chlorophenyl)-6-methyl-4-aryl-2-thioxo-1,2,3,4-tetrahydro pyrimidine-5-carboxamide 4(a–h) were synthesized by the reaction of N-(4-chlorophenyl)-3-oxobutanamide, thiourea and different aromatic aldehydes. The synthesis of N-(4-chlorophenyl)-7-methyl-5-aryl-2,3-dihydro-5H-thiazolol[3,2-a]pyrimidine-6-carboxamide 5(a–h) was accomplished by cyclocondensation of 1,2,3,4-tetrahydropyrimidine-2-thiones 4(a–h) and 1,2-dibromoethane. The structures of these compounds have been proved by IR, 1H-NMR, and Mass spectral studies. Synthesized compounds 4(a–h) and 5(a–h) were evaluated for their antimicrobial activities. Some of the compounds exhibited significant inhibition on bacterial and fungal growth as compared to standard drugs.

Development and validation of a stability indicating method for the enantioselective estimation of omeprazole enantiomers in the enteric-coated formulations by high-performance liquid chromatography

Omeprazole is widely prescribed in the form of enteric-coated formulations, due to the rapid degradation of the drug in the acidic condition of the stomach. In the current article, we are reporting the development and complete validation of a stability indicating chiral high-performance liquid chromatography (HPLC) method for the enantioselective analysis of omeprazole in the enteric-coated formulations. A precise and sensitive enantiomeric separation of omeprazole was obtained on Chiralcel OD-H analytical column (250mm × 4.6 mm, 5μm particle size) using normal phase chromatography. The analysis was performed under UV detection at 301nm wavelength. During method development, the addition of methanol to the mobile phase helped in getting the sharp peaks. The developed method showed linear response over a wide concentration range of 0.39-800μg/ml and the regression coefficients value (r2) was obtained more than 0.999 for (S)- and (R)-omeprazole. The lower limit of detection (LLOD) and lower limit of quantification (LLOQ) for (R)-omeprazole were found to be 0.39 and 0.78 μg/ml, respectively for 5 μl injection volume. The percentage recovery of (R)-omeprazole ranged from 93.5 to 104 in spiked formulation samples and omeprazole sample solution and mobile phase were found to be stable for at least 24 h at room temperature. The proposed method was found to be suitable and accurate for the quantitative determination of undesired enantiomer in the enteric-coated omeprazole formulations.

Synthesis of Some New Pyrazolo[3,4-d]pyrimidines and Thiazolo [4,5-d]pyrimidines and Evaluation of Their Antimicrobial Activities

The desired fused ring system 3-isopropyl-4-aryl-1,4,5,7-tetrahydro-pyrazolo[3,4-d]pyrimidine-6-thiones 4a–d were synthesized by the reaction of 5-isopropyl-2,4-dihydro-3-pyrazolone 1, thiourea and different aromatic aldehydes, while 7-aryl-5-thioxo-4,5,6,7-tetrahydro-3H-thiazolo[4,5-d]pyrimidin-2-ones 7a–d were synthesized by using 2,4-thiazolidine 5 instead of 5-isopropyl-2,4-dihydro-3-pyrazolone 1. The structure of the compounds was assigned on the basis of elemental analysis, IR, 1H-NMR, and mass spectroscopy. The antibacterial activity of the newly synthesized compounds were tested against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 1539, and their antifungal activity against Candida albicans ATCC 10231 were tested using the disk diffusion method. Compounds 4b, 4c, 4d, 7c and 7d were found to be active against S. aureus ATCC 6538 (MIC: 185; 78; 156; 78; and 102 μ g/Ml, respectively) and compounds 4d and 7d against C. albicans ATCC 10231 (MIC: 312.5 μ g/mL). The minimum inhibitory concentration of these compounds was determined using the micro dilution method.

Chromatographic separation and spectroscopic characterization of the e/z isomers of acrivastine

A reverse phase high performance liquid chromatography (HPLC) method has been developed for the separation of two geometric isomers of Acrivastine using crude reaction mixture. The resolution between two isomers was found more than 2.9. The geometric isomers have been isolated by preparative HPLC and characterized by spectroscopic techniques, such as NMR, infrared, and MS. The developed method has been validated for the determination of Z-isomer in Acrivastine. The limit of detection and limit of quantification of the Z-isomer were 0.05 and 0.2 μg/ml, respectively. The developed method is precise, linear, accurate, rugged and robust for its intended use.

(E)-3-(Furan-2-yl)-1-(4-meth­oxy­phen­yl)prop-2-en-1-one

In the title molecule, C14H12O3, the prop-2-en-1-one unit forms dihedral angles of 12.96 (5) and 7.89 (7)° with the 4-methoxyphenyl group and the furan ring, respectively. The furan and benzene rings form a dihedral angle of 8.56 (5)°. In the crystal, C—H⋯π and π–π interactions are observed between the benzene and heterocyclic rings [centroid–centroid distance = 3.760 (1) Å].

Diisopropyl 1-(4-meth­oxy­phen­yl)-2,6-dimethyl-4-(3-nitro­phen­yl)-1,4-dihydro­pyridine-3,5-dicarboxyl­ate

In the title compound, C28H32N2O7, the 1,4-dihydropyridine ring adopts a flattened boat conformation. The two benzene rings are approximately perpendicular to the dihydropyridine ring, forming dihedral angles of 84.29 (9) and 82.96 (9)° with the mean plane of the 1,4-dihydropyridine unit, whereas the ester groups are only slightly twisted relative to this plane, with dihedral angles of 10.6 (1) and 9.0 (1)°.

An Efficient and Facile Synthesis of 1,2,4-Aryl Triazoles and 4-Thiazolidinones Bearing 6-Fluorochroman Nucleus

A new generation of chroman bearing heterocyclic five membered ring such as 1,2,4-triazoles and thiazolidinones was designed and synthesized. New chroman based nucleus 5-(6-fluorochroman-2-yl)-4-aryl-4H-1,2,4-triazole-3-thiol and 6-fluorochroman-N-(4-oxo-2-arylthiazolidinin-3-yl) chroman-2-carboxamides were synthesized. Aryl triazole compounds 4a–4j were synthesized from 6-fluorochroman-2-carbohydrazide 2 on reaction with base in methanol and CS2 followed by reaction with substituted aniline. Thiazolidinone compounds 5a–5j were synthesized from 6-fluorochroman-2-carbohydrazide 2 on reaction with substituted aryl aldehyde and thioglycolic acid.