Islam Ullah Khan

Facile One‐Pot Synthesis of 4‐Hydroxy‐2‐methyl‐(2H)‐1,2‐benzothiazine‐3‐sulfonic Acid 1,1‐Dioxide

Abstract We report a convenient synthesis of 4‐hydroxy‐2‐methyl‐(2H)‐1,2‐benzothiazine‐3‐sulfonic acid‐1,1‐dioxide (6a) prepared in a novel one‐pot reaction. The synthesis involves two transformations starting from 2‐methyl‐2H‐1,2‐benzothiazin‐4‐(3H)‐one 1,1‐dioxide (7) with an overall yield better than that from the stepwise process, as well as the alternate procedure starting from saccharin (1). One‐pot synthesis of an important intermediate, saccharin‐N‐methane sulfonic acid (4), is also described.

Novel synthesis of dihydropyrimidines for α-glucosidase inhibition to treat type 2 diabetes: in vitro biological evaluation and in silico docking.

A convenient and efficient new method has been established for the synthesis of dihydropyrimidines by inexpensive and non-toxic N-acetyl glycine (NAG) catalysed reaction of aromatic aldehydes with ethyl acetoacetate and urea/thiourea. This method is applicable for various substituted aldehydes as well as urea and thiourea. It has also been used to synthesize bicyclic oxygen-bridged pyrimidine derivatives (4d, 4j). The biological assay revealed that the majority of compounds synthesized displayed modest inhibitory activity against α-glucosidase at low micro-molar concentrations. Molecular docking studies were also performed on the most active compound, 4f (with IC50 value 112.21±0.97 μM), to show the enzyme - inhibitor interactions.

Synthesis of new sulfonamides as lipoxygenase inhibitors.

The present study describes a convenient method for the synthesis of new lipoxygenase inhibitors, 4-(toluene-4-sulfonylamino)-benzoic acids from p-amino benzoic acid. Reaction of p-amino benzoic acid with p-toluenesulfonyl chloride provided thirteen N- and O-alkylation products 4a-4m in moderate to good yields. Lipoxygenase inhibition of newly formed sulfonamide derivatives was investigated and some of these compounds 4m, 4g, 4e, 4f and 4j showed good lipoxygenase inhibitory activities with IC(50) values ranged between 15.8 ± 0.57 and 91.7 ± 0.61 μmol whilst all other compounds exhibited mild anti-lipoxygenase activities with IC(50) values ranged between 139.2 ± 0.75 and 232.1 ± 0.78 μmol. N-alkylated products were more active against the enzyme than O-alkylated or both N- and O-alkylated ones. All synthesized sulfonamides were recrystallized in chloroform to give these title compounds which were characterized using FTIR, (1)H NMR, (13)C NMR, elemental analysis and single crystal X-ray diffraction techniques.

SYNTHESIS OF NOVEL ANTI-BACTERIAL 2,1-BENZOTHIAZINE 2,2-DIOXIDES DERIVED FROM METHYL ANTHRANILATE

A convenient ultrasound assisted synthesis of new anti-bacterial N-benzylidene-N’-(1-methyl-2, 2-dioxo-2,3-dihydro-1H-2λ6-benzo[c][1,2]thiazin-4-ylidene)hydrazines from methyl anthranilate is reported. Methyl anthranilate was reacted with methane sulfonyl chloride, followed by N-alkylation and subsequent base catalyzed cyclization. Hydrazinolysis of the cyclized products followed by their ultrasound mediated condensations with different benzaldehydes yielded the title compounds. Some of these compounds showed good anti-bacterial activity against Pseudomonas aeruginosa, Salmonella typhimurium and Staphylococcus aureus.

Spectrophotometric Determination of Methyldopa in Pure and Pharmaceutical Preparations

Methyldopa reacts with barbituric acid to give a red colour having maximum absorbance at 540 nm. The reaction is selective for methyldopa with 0.01 mg/ml as visual limit of quantitation and provides a basis for a new spectrophotometric determination. The colour reaction obeys Beers Law from 0.1 mg to 2.5 mg/10 ml of methyldopa and the relative standard deviation is 1.1%. The quantitative assessment of tolerable amount of other drugs is also studied.

Methyl 3-hydr­oxy-4-oxo-3,4-dihydro-2H-1,2-benzothia­zine-3-carboxyl­ate 1,1-dioxide monohydrate

In the molecule of the title compound, C10H9NO6S·H2O, the benzothiazine ring adopts an envelope conformation. An intramolecular N—H⋯O hydrogen bond results in the formation of a nonplanar five-membered ring which has a twisted conformation. In the crystal structure, intermolecular N—H⋯O, O—H⋯O and C—H⋯O hydrogen bonds link the molecules to form a three-dimensional network. There is a π–π contact between the benzene rings [centroid–centroid distance = 3.972 (2) Å].

Stability indicating HPLC method for the simultaneous determination of moxifloxacin and prednisolone in pharmaceutical formulations

BackgroundA simple, specific, and fast stability indicating reverse phase liquid chromatographic method was established for instantaneous determination of moxifloxacin and prednisolone in bulk drugs and pharmaceutical formulations.ResultsOptimum chromatographic separations among the moxifloxacin, prednisolone and stress-induced degradation products were achieved within 10 minutes by use of BDS Hypersil C8 column (250 X 4.6 mm, 5 μm) as stationary phase with mobile phase consisted of a mixture of phosphate buffer (18 mM) containing 0.1% (v/v) triethylamine, at pH 2.8 (adjusted with dilute phosphoric acid) and methanol (38:62 v/v) at a flow rate of 1.5 mL min-1. Detection was performed at 254 nm using diode array detector. The method was validated in accordance with ICH guidelines. Response was a linear function of concentrations over the range of 20–80 μg mL-1 for moxifloxacin (r2 ≥ 0.998) and 40–160 μg mL-1 for prednisolone (r2 ≥ 0.998). The method was resulted in good separation of both the analytes and degradation products with acceptable tailing and resolution. The peak purity index for both the analytes after all types of stress conditions was ≥ 0.9999 indicated a complete separation of both the analyte peaks from degradation products. The method can therefore, be regarded as stabilityindicating.ConclusionsThe developed method can be applied successfully for simultaneous determination of moxifloxacin and prednisolone in pharmaceutical formulations and their stability studies.

SIMULTANEOUS QUANTITATION OF OLMESARTAN MEDOXOMIL AND AMLODIPINE BESYLATE IN COMBINED TABLETS USING HPLC

ABSTRACT A simple, sensitive and isocratic reverse phase high performance liquid chromatographic (RP-HPLC) method has been developed for the simultaneous determination of olmesartan medoxomil and amlodipine in pharmaceutical tablet formulations. HPLC analysis was carried out using reverse phase isocratic elution with a C18 column and a mobile phase of 0.05 M ammonium acetate pH 6.8 and acetonitrile in the ratio of 40:60, v/v. Detection of the analytes was achieved using UV detector at 239 nm. The retention times of olmesartan medoxomil and amlodipine were 2.50 and 3.94 respectively. Linearity of the method was found to be in the concentration range of 16-112 µgml -1 for olmesartan medoximil and 4-28 µgml for amlodipine. The correlation coefficient value was greater than 0.9999 for both the analytes. The method is suitable for the estimation of both the components simultaneously in pharmaceutical tablet formulations. Key words: HPLC, acetonitrile, olmesartan, amlodipine e-mail: ashfaqchemist@hotmail.com

4-hydroxy-2H-1,2-benzothiazine-3-carbohydrazide 1,1-dioxide-oxalohydrazide (1:1): X-ray structure and DFT calculations

The title compound, 4-hydroxy-2H-1,2-benzothiazine-3-carbohydrazide 1,1-dioxide-oxalohydrazide (1:1), is determined using X-ray diffraction techniques and the molecular structure is also optimized at the B3LYP/6-31G(d,p) level using density functional theory (DFT). The asymmetric unit consists of four independent molecules. The oxalohydrazide molecules have the centre of symmetry at the mid-point of the central C-C bond. Each thiazine ring adopts a half-chair conformation. Intermolecular C-H...O, N-H...O and N-H...N hydrogen bonds produce R22 (10), R22 (13), R33 (12) and R33 (15) rings, which lead to one-dimensional polymeric chains. An extensive three-dimensional supramolecular network of N-H...N, N-H...O, C-H...O and O-H...O hydrogen bonds is responsible for crystal structure stabilization.

Crystallographic Studies of Dehydration Phenomenon in Methyl 3-hydroxy-2-methyl-1,1,4-trioxo-1,2,3,4-tetrahydro-1λ6-benzo[e][1,2]thiazine-3-carboxylate

Methyl 3-hydroxy-2-methyl-1,1,4-trioxo-1,2,3,4-tetrahydro-1λ6-benzo[e][1,2]thiazine-3-carboxylate was synthesized in single step through in situ bromination of methyl 2-methyl-1,1,4-trioxo-1,2,3,4-tetrahydro-1λ6-benzo[e][1,2]thiazine-3-carboxylate using dibenzoyl peroxide & N-bromosuccinamide and was crystallized in acetone-ethyl acetate mixture (1:1). However, crystallization in methanol converted the title compound to methyl 3-methoxy-2-methyl-1,1,4-trioxo-1,2,3,4-tetrahydro-1λ6-benzo[e][1,2]thiazine-3-carboxylate, an unsymmetrical ether. The titled compound C11H11NO6S (3) crystallized in nonoclinic space group P21/c whereas, the compound C12H13NO6S (4) crystallized in triclinic space group P-1. X-ray studies shows that the molecules of 1 are linked into a one-dimensional framework structure by C–H···O and O–H···O hydrogen bonds, while in 4, intermolecular C–H···O and C–H···π hydrogen bonds and a π···π interaction result in the formation of infinite chains running along the [010] and [001] directions.Graphical Abstract