Chiral separation of (d)- and (l)-enantiomers of doxylamine succinate in rat plasma

AbstractA selective chiral ultra fast liquid chromatography (UFLC-DAD) method was developed and validated to separate and quantify the (d)- and (l)-enantiomers of doxylamine in rat plasma. After extraction of the plasma samples with acetonitrile, the separation of doxylamine succinate enantiomers and internal standard (I.S., diphenhydramine hydrochloride) was achieved on a cellulose Tris (4-chloro,3-methylphenylcarbamate) column with a mobile phase of 20mM ammonium bicarbonate buffer–acetonitrile (65:35v/v) with 0.15% diethylamine in the buffer at a flow rate of 1.0mL/min. The diode array (DAD) detection wavelength was set at 220nm. The peaks obtained were identified as (d) and (l) by injecting the pure (d) form into the liquid chromatography and comparing the chromatograms. The effect of column oven temperature on the retention of doxylamine and mobile phase variables which have an effect on the enantiomers separation like ionic strength, type and concentration of organic modifier was studied. Linear calibration curves were obtained over the range of 100–1400ng/mL in plasma for both enantiomers (R2>0.995). The mean extraction recoveries were 94.5–104.7% of rat plasma. The mean relative standard deviation (RSD%) of accuracy and intra-day and inter-day precision for both enantiomers were ⩽10%. The method can be further applied to determine the pharmacokinetics of (d)- and (l)-enantiomers in rat plasma

Synthesis of 1,3,4-oxadiazoles as promising anticoagulant agents

A series of 1,3,4-oxadiazoles were designed and subjected to molecular docking simulation onto the enzymes vitamin K epoxide reductase (PDB: 3KP9) and factor Xa (PDB: 1NFY) to visualize their binding affinity towards the said target proteins.</p

2-Methoxy-4-[3-(3-nitrophenyl)-4,5-dihydro-1H-pyrazol-5-yl]phenol

In the title compound, C16H15N3O4, the pyrazole ring has an envelope conformation, with the C atom substituted by the 2-methoxyphenol ring as the flap. Its mean plane makes dihedral angles of 56.78 (9) and 9.7 (1)° with the 2-methoxyphenol and 3-nitrophenyl rings, respectively. The benzene rings are inclined to one another by 49.37 (8)°. In the crystal, molecules are linked by pairs of O—H...N hydrogen bonds, forming inversion dimers with an R22(16) ring motif. The dimers are linked by C—H...O hydrogen bonds, forming slabs parallel to the ac plane. There are slipped parallel π–π interactions present within the slabs, involving inversion-related 2-methoxyphenol rings [intercentroid distance = 3.729 (1) Å] and inversion-related 3-nitrophenyl rings [intercentroid distance = 3.831 (1) Å]

N′-[(1E)-4-Hydroxy-3-Methoxybenzylidene]isonicotinohydrazide Monohydrate

In the title hydrate, C\sb 14H\sb 13N\sb 3O\sb 3⋅H\sb 2O, the dihedral angle between the pyridine and benzene rings is 2.52(9)\circ. Intra\-molecular O—-H⋅sO hydrogen bonds occur. In the crystal, O—-H⋅sO, O—-H⋅sN, N—-H⋅sO and C—-H⋅sO hydrogen bonds link the components into a three-dimensional network. π—π inter\-actions are also observed

Design, synthesis and evaluation of diphenyl ether analogues as antitubercular agents

We herein report the investigation of new diphenyl ethers asMycobacterium tuberculosisenoyl-acyl carrier protein reductase (InhA) inhibitors by structure-based drug design approach.</p