Computer Aided Prediction of Biological Activity Spectra: Study of Correlation between Predicted and Observed Activities for Coumarin-4-Acetic Acids.

Coumarin-4-acetic acids have been synthesized from various phenols and citric acid under Pechmann cyclisation conditions. All the compounds have been evaluated for antiinflammatory and analgesic activity in acute models. Compounds have also been evaluated for their ulcerogenic potential. Using the computer program, prediction of activity spectra for substances, prediction results and their Pharma Expert software, we have found a correlation between the observed and predicted antiinflammatory activity.

Vibrational and ab initio studies of 3-acetyl-6-bromocoumarin and 3-acetyl-6-methylcoumarin.

Infrared absorption and Raman spectra (3500-50 cm(-1)) of 3-acetyl-6-bromocoumarin and 3-acetyl-6-methylcoumarin have been measured and interpreted, aided by electronic structure calculations at RHF and B3LYP using 6-31(d, p) basis set. It has been determined that the rotation of the acetyl group with respect to the coumarin ring results in three conformers--two trans and one cis--for each molecule, with one trans conformer being the most stable in both cases. There are significant changes in the vibrational structure as characterized by positions and intensities of certain modes in going from 3-acetyl-6-bromocoumarin to 3-acetyl-6-methylcoumarin. The carbonyl stretching mode of the pyrone ring is stable in both molecules whereas the same mode in acetyl groups is not. Ring stretching vibrations are coupled to C-H in-plane bending vibrations. Down-shifting of frequencies of methyl vibrations in acetyl group occurs vis-à-vis methyl vibrations in 3-acetyl-6-methylcoumarin. A strong Raman band at 126 cm(-1) in both molecules is structure-independent non-genuine mode, correlated to lattice vibrations in the solid phase.

Vibrational spectra, normal modes, ab initio and DFT calculations for 6-Chloro- and 7-Chloro-4-bromomethylcoumarins.

Vibration spectral measurements - Infrared (4000-400 cm(-1)) and Raman (3500-50 cm(-1)) spectra - have been made for the solid samples of 6-Chloro- and 7-Chloro-4-bromomethylcoumarins. Ground electronic state energies, equilibrium geometries, harmonic vibrational spectra and normal modes have been computed using ab initio - RHF/6-31G* - and DFT - B3LYP/6-31G* levels of theory. The optimization yielded three structures for each molecule, with one being a transition state structure. Of the remaining two conformers, one belongs to C(s) symmetry and the other belongs to C(1), the latter being the most stable one. The optimized dihedral angle for -CH(2)Br group is 111 degrees in agreement with X-ray diffraction results reported for the similar molecular systems. Assignment of all the observed spectral bands has been proposed. The absorptions show band pattern revealing isomer characteristics and vibrational coupling in varying degrees; the Raman spectra show structural changes associated with the rings as well as lattice modes.

Vibrational assignments for 7-methyl-4-bromomethylcoumarin, as aided by RHF and B3LYP/6-31G* calculations.

Infrared (4000-400 cm(-1)) and Raman (3500-50 cm(-1)) spectral measurements have been made for the solid sample of 7-methyl-4-bromomethylcoumarin. Electronic structure calculations at RHF/6-31G* and B3LYP/6-31G* levels of theory have been performed, giving equilibrium geometries, harmonic vibrational spectra and normal modes. Different orientations of bromomethyl group have yielded only two conformers, of which the most stable one lying lower from the other conformer by approximately 7.99 kJ/mol, is non-planar with no symmetry. A complete assignment of the vibrational modes, aided by the calculations, has been proposed. Coupled vibrations are manifest in many modes. Some spectral features, compared to 6-methyl-4-bromomethylcoumarin, show changes across both IR and Raman spectra, involving mainly skeletal vibrations, and to a lesser degree, methyl and bromomethyl vibrations. Low-frequency vibrations below 150 cm(-1) are assigned to lattice modes.

Synthesis and anti-inflammatory evaluation of methylene bridged benzofuranyl imidazo[2,1-b][1,3,4]thiadiazoles.

A series of 6-substituted and 5,6-disubstituted 2-(6-methyl-benzofuran-3-ylmethyl)-imidazo[2,1-b][1,3,4]thiadiazoles have been synthesized. The new compounds have been tested for their in vivo analgesic, anti-inflammatory activities. Qualitative SAR studies indicate that the chloro substitution in the imidazole ring and introduction of formyl group at C-5 position of the imidazole ring increased the anti-inflammatory and analgesic activity. All the newly synthesized compounds have been characterized by spectral data and ORTEP diagram of one of the intermediates 6-(4-chlorophenyl)-2-(6-methyl-benzofuran-3-ylmethyl)-5-morpholin-4-ylmethyl imidazo[2,1-b][1,3,4]thiadiazole is reported herein.

Vibrational assignments and electronic structure calculations for 3-acetylcoumarin.

Laser Raman (3500-50 cm(-1)) and IR (4000-400 cm(-1)) spectral measurements have been made on the laboratory prepared solid 3-acetylcoumarin. Molecular electronic energy, equilibrium geometrical structure and harmonic vibrational spectra have been computed at the RHF/6-31G(d,p) and B3LYP/6-31G(d,p) levels of theory. A complete vibrational assignment aided by the theoretical harmonic frequency analysis has been proposed. The B3LYP/6-31G(d,p) geometrical parameters, and frequencies of the C=O in the pyrone and acetyl group are in good agreement with experiment. The difference in the frequencies due to the two carbonyl groups, 50 cm(-1), which is attributed to the conjugation effect, is accounted for by the B3LYP to be 56cm(-1).

Fourier transform-infrared and Raman spectra, ab initio calculations and assignments for 6-methyl-4-bromomethylcoumarin.

Fourier transform-infrared (4000-400 cm-1) and Raman (3500-50 cm-1) spectral measurements have been made for 6-methyl-4-bromomethylcoumarin. Equilibrium structures, harmonic vibrational frequencies, infrared intensities, and depolarization ratios have been computed at RHF/6-31G* and B3LYP/6-31G* levels of theory. Twisting CH2Br moiety in the geometry optimization leads to the most stable conformer lacking symmetry (C1). This is reflected in the richness of bands in the experimental spectra. A complete assignments of the bands, aided by the ab initio calculations, has been proposed for the 6-methyl-4-bromomethylcoumarin. Due to lack of symmetry, several normal vibrations have been found to be mixed ones.