Scientific Article
previous document  unige:10531  next document
add to browser collection

X-ray crystal structure, partitioning behavior, and molecular modeling study of piracetam-type nootropics: insights into the pharmacophore

Altomare, Cosimo
Cellamare, S.
Carotti, Angelo
Casini, G.
Ferappi, M.
Gavuzzo, E.
Mazza, F.
show hidden authors show all authors [1 - 10]
Published in Journal of Medicinal Chemistry. 1995, vol. 38, no. 1, p. 170-179
Abstract To detect possible molecular determinants of amnesia-reverting activity, the conformational properties of a number of rigid and flexible piracetam-type cognition enhancers have been assessed by X-ray diffraction, NMR spectroscopy, and ab initio and high-temperature-quenched molecular dynamics (QMD) calculations. The structures of the preferred conformers in solution derived from 1H-NMR spectral analysis were in good agreement with those found by QMD calculations. Interestingly, the calculation of the average molecular lipophilicity potential on the water-accessible surface of the selected conformers was helpful in interpreting the partitioning behavior observed by measuring octanol-water partition coefficients and capacity factors in reversed-phase high-performance liquid chromatography. While lipophilicity does not play a relevant role, the distance between polar groups, accounted for by the distance between carbonyl oxygens, emerges as a factor, among others, which should influence the amnesia-reversal activity of piracetam-type nootropics.
Keywords Chemistry, PhysicalCrystallography, X-RayLipids/chemistryMagnetic Resonance SpectroscopyModels, MolecularMolecular ConformationMolecular StructureNootropic Agents/*chemistryPhysicochemical PhenomenaPiracetam/*chemistrySolubilityStereoisomerismStructure-Activity Relationship
Stable URL
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Other version:
PMID: 7837228

127 hits

0 download


Deposited on : 2010-08-06

Export document
Format :
Citation style :