

![]() |
X-ray crystal structure, partitioning behavior, and molecular modeling study of piracetam-type nootropics: insights into the pharmacophore |
|
Authors | ![]() | |
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, Physical — Crystallography, X-Ray — Lipids/chemistry — Magnetic Resonance Spectroscopy — Models, Molecular — Molecular Conformation — Molecular Structure — Nootropic Agents/*chemistry — Physicochemical Phenomena — Piracetam/*chemistry — Solubility — Stereoisomerism — Structure-Activity Relationship | |
Identifiers | DOI: 10.1021/jm00001a022 PMID: 7837228 | |
Full text | ||
Citation (ISO format) | ALTOMARE, Cosimo et al. X-ray crystal structure, partitioning behavior, and molecular modeling study of piracetam-type nootropics: insights into the pharmacophore. In: Journal of medicinal chemistry, 1995, vol. 38, n° 1, p. 170-179. doi: 10.1021/jm00001a022 https://archive-ouverte.unige.ch/unige:10531 |