SAR's of One-Ring Psychotomimetics

sony · Thu Mar 03, 2005 7:45 pm

Shulgin AT, Sargent T, Naranjo C. Structure--activity relationships of one-ring psychotomimetics. Nature. 1969 Feb 8;221(180):537-41

edit - see links below (thanks bander)

Bander · Thu Mar 03, 2005 7:55 pm

Your above links are to a webpage that displays the images. Wink

Below is the proper format with direct image links.

Note: Here is an easy pdf format for safe keeping ......java

Lief · Mon Mar 07, 2005 7:32 am

Check out this Experientia article on the relationship between fluorescence and hallucinogenic activity.

http://home.ripway.com/2003-11/39191/pdfs/Fluor.pdf

(ripway.com allows a maximum of 10MB transfer per day. If the link doesn't work, try back later)

scarmani · Mon Apr 25, 2005 11:06 pm

.
here are three journal articles

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QSAR studies on psychotomimetic phenylalkylamines
Mamta Thakur, Abhilash Thakurb and Padmakar V. Khadikarc,
Bioorganic & Medicinal Chemistry. 12, 825–831 (2004)
PDF
DOI: 10.1016/j.bmc.2003.10.027

Abstract:
Quantitative Structure–Activity Relationship (QSAR) studies on a series of psychotomimetic phenylalkylamines have been made using a combination of Minimum Topological Difference (MTD) method and topological methodology. The topological indices used being a pool of distance-based topological indices. The regression analyses have shown that excellent results are obtained in multiparametric model containing MTD parameters, topological indices in that quantum chemical parameters has to be introduced. The predictive power of the proposed model is discussed on the basis of cross-validation parameters.

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Structure-Activity Correlations for Psychotomimetics. 1. Phenylalkylamines: Electronic, Volume, and Hydrophobicity Parameters
Brian W. Clare,
J. Med. Chem. 33(2), 687-702 (1990)
PDF

Abstract:
CNDO/Z calculations have been performed on a series of alkyl, alkoxy, and alkylthio derivatives of phenethylamine and phenylisopropylamine. The results of these, of van der Waals volume calculations, and of Hansch type hydrophobicity calculations were correlated with psychotomimetic activity by chemometric methods. Eight parameters, involving seven chemical descriptors, were found to be highly significant. Directional hydrophobicity and volume effects were found, which suggests that steric and hydrophobic interactions in the neighborhood of the receptor site are important. A puzzling but strong interaction effect between meta and para substituents was noted. Electrunic terms may be explicable in terms of formation of charge-transfer complexes by accepting, rather than by donating, charge, as has been believed in the past. A charge effect indicates that a charge or dipole is influential at the binding site, or alternatively, a specific reactivity at the meta position is involved.

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Quasi-atomistic Receptor Surrogates for the 5-HT2A Receptor: A 3D-QSAR Study on Hallucinogenic Substances
Meike Schulze-Alexandru, Karl-Artur Kovar and Angelo Vedani,
Quant. Struct.-Act. Relat. 18, 548-560 (1999)
PDF

Abstract:
The 5-HT2A receptor is known to act as the biological target for a series of hallucinogenic substances including substituted phenylalkylamines, tryptamines and LSD. A prerequisite for a hallucinogenic effect is an agonistic binding mode to the high-affinity state of the receptor. Attempts to establish a quantitative structure-activity relationship for such compounds are typically based on homology models or 3D-QSAR. In this paper, we describe a surrogate for the 5-HT2A receptor derived by means of quasi-atomistic receptor modeling (software Quasar), a more recently developed 3D-QSAR technique. This approach allows for the simulation of local induced phenomena. The QSARs are established based on a family of receptor-surface models, generated by a genetic algorithm combined with cross-validation. The surrogate for the 5-HT2A receptor yielded a cross-validated q2 of 0.954 for the 23 compounds de®ning the training set. A series of 7 test compounds was then used to validate the model, resulting in a RMS deviation of 0.40 kcal/mol. The largest individual deviation was 0.61 kcal/mol, corresponding to an uncertainty of a factor 2.7 in the binding affnity. A scramble test with negative outcome demonstrates the sensitivity of the model with respect to the biological data. Subsequently, the surrogate was used to estimate the activity of a series of 53 hypothetical congeneric compounds, some of which are predicted to be close in activity to LSD.