Quantitative structure activity relationships for substituted naloxone benzoylhlydrazones. 4'-substituted naloxone benzoylhydrazones Journal Article
| Authors: | Charton, M.; Ciszewska, G. R.; Ginos, J.; Standifer, K. M.; Brooks, A. I.; Brown, G. P.; Ryan-Moro, J. P.; Pasternak, G. W. |
| Article Title: | Quantitative structure activity relationships for substituted naloxone benzoylhlydrazones. 4'-substituted naloxone benzoylhydrazones |
| Abstract: | Quantitative structure activity relationships (QSAR) were determined for the K(i) values measured for the interaction of 4'-substituted naloxone benzoylhydrazones with κ1, κ3, μ1, μ2, and δ receptors. Based on a comparison of the estimated and observed values of K(i) for two groups which were not in the data sets used to obtain the initial QSAR the latter give very satisfactory estimates for all but the δ receptor. The validity of the QSAR are further supported by a comparison of the observed and calculated orders of K(i) values for these two groups. The effects of the 4' substituent on K(i) are similar for the μ1 and μ2 receptors. No other similarities were observed. The results suggest that substituents of the type CH2Z and NHZ where Z has large values of the localized electrical effect parameter, σ1, should exhibit a ratio of K(i)(κ3) to K(i)(κ1) greater than 30. This is supported by the result for the acetylamino group. For all receptors but δ and possibly κ3 the 4' substituent seems to be binding to a hydrophobic region of the molecular framework through Van der Waals interactions. The segmental parameterization seems to be a better choice for the representation of steric effects than a monoparametric parameterization. The intermolecular force model is a useful alternative to the Hansch-Fujita model. The QSAR are reliable for all but the δ receptor where the results are very uncertain. |
| Keywords: | drug receptor binding; molecular model; quantitative structure activity relation; naloxone benzoylhydrazone; priority journal; article; 4'-substituted naloxone benzoylhydrazones; intermolecular force model; qsar; receptor molecule; receptor site; segmental method; steric effects; substituent binding effect; substituent-receptor interaction |
| Journal Title: | Quantitative Structure-Activity Relationships |
| Volume: | 17 |
| Issue: | 2 |
| ISSN: | 0931-8771 |
| Publisher: | Wiley - V C H Verlag GmbH & Co. KGaA |
| Date Published: | 1998-04-01 |
| Start Page: | 109 |
| End Page: | 121 |
| Language: | English |
| PROVIDER: | scopus |
| DOI: | 10.1002/(SICI)1521-3838(199804)17:02<109::AID-QSAR109>3.0.CO;2-1 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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