Antivertigo agents. V. Quantitative structure-activity relationships of 6-(2-(4-aryl-1-piperazinyl)ethyl)-5,6,7,8-tetrahydro-1,6-naphthyridines
| Autor: | Yuhichiro Ichikawa, Takao Sakamoto, Yoshiya Kogo, Hiroshi Yamanaka, Michio Ishikawa, Chikara Komuro, Akira Shiozawa, Shuji Kurashige, Hiroshi Miyazaki |
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| Rok vydání: | 1985 |
| Předmět: |
Quantitative structure–activity relationship
Magnetic Resonance Spectroscopy Chemical Phenomena Bicyclic molecule Hydrogen bond Stereochemistry Aryl Substituent General Chemistry General Medicine Ring (chemistry) Medicinal chemistry Piperazines Chemistry Structure-Activity Relationship chemistry.chemical_compound chemistry Drug Discovery Cats Vertigo Animals Moiety Molecular orbital Naphthyridines |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 33:5332-5340 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.33.5332 |
| Popis: | The quantitative structure-activity relationships (QSAR) between the molecular structures and antivertigo activities of 6-[2-(4-aryl-1-piperazinyl) ethyl]-5, 6, 7, 8-tetrahydro-1, 6-naphthyridines were investigated. The effects of the ortho-, meta-, and para-substituents on the phenyl ring of the arylpiperazine moiety were examined by means of regression analysis using various physicochemical parameters related to these substituents. The results showed that only the parameters concerning the ortho-substituent were statistically significant. Namely, the relative activity depended on both Fortho (Swain-Lupton field effect constant of the ortho-substituent) and I (indicator variable for the presence of an ortho-alkoxy group and an ortho-dimethylamino group). Thus, regression analysis for only the ortho-substituted compounds was examined and afforded a result similar to that described above. Further, the net atomic charge calculated by the molecular orbital method besides free energy-related substituent parameters was used as electronic parameters of the ortho-substituents on the phenyl ring for this QSAR analysis. For the ortho-substituted compounds alone, the potency correlated well with the net atomic charge on the first atom of the ortho-substituent (Qortho), while the correlation for all the compounds (ortho-, meta-, and parasubstituents) was slightly lower than that for the ortho-substituted compounds alone. It was found that increase in the negative net atomic charge on the first atom of the ortho-position increased the relative activity. The correlation between Qortho and Fortho and I was examined and the role of I is discussed in connection with hydrogen bond-forming ability. The interaction between the arylpiperazine moiety in the compound and a putative receptor is discussed based on the QSAR analysis. |
| Databáze: | OpenAIRE |
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