ISSN:
1573-904X
Keywords:
astrocytes
;
chloride
;
transport
;
quantitative structure–activity relationships (QSAR)
;
comparative molecular field analysis
;
edema
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Molecular modeling studies were carried out on a series of 1-oxoisoindolines which are pharmacologically active as inhibitors of astrocytic chloride transport. Conformational analysis revealed that the halogen substituent exerted a pronounced steric directing effect on the acid side chain. The 4-substituted analogs apparently provided for the best spatial arrangement of pharamacophoric elements of the molecules. Conventional quantitative structure-activity relationship (QSAR) studies using lipophilic and dipole moment characteristics of the molecules as physical descriptor variables in the regression equation yielded a statistically significant model. Comparative molecular field analysis (CoMFA) was utilized as a three-dimensional QSAR technique to explore changes in the steric and electrostatic fields of the molecules that can account for differences in biological activity values. A highly predictive model was attained which supported the results from the qualitative and conventional quantitative structure-activity relationship analyses. These modeling techniques represent the evolutionary process by which structure-activity methods were employed to aid in the development of novel more potent inhibitors of astrocytic chloride transport.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1018937425823
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