COMPARATIVE MOLECULAR-FIELD ANALYSIS (COMFA) ON [6]+[6] FUSED PYRAZINES WITH NEMATOCIDE PROPERTIES

Quantitative structure-activity relationship (QSAR) studies, using the Comparative Molecular Field Analysis (CoMFA), on a series of 6,7-diar ylpteridine derivatives showing nematocide properties have been carrie d out. The CoMFA. model generated in the study has been used to estima te the namatocide activity ((MIC50) of seven 6,7-diarylpteridines rela ted to those previously studied. The model is highly predictive for al l pteridine derivatives in the test set. Moreover, this model also pre dicts satisfactorily the nematocide activity of other [6]+[6] fused py razines (quinoxalines and pyridopyrazines) which were not represented in the training set. The analysis revealed the importance of steric fa ctors (64.8%) and then the electrostatic ones (35.8%). Most pteridines under study were previously synthesized and tested as nematocide agen ts. Now, the synthesis and biological evaluation of 6,7-di-(2'-thienyl )-4(3H)-thioxo-pteridine 36 are reported.