NEW CALMODULIN-ANTAGONISTS OF THE DIPHENYLALKYLAMINE TYPE .2. QSAR INVESTIGATIONS BY MEANS OF PARTIAL LEAST-SQUARE (PLS) ANALYSIS

Quantitative structure-activity relationships for a series of 71 diphe nylalkylamines which possesses a relatively high capacity of interferi ng with calmodulin have been reported. Partial least square (PLS) anal ysis was used to obtain detailed information on structural features af fecting calmodulin antagonistic activity. Apart from lipophilicity, st ructural parameters also strongly influence the activity. Chain length , the presence and/or absence of the methyl group vicinal to the nitro gen atom, the methylation of the nitrogen atom as well as the presence of the oxygen as heteroatom in combination with benzhydryl substituti on have been indicated as the most important molecular descriptors. Th e model thus provided by PLS analysis successfully predicted the biolo gical activities of additional newly synthesized prenylamine derivativ es.