Journal of Medicinal Chemistry · 1981 · 26 citations · 0 references
PharmacyMedicinal ChemistryPharmacologyDrug DesignDrug DiscoveryStructure-activity RelationshipsLead Compound DesignOncology PharmacologyPotency OptimizationQuantitative Structure-activity RelationshipsStructure-activity Relationship AnalysisChemical Synthesis Of AnaloguesCompound Potency OptimizationDrug Toxicity ModelsMedicinal HeterocyclesOptimization Of ToxicityQuantitative Structure - Property Relationship ModelingQuantitative Structure-toxicity RelationshipsTherapeutic Dose Range
A method for extracting LD50 values from antitumor test data is described. A quantitative structure--activity relationship (QSAR) for 7- and 10-substituted colchicines is presented. This correlation equation closely parallels that which had been derived earlier for potency. This result indicates that attempts to modify 7- and 10-substituted colchicines in order to decrease toxicity will likely produce a simultaneous decrease in potency. Ring A modified colchicines do not obey the potency and toxicity correlations. 4-Substituted colchicines appear promising in terms of decreased toxicity, greater ILS, and a broader therapeutic range.