Similarities in bioanalogous structural transformation patterns among various bioactive compound series.

Abstract

Successful structural transformations of bioactive compounds into newer skeletal structures by replacing the substructure with others, the features of which are not necessarily similar to but more or less drastically varied from the original one, were proposed to be called being made "bioanalogously" instead of "bioisoterically". Precedents of the bioanalogous replacements of substructures composed of the amide, urea, and related components with others were explored. Anilides, N-phenylureas, and N-phenylcarbamates are bioanalogous as herbicides and topical antiseptics. The bioanalogy can be expanded to include substructures containing ester as well as ether components when local anesthetics are considered together. The polar hydrogen-bonding groups such as (thio)urea, cyanoguanidine, and nitroethenediamine substructures found in histamine H2-receptor antagonists are also bioanalogous in various other bioactive compound series. The open-chain amides and the corresponding "carbonylogously" ring-closured dicarboximides are bioanalogous in agrochemicals and antiandrogens as well as in CNS (central nervous system)-active agents. Very often, similarities in the substructural transformation patterns are observed in various bioanalogous series regardless of differences in the pharmacological category. The observations could be used to predict newer generation structures from an ultimate lead structure.