Structural modification patterns from agonists to antagonists and their application to drug design — A new serotonin (5-HT3) antagonist series

The development of a knowledge base for basic active structures: an example case of dopamine agonists

“…BAS extraction from dopamine D1 agonists is provided as an example, and the resulting BASs from D1, D2, and Dauto agonists are described using template structures. The results provide a more detailed understanding of active structures compared to previous studies [2,13]. …”

“…One typical approach is employed in the commercial system LHASA [1], which compiles empirical knowledge with QSAR results in toxicology and uses an expert system framework to predict the toxic effects of a new compound. Characteristic substructures of dopamine agonists have been extracted based on purely empirical considerations [2]. The present study was performed to elaborate on the characteristic substructures using dopamine agonists as an example.…”

Serotonin 5-HT3 and 5-HT4 receptor antagonists

“…11) for which functional data has been quoted includes KB-6933. 49,113 Using an interesting approach of converting agonists to antagonists using a 2-D representation of molecules on a polyhexagon matrix, piperazinylbenzimidazoles, originally investigated as H 1 antagonists and bearing remarkable similarity to quipazine, were identified as possible prototype structures. SAR showed groups larger than N-methyl on the piperazine were not tolerated and 1-substitution on the benzimidazole was optimized with C5 alkyl side chains, smaller and larger being less potent.…”

Structural Modification From Agonists to Antagonists in the Synthesis of New 5-Hydroxytryptamine (5-HT<SUB>3</SUB>) Receptor Antagonists and Preliminary In-vitro Pharmacological Evaluation on Guinea-pig Ileum

“…To analyse the variation patterns in the structural modi®cation processes and to use common variation patterns as possible principles to synthesize new selective antagonistic drugs, the structures of agonists and their antagonists were superimposed on a twodimensional grid template composed of regular hexagons. The topological similarities and differences of substructural elements between agonists and antagonists were examined (Ohtaka & Fujita 1994).…”

“…The procedure of analyses and rules to draw the structures on this template were followed exactly as reported and the highest priority was given to positioning the cationized amino or imino nitrogens. Structures of some representative agonists and antagonists acting at the 5-HT 3 receptor placed on a hexagonal template are shown in Figures 1 and 2, respectively (Ohtaka & Fujita 1994). Ohtaka & Fujita (1994) have also proposed, based on the hexagonal template, an outline skeletal structure for the superimposition of agonists and antagonists at the 5-HT 3 receptor ( Figure 3).…”