Structure−Activity Relationships of a Series of Novel (Piperazinylbutyl)thiazolidinone Antipsychotic Agents Related to 3-[4-[4-(6-Fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2,5,5-trimethyl-4- thiazolidinone Maleate
| Autor: | Sam Kongsamut, Deborah E. Bregna, Lisa L. Kerman, Joachim E. Roehr, ‡ and Ann T. Woods-Kettelberger, Mark R. Szewczak, Harold B. Hartman, Jurcak John G, Roy Corbett, Hrib Nicholas J, Kendra L. Burgher, Sharon H. Kafka |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Apomorphine Stereochemistry medicine.drug_class Atypical antipsychotic CHO Cells Motor Activity Binding Competitive Chemical synthesis Cell Line Structure-Activity Relationship chemistry.chemical_compound In vivo Cricetinae Dopamine receptor D2 Drug Discovery medicine Animals Humans Structure–activity relationship Spiro Compounds Rats Wistar Behavior Animal Molecular Structure Bicyclic molecule Receptors Dopamine D2 Chemistry 5-HT2 receptor Receptors Dopamine D4 Rats Thiazoles Spiperone Receptors Serotonin Lactam Thiazolidines Molecular Medicine Stereotyped Behavior Antipsychotic Agents |
| Zdroj: | Journal of Medicinal Chemistry. 39:4044-4057 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm960268u |
| Popis: | HP-236 (3-[4-[4-(6-Fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2,5,5- trimethyl-4-thiazolidinone maleate; P-9236) (54) displayed a pharmacological profile indicative of potential atypical antipsychotic activity. A series of piperazinyl butyl thiazolidinones structurally related to this compound were prepared and evaluated in vitro for dopamine D2 and serotonin 5HT2 and 5HT1A receptor affinity. The compounds were examined in vivo in animal models of potential antipsychotic activity and screened in models predictive of extrapyramidal side effect (EPS) liability. The synthesis of these compounds, details of their structure-activity relationships, and discovery of a new lead, compound 50, as well as further development of the profiles of compounds 50 and 54 are described. |
| Databáze: | OpenAIRE |
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