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.
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Hrib NJ, Jurcak JG, Bregna DE, Burgher KL, Hartman HB, Kafka S, Kerman LL, Kongsamut S, Roehr JE, Szewczak MR, Woods-Kettelberger AT, Corbett R
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.
J Med Chem. 1996 Sep 27;39(20):4044-57.
- PubMed ID
- 8831770 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Clozapine 5-hydroxytryptamine receptor 2A IC 50 (nM) 12 N/A N/A Details Clozapine 5-hydroxytryptamine receptor 2A Ki (nM) 5 N/A N/A Details Clozapine Dopamine D4 receptor Ki (nM) 10 N/A N/A Details Clozapine Dopamine D4 receptor IC 50 (nM) 58 N/A N/A Details Haloperidol 5-hydroxytryptamine receptor 2A IC 50 (nM) 288 N/A N/A Details Haloperidol 5-hydroxytryptamine receptor 2A Ki (nM) 108 N/A N/A Details Olanzapine 5-hydroxytryptamine receptor 2A IC 50 (nM) 9 N/A N/A Details Olanzapine 5-hydroxytryptamine receptor 2A Ki (nM) 4 N/A N/A Details Olanzapine Dopamine D4 receptor IC 50 (nM) 173 N/A N/A Details Olanzapine Dopamine D4 receptor Ki (nM) 29 N/A N/A Details