Synthesis and binding affinity of potential atypical antipsychotics with the tetrahydroquinazolinone motif.
Article Details
- CitationCopy to clipboard
Carro L, Ravina E, Dominguez E, Brea J, Loza MI, Masaguer CF
Synthesis and binding affinity of potential atypical antipsychotics with the tetrahydroquinazolinone motif.
Bioorg Med Chem Lett. 2009 Nov 1;19(21):6059-62. doi: 10.1016/j.bmcl.2009.09.041. Epub 2009 Sep 17.
- PubMed ID
- 19796944 [ View in PubMed]
- Abstract
A series of 8 new tetrahydroquinazolinone derivatives was synthesized and evaluated for binding affinity to D2 and 5-HT2A human receptors; in addition, some properties related to blood-brain barrier penetration were calculated. From the results of these assays, three compounds were selected for further binding tests on D1, D3, and 5-HT2C human receptors, which are thought to be involved in schizophrenia. From these data, compound 19b emerged as the most promising candidate based on its good binding affinities for D1, D2, and D3 receptors, high affinity for 5-HT2A, low affinity for 5-HT2C receptors, and a Meltzer's ratio characteristic of an atypical antipsychotic profile.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Clozapine 5-hydroxytryptamine receptor 2A Ki (nM) 9.12 N/A N/A Details Clozapine 5-hydroxytryptamine receptor 2C Ki (nM) 10.47 N/A N/A Details Clozapine Dopamine D1 receptor Ki (nM) 21.38 N/A N/A Details Clozapine Dopamine D2 receptor Ki (nM) 223.87 N/A N/A Details Clozapine Dopamine D3 receptor Ki (nM) 912.01 N/A N/A Details Haloperidol 5-hydroxytryptamine receptor 2A Ki (nM) 165.96 N/A N/A Details Haloperidol Dopamine D1 receptor Ki (nM) 6.17 N/A N/A Details Haloperidol Dopamine D2 receptor Ki (nM) 0.603 N/A N/A Details Haloperidol Dopamine D3 receptor Ki (nM) 11.48 N/A N/A Details