Shah, Urjita H.; Gaitonde, Supriya A.; Moreno, Jose L.; Glennon, Richard A.; Dukat, Malgorzata; Gonzalez-Maeso, Javier published the artcile< Revised Pharmacophore Model for 5-HT2A Receptor Antagonists Derived from the Atypical Antipsychotic Agent Risperidone>, Name: 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole, the main research area is antipsychotics schizophrenia HT2A receptor antagonist risperidone pharmacophore model; Antipsychotics; pharmacophore; risperidone; schizophrenia; serotonin 5-HT2A receptor.
Pharmacophore models for 5-HT2A receptor antagonists consist of two aromatic/hydrophobic regions at a given distance from a basic amine. We have previously shown that both aromatic/hydrophobic moieties are unnecessary for binding or antagonist action. Here, we deconstructed the 5-HT2A receptor antagonist/serotonin-dopamine antipsychotic agent risperidone into smaller structural segments that were tested for 5-HT2A receptor affinity and function. We show, again, that the entire risperidone structure is unnecessary for retention of affinity or antagonist action. Replacement of the 6-fluoro-3-(4-piperidinyl)-1,2-benz[d]isoxazole moiety by isosteric tryptamines resulted in retention of affinity and antagonist action. Addnl., 3-(4-piperidinyl)-1,2-benz[d]isoxazole (10), which represents less than half the structural features of risperidone, retains both affinity and antagonist actions. 5-HT2A receptor homol. modeling/docking studies suggest that 10 binds in a manner similar to risperidone and that there is a large cavity to accept various N4-substituted analogs of 10 such as risperidone and related agents. Alterations of this “”extended”” moiety improve receptor binding and functional potency. We propose a new risperidone-based pharmacophore for 5-HT2A receptor antagonist action.
ACS Chemical Neuroscience published new progress about 5-HT2A antagonists. 84163-77-9 belongs to class benzisoxazole, and the molecular formula is C12H13FN2O, Name: 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole.
Referemce:
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics