84163-42-8Relevant articles and documents
Revised Pharmacophore Model for 5-HT2A Receptor Antagonists Derived from the Atypical Antipsychotic Agent Risperidone
Shah, Urjita H.,Gaitonde, Supriya A.,Moreno, José L.,Glennon, Richard A.,Dukat, Ma?gorzata,González-Maeso, Javier
, p. 2318 - 2331 (2019/05/24)
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. Additionally, 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 homology 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 analogues 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.
A simple and efficient method for the synthesis of 1,2-benzisoxazoles: A series of its potent acetylcholinesterase inhibitors
Basappa,Mantelingu,Sadashiva,Rangappa
, p. 1954 - 1957 (2007/10/03)
A simple and efficient method for the synthesis of 6-fluoro-3-(4- piperidinyl)-1,2-benzisoxazole hydrochloride is achieved. This reaction involves hydroxylamine sulfate/KOH mediated, in situ generated oxime formation and its subsequent internal cyclisation followed by alkaline hydrolysis of N-protected ketone in one step. Synthesis of 1,2-benzisoxazole analogues is described and they are found to be potent acetylcholinesterase inhibitors.
Synthesis and Neuroleptic Activity of 3-(1-Substituted-4-piperidinyl)-1,2-benzisoxazoles
Strupczewski, Joseph T.,Allen, Richard C.,Gardner, Beth Ann,Schmid, Blaine L.,Stache, Ulrich,et al.
, p. 761 - 769 (2007/10/02)
The synthesis of a series of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles is described.The neuroleptic activity of the series was evaluated by utilizing the climbing mice assay and inhibition of spiroperidol binding.Structure-activity relationships were studied by variation of the substituent on the benzisoxazole ring with concomitant variation of four different 1-piperidinyl substituents.Maximum neuroleptic activity was realized when there was a 6-fluoro substituent on the benzisoxazole ring.The 1-piperidinyl substituent appeared less significant, although in most cases, the (1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)propyl group imparted maximum potency.The most potent compound in both assays was 6-fluoro-3--4-piperidinyl>-1,2-benzisoxazole (11b).
