Synthesis and neuroleptic activity of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles

Abstract

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 [3H]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-[1-[3-(1,3-dihydro-2-oxo-2H-benzimidazol-1-yl) propyl]-4-piperidinyl]-1,2-benzisoxazole (11b).

Modelling the binding step in dopamine receptor–antagonist interactions

“…The orbital form of IIIb, a 4-F-substituted derivative whose analogues are frequently found among the neuroleptics, was chosen. The two benzisoxazoles, 6-F-benzisoxazole Va, whose analogue is an active compound (ICS0 = 6.7), and 6-MeO-benzisoxazole Vb, whose analogue is practically inactive (ICS0 = 2800) (20), have similar T, values. These values are often more elevated with inactive than with active molecules (for example, T, values of Va and Vb are 0.03 and 0.07, respectively, with the active phenothiazine Ib, but 0.53 and 0.55 with the inactive phenothiazine Id).…”

Synthesis of new benzisoxazole derivatives and their antimicrobial, antioxidant and anti-inflammatory activities

“…Benzisoxazole derivatives are one of the most important heterocyclic system in the field of medicinal chemistry and associated with the wide range of biological activities such as antimicrobial [1], anticonvulsant [2,3], antitumor [4,5], antipsychotic [6][7][8], antithrombotic [9] analgesic activities [10]. They have also exhibited antiglycating [11] and cholinesteraseinhibiting properties [12][13].…”

New synthetic benzisoxazole derivatives as antimicrobial, antioxidant and anti-inflammatory agents

“…Benzisoxazole scaffold present in large number of pharmaceutical products with antimicrobial [1], anticonvulsant [2,3], antitumor [4,5], antipsychotic [6][7][8], antithrombotic [9], analgesic activities [10]. They have also exhibited antiglycating [11] and cholinesterase-inhibiting properties [12,13].…”