Strupczewski J T, Allen R C, Gardner B A, Schmid B L, Stache U, Glamkowski E J, Jones M C, Ellis D B, Huger F P, Dunn R W
J Med Chem. 1985 Jun;28(6):761-9. doi: 10.1021/jm00383a012.
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).
本文描述了一系列3-(1-取代-4-哌啶基)-1,2-苯并异恶唑的合成。通过使用攀爬小鼠试验和对[3H]螺哌啶醇结合的抑制来评估该系列化合物的抗精神病活性。通过改变苯并异恶唑环上的取代基以及同时改变四种不同的1-哌啶基取代基来研究构效关系。当苯并异恶唑环上有6-氟取代基时，可实现最大抗精神病活性。1-哌啶基取代基的影响似乎较小，尽管在大多数情况下，(1,3-二氢-2-氧代-2H-苯并咪唑-1-基)丙基具有最大效力。在两种试验中最有效的化合物是6-氟-3-[1-[3-(1,3-二氢-2-氧代-2H-苯并咪唑-1-基)丙基]-4-哌啶基]-1,2-苯并异恶唑(11b)。
