1994 年 42 巻 12 号 p. 2556-2564
A series of pyrimido[1, 6-α]indol-1(2H)-ones was prepared and evaluated for 5-HT3 receptor antagonist activity. The compounds in this series were regarded as bioisosters of the pyrido[1, 2-α]indol-6(7H)-ones previously reported. High potency was found for compounds having 5-methyl substituents on both the pyrimido[1, 6-α]indole ring and the imidazole ring. Optimized members of this series, 8b and (+)-26a, were potent 5-HT3 receptor antagonists as determined by measuring inhibition of the Bezold-Jarisch reflex in anesthetized rats (ED50 0.6 and 0.8 μg/kg i.v., respectively), being equipotent to or more potent than FK 1052 (1) in the previous paper and 20- to 30-fold more potent than ondansetron (2).
