Welch W M, Harbert C A, Sarges R, Weissman A, Koe B K
J Med Chem. 1986 Oct;29(10):2108-11. doi: 10.1021/jm00160a053.
Substitution of position 2 of the 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole nucleus with omega-carboxamidoalkyl substituents leads to compounds with exceedingly potent neuroleptic activity in in vitro and in vivo models. Although duration of activity is not as long as that of the analogous 4-hydroxy-4-(4-fluorophenyl)butyl derivatives reported previously, the absolute potency in vivo is greater. The ability of these compounds to bind with great affinity to dopamine (DA) receptors further defines the nature of the DA receptor auxiliary binding site as a hydrogen-bond donating site in addition to or instead of a lipophilic site as has been previously proposed.
在4a,9b-反式-2,3,4,4a,5,9b-六氢-1H-吡啶并[4,3-b]吲哚核的2位用ω-羧酰胺基烷基取代基进行取代，可得到在体外和体内模型中具有极强抗精神病活性的化合物。尽管活性持续时间不如先前报道的类似4-羟基-4-(4-氟苯基)丁基衍生物长，但体内绝对效力更高。这些化合物与多巴胺（DA）受体具有高亲和力结合的能力，进一步确定了DA受体辅助结合位点的性质，即除了先前提出的亲脂性位点之外或取而代之的是一个氢键供体位点。
