Pyrimidoindole Derivatives. 1. A New Class of Potent and Selective α1 Adrenoceptor Ligands

Article abstract of DOI:10.1021/jm00110a014

A number of 3-substituted pyrimido<5,4-b>indole-2,4-diones (7-23) were evaluated for their in vitro α₁ adrenoceptor affinity by radioligand receptor binding assays.Some compounds bearing a (phenylpiperazinyl(alkyl side chain were potent α₁ adrenoceptor ligands.The most active derivative in displacement of <3H>prazosin from rat cortical membranes was 3-<2-<4-(2-methoxyphenyl)piperazin-1-yl>ethyl>pyrimido<5,4-b>indole-2,4-dione (10) (K_i = 0.21 nM).Discrete modifications in the structure resulted in higher selectivity (> 10000 times) for α₁ than α₂, β₂, and 5HT1A receptors.Some compounds also had affinity for the 5HT1A receptor.The most selective α₁ ligand was 3-<2-<4-(2-chlorophenyl)piperazin-1-yl>ethyl>pyrimido<5,4-b>indole-2,4-dione (13).