Synthesis of novel 5H-pyrimido[5,4-b]indole-(1H,3H)2,4-diones as potential ligands for the cloned α1-adrenoceptor subtypes

A new series of 3-[omega-[4-(4-substituted phenyl)piperazin-1-yl]alkyl]-5H-pyrimido[5,4-b]indole-(1H,3H)-2,4-diones (3-10 and 12-13) were synthesized from the N-(2-chloroethyl)-N '-[3-(2-ethoxycarbonyl)indolyl] urea (1) or the N-(3-chloropropyl)-N '-[3-(2-ethoxycarbonyl)indolyl] urea (2) and a number of 1-(4-substituted-phenyl)piperazines. 3-[2-[4-(4-Aminophenyl)piperazin-1-yl]ethyl]-5H-pyrimido[5,4-b]indole-(1H,3H)2,4-dione (14) was obtained by reduction of the parent nitro compound 8. The obtained 5H-pyrimido[5,4-b]indole-(1H,3H)2,4-dione derivatives were tested towards cloned alpha (1A), alpha (1B) and alpha (1D)-adrenergic receptors subtypes in binding assays. Some compounds showed good affinity and selectivity for the alpha (1D)-adrenoceptor subtype.