Synthesis and structure–affinity relationship investigations of 5-aminomethyl and 5-carbamoyl analogues of the antipsychotic sertindole. A new class of selective α1 adrenoceptor antagonists Original Research Article

A new class of selective α1 adrenoceptor antagonists derived from the antipsychotic drug sertindole is described. The most potent and selective compound 1-(2-{4-[5-aminomethyl-1-(4-fluorophenyl)-1H-indol-3-yl]-1-piperidinyl}ethyl)-2-imidazolidinone (11) binds with 0.50 nM affinity for α1 adrenergic receptors and with more than 44 times lower affinity for dopamine D2,D3, D4 and serotonin 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptors. The molecular features providing high affinity for adrenergic α1 receptors and high selectivity towards dopamine D2 and serotonin 5-HT2A and 5-HT2C receptors are discussed.