title: Pyrimido[5,4-b]indole derivatives. 1. A new class of potent and selective alpha 1 adrenoceptor ligands.
abstract: A number of 3-substituted pyrimido[5,4-b]indole-2,4-diones (7-23) were evaluated for their in vitro alpha 1 adrenoceptor affinity by radioligand receptor binding assays. Some compounds bearing a (phenylpiperazinyl)alkyl side chain were potent alpha 1 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]indol e- 2,4-dione (10) (Ki = 0.21 nM). Discrete modifications in the structure resulted in higher selectivity (greater than 10,000 times) for alpha 1 than alpha 2, beta 2, and 5HT1A receptors. Some compounds also had affinity for the 5HT1A receptor. The most selective alpha 1 ligand was 3-[2-[4-(2-chlorophenyl)piperazin-1-yl]ethyl]pyrimido[5,4-b)indole - 2,4-dione (13).
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica, Universitá di Catania, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Russo
authors.forename: G
authors.initials: G
authors.lastname: Romeo
authors.forename: S
authors.initials: S
authors.lastname: Guccione
authors.forename: A
authors.initials: A
authors.lastname: De Blasi
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D011224:Prazosin / Q000037:antagonists & inhibitors / Q000378:metabolism; D011744:Pyrimidinones / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
chemical_list: D007211:Indoles; D011744:Pyrimidinones; D011942:Receptors, Adrenergic, alpha; D011224:Prazosin