Novel adrenoceptor antagonists with a tricyclic pyrrolodipyridazine skeleton.
A still unknown tricyclic heterocyclic system (5) was synthesized from 6-hydroxy-2-methylpyridazin-3-one and its structure identified as 2,8-dichloro-6-methylpyrrolo[1,2-b:3,4-d']dipyridazin-5(6H)- one by spectroscopic investigations. Selective condensation of 5 with 2-[4-(2-substituted-phenyl)piperazin-1-yl]ethylamine gave the 2-arylpiperazinylethylamino-8-chloro derivatives 6a-c, which were investigated in binding studies toward the three alpha1-adrenergic and 5-HT1A-serotonergic receptor subtypes. They displayed high potency on all the assays and some selectivity for alpha1a and alpha1d subtypes.
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Istituto di Chimica Farmaceutica e Tossicologica, Università di Milano, Viale Abruzzi 42, 20131 Milano, Italy.
Cignarella
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Montesano
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Leonardi
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A
Mella
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Toma
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D018674:Adrenergic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
C116994:8-chloro-2-(2-(4-(2-chlorophenyl)piperazin-1-yl)ethylamino)-6-methylpyrrolo(1,2-b 3,4-d')dipyridazin-5(6H)-one; C117048:8-chloro-2-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethylamino)-6-methylpyrrolo(1,2-b 3,4-d')dipyridazin-5(6H)-one; C117049:8-chloro-2-(2-(4-phenylpiperazin-1-yl)ethylamino)-6-methylpyrrolo(1,2-b 3,4-d')dipyridazin-5(6H)-one; D018674:Adrenergic Antagonists; D011724:Pyridazines; D011758:Pyrroles; D018340:Receptors, Adrenergic, alpha-1; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1