Synthesis of 2,3,5,6-tetrahydro-3H-imidazo[2,1-b] [1,3,5]benzotriazepines and their oxidative ring contraction into 1-(4,5-dihydro-1H-imidazol-2-yl)-1H-benzimidazoles.
Syntheses of novel 5-aryl-2,3,5,6-tetrahydro-3H-imidazo[2,1-b] [1,3,5]benzotriazepine derivatives 3a-g were performed by reacting 2-(2-aminoarylimino)imidazolidines 1a-b with corresponding aryl aldehydes. The compounds 3 incorporating aminal group upon treatment with 2,3-dichloro-5,6-dicyano-1,2-benzoqinone (DDQ) underwent the oxidative ring contraction to give 1-(4,5-dihydro-1H-imidazol-2-yl)-2-aryl-benzimidazoles 4a-g. Reactions of the compounds 1a-c with carbonyldiimidazole (CDI) afforded novel 2,3,5,6-tetrahydro-1H-imidazo[2,1-b] [1,3,5]benzotriazepin-5-ones 5a-c which when heated in boiling methanol gave the corresponding 1-(4,5-dihydro-1H-imidazol-2-yl)-1,3-dihydro-2H-benzimidazol-2-ones 6a-c. Radioligand binding studies using rat central imidazoline I2 receptors and alpha2-adrenoceptors demonstrated that benzimidazoles 4a-g display a low affinity (microM) for these receptors while benzimidazol-2-ones 6a-b elicited a moderate affinity for I2 receptor with Ki values of 490 and 220 nM, respectively.
Saczewski
Franciszek
F
Department of Chemical Technology of Drugs, Medical University of Gdańsk, 80-416 Gdańsk, Poland. saczew@amg.gda.pl
Kobierska
Ewa
E
Tyacke
Robin J
RJ
Hudson
Alan L
AL
Nutt
David J
DJ
Gdaniec
Maria
M
D000818:Animals; D001667:Binding, Competitive; D018360:Crystallography, X-Ray; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D054755:Imidazoline Receptors; D010084:Oxidation-Reduction; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism*; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis* / Q000494:pharmacology
D007093:Imidazoles; D054755:Imidazoline Receptors; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D014227:Triazines