Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists.
A series of 2-(arylamino)imidazoles was synthesized and evaluated for activity at alpha 1- and alpha 2-adrenoceptors. This class of agents has been shown to have potent and selective agonist activity at the alpha 2-adrenoceptors. The most potent member of this class, 2-[(5-methyl-1,4-benzodioxan-6yl)amino]imidazole, proved efficacious for the reduction of intraocular pressure upon topical administration and for the reduction of blood pressure upon intravenous administration. During the course of our studies, we developed a new reagent that allowed rapid assembly of the target compounds. This reagent, N-(2,2-diethoxyethyl)carbodiimide, was convenient to prepare and was stable under low-temperature storage conditions.
Munk
S A
SA
Allergan Pharmaceuticals, Irvine, California 92612, USA.
Harcourt
D A
DA
Arasasingham
P N
PN
Burke
J A
JA
Kharlamb
A B
AB
Manlapaz
C A
CA
Padillo
E U
EU
Roberts
D
D
Runde
E
E
Williams
L
L
Wheeler
L A
LA
Garst
M E
ME
D058647:Adrenergic alpha-2 Receptor Agonists; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D000068438:Brimonidine Tartrate; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects; D008252:Macaca fascicularis; D011810:Quinoxalines / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits
D058647:Adrenergic alpha-2 Receptor Agonists; D007093:Imidazoles; D011810:Quinoxalines; D000068438:Brimonidine Tartrate