Document Report Card

ID: ALA1129794

Journal: J Med Chem

Title: Synthesis and evaluation of 2-[(5-methylbenz-1-ox-4-azin-6-yl)imino]imidazoline, a potent, peripherally acting alpha 2 adrenoceptor agonist.

Authors: Munk SA, Harcourt D, Ambrus G, Denys L, Gluchowski C, Burke JA, Kharlamb AB, Manlapaz CA, Padillo EU, Runde E, Williams L, Wheeler LA, Garst ME.

Abstract: We have synthesized 2-[(5-methylbenz-1-ox-4-azin-6-yl)imidazoline, 3, a potent, peripherally acting alpha 2 adrenoceptor agonist. The agent is conveniently prepared in five steps from 2-amino-m-cresol. The agent has demonstrated good selectivity for alpha 2 adrenoceptors in binding and functional studies. When applied topically to eyes, the agent is efficacious for the reduction of intraocular pressure. The agent does not penetrate the blood-brain barrier and, as a consequence, does not lower blood pressure or induce sedation when administered topically or intravenously. We have determined the pKa and log P in water versus both octanol and dodecane of 3 and a set of related agents. The best physical parameter to explain its lack of central nervous system penetration appears to be log P measured in octanol versus water.

CiteXplore: 8784451

DOI: 10.1021/jm960359r