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

Article Details

Citation

Copy to clipboard

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

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

J Med Chem. 1996 Aug 30;39(18):3533-8.

PubMed ID

8784451 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Apraclonidine	Alpha-2A adrenergic receptor	Ki (nM)	2.9	N/A	N/A	Details
Clonidine	Alpha-2A adrenergic receptor	Ki (nM)	3.8	N/A	N/A	Details
Clonidine	Alpha-2C adrenergic receptor	Ki (nM)	30	N/A	N/A	Details