Synthesis and physicochemical properties of sulfamate derivatives as topical antiglaucoma agents

Y S Lo; J C Nolan; T H Maren; W J Welstead Jr; D F Gripshover; D A Shamblee

doi:10.1021/jm00104a003

Synthesis and physicochemical properties of sulfamate derivatives as topical antiglaucoma agents

J Med Chem. 1992 Dec 25;35(26):4790-4. doi: 10.1021/jm00104a003.

Authors

Y S Lo¹, J C Nolan, T H Maren, W J Welstead Jr, D F Gripshover, D A Shamblee

Affiliation

¹ A.H. Robins Company, Richmond, Virginia 23261-6609.

PMID: 1479580
DOI: 10.1021/jm00104a003

Abstract

Several imidazolylphenyl sulfamate and (imidazolylphenoxy)alkyl sulfamate derivatives were synthesized and evaluated as topically active carbonic anhydrase inhibitors. Water solubility, pKa, carbonic anhydrase inhibition, and partition coefficient for the compounds were measured. Sulfamic acid 2-[4-(1H-imidazol-1-yl)phenoxy]ethyl ester monohydrochloride (16) has the best combination of properties and showed excellent topical activity in lowering the intraocular pressure in New Zealand white rabbits.

MeSH terms

Administration, Topical
Animals
Carbonic Anhydrase Inhibitors / chemical synthesis*
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / therapeutic use
Glaucoma / drug therapy*
Imidazoles / chemical synthesis*
Imidazoles / chemistry
Imidazoles / therapeutic use
Intraocular Pressure / drug effects
Rabbits
Structure-Activity Relationship
Sulfonic Acids / chemical synthesis*
Sulfonic Acids / chemistry
Sulfonic Acids / pharmacology

Substances

Carbonic Anhydrase Inhibitors
Imidazoles
Sulfonic Acids