New furoxan derivatives for the treatment of ocular hypertension

Bioorg Med Chem Lett. 2017 Feb 1;27(3):479-483. doi: 10.1016/j.bmcl.2016.12.041. Epub 2016 Dec 18.

Abstract

A small series of water-soluble NO-donor furoxans bearing a basic center at the 4-position, having a wide lipophilic-hydrophilic balance range, and endowed with different NO-release capacities, were synthesized and characterized. Selected members were studied for their IOP-lowering activity in the transient ocular hypertensive rabbit model at 1% dose. The most effective IOP-lowering products were compounds 3 and 7, whose activity 60min after administration was similar to that of Timolol. Notably, 7 was characterized by a long-lasting action. The IOP-lowering activity in this series of products appeared to be modulated by the lipophilic-hydrophilic balance rather than by the NO-donor capacity.

Keywords: Furoxan; Glaucoma; Nitric oxide; Ocular hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / chemistry
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Disease Models, Animal
  • Glaucoma / drug therapy
  • Intraocular Pressure / drug effects
  • Nitric Oxide / metabolism
  • Ocular Hypertension / drug therapy
  • Ocular Hypertension / pathology
  • Oxadiazoles / chemistry*
  • Oxadiazoles / pharmacology
  • Oxadiazoles / therapeutic use
  • Rabbits
  • Solubility
  • Timolol / pharmacology
  • Timolol / therapeutic use

Substances

  • Antihypertensive Agents
  • Oxadiazoles
  • furoxans
  • Nitric Oxide
  • Timolol