- Design, synthesis, and evaluation of NO-donor containing carbonic anhydrase inhibitors to lower intraocular pressure.
Design, synthesis, and evaluation of NO-donor containing carbonic anhydrase inhibitors to lower intraocular pressure.
Journal of medicinal chemistry (2015-03-03)
Qinhua Huang, Eugene Y Rui, Morena Cobbs, Dac M Dinh, Hovhannes J Gukasyan, Jennifer A Lafontaine, Saurabh Mehta, Brian D Patterson, David A Rewolinski, Paul F Richardson, Martin P Edwards
PMID25728019
ABSTRACT
The antiglaucoma drugs dorzolamide (1) and brinzolamide (2) lower intraocular pressure (IOP) by inhibiting the carbonic anhydrase (CA) enzyme to reduce aqueous humor production. The introduction of a nitric oxide (NO) donor into the alkyl side chain of dorzolamide (1) and brinzolamide (2) has led to the discovery of NO-dorzolamide 3a and NO-brinzolamide 4a, which could lower IOP through two mechanisms: CA inhibition to decrease aqueous humor secretion (reduce inflow) and NO release to increase aqueous humor drainage (increase outflow). Compounds 3a and 4a have shown improved efficacy of lowering IOP in both rabbits and monkeys compared to brinzolamide (2).
MATERIALS
Product Number
Brand
Product Description
Mannitol, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Tetrahydrofuran, contains 250 ppm BHT as inhibitor, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99.9%
Sigma-Aldrich
Magnesium sulfate, BioReagent, suitable for cell culture, suitable for insect cell culture