Design, synthesis, and evaluation of NO-donor containing carbonic anhydrase inhibitors to lower intraocular pressure

Journal of Medicinal Chemistry
Qinhua HuangMartin P Edwards

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).

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Citations

Apr 26, 2017·Drug Metabolism Reviews·Upendra A ArgikarAndrea J Bushee
Jul 1, 2017·Expert Opinion on Drug Discovery·Ricardo A M SerafimElizabeth I Ferreira
Aug 17, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jennifer L DumouchelUpendra A Argikar
Oct 10, 2019·Expert Opinion on Therapeutic Patents·Claudiu T SupuranFabrizio Carta
Oct 27, 2020·Journal of Glaucoma·Tony RealiniMalik Y Kahook
Aug 27, 2021·The British Journal of Ophthalmology·Ari StonerBrent Siesky
Jun 3, 2020·Journal of Medicinal Chemistry·Kuei-Ju ChengJing-Ping Liou

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