2. Academic Validation
  3. 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

  • J Med Chem. 2015 Mar 26;58(6):2821-33. doi: 10.1021/acs.jmedchem.5b00043.
Qinhua Huang 1,  Eugene Y Rui 1,  Morena Cobbs 1,  Dac M Dinh 1,  Hovhannes J Gukasyan 1,  Jennifer A Lafontaine 1,  Saurabh Mehta 1,  Brian D Patterson 1,  David A Rewolinski 1,  Paul F Richardson 1,  Martin P Edwards 1
Affiliations

Affiliation

  • 1 La Jolla Laboratories, Pfizer Worldwide Research and Development, 10770 Science Center Drive, San Diego, California 92121, United States.
PMID: 25728019 DOI: 10.1021/acs.jmedchem.5b00043
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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