Wesley Chong - Nitric oxide-donating carbonic anhydrase inhibitors for the treatment of open-angle glaucoma

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      Publication Details (including relevant citation   information):

      Steele, R. M.; Benedini, F.; Biondi, S.; Borghi, V.; Carzaniga,   L.; Impagnatiello, F.; Miglietta, D.; Chong, W. K. M.; Rajapakse,   R.; Cecchi, A.; Temperini, C.; Supuran, C. T., Nitric   oxide-donating carbonic anhydrase inhibitors for the treatment of   open-angle glaucoma. Bioorganic & Medicinal Chemistry Letters   2009, 19 (23), 6565-6570.


      Novel bi-functional compounds with a nitric oxide (NO)-releasing   moiety bound to a dorzolamide scaffold were investigated. Several   compounds were synthesized and their activity as selective   carbonic anhydrase inhibitors (CAI) evaluated in vitro on   recombinant hCA type I, II and IV enzyme isoforms where they   showed different degrees of potency and selectivity to hCA II. A   high resolution X-ray crystal structure for the CA II adduct with   8 confirmed the high affinity of this class of compounds for the   enzyme. Compounds 4, 6, and 8 showed highly potent and   efficacious NO-mediated properties as assessed by their vascular   relaxant effect on methoxamine-precontracted rabbit aortic rings.   Finally, compounds 4 and 6 exerted potent intraocular pressure   (IOP) lowering effects in vivo in normotensive rabbits thereby   anticipating their potential for the treatment of hypertensive   glaucoma.

      Address (URL): http://www.sciencedirect.com/science/article/B6TF9-4XFGJ95-6/2/ac8d71df910296a02 c68a8c26d103d78