| abstract |
The present disclosure provides phosphodiesterase 5 (PDE-5) and/or phosphodiesterase 6 (PDE-6) inhibitor compounds and compositions including said compounds. In some embodiments, said compounds are nitrogen oxide (NO) donating PDE-5 and/or -6 inhibitor compounds that include a nitrogen oxide-containing donor substituent attached to a benzenesulfonamide group. The compounds can provide dual functionality for increasing protein kinase G (PKG) activity by inhibiting PDE-5 and PDE-6, and/or stimulating guanylate cyclase (sGC) via donation of nitrogen oxide (NO) from the donor substituent of the compound. The present disclosure also provides methods of using said compounds and compositions for inhibiting PDE-5 and/or -6 and increasing activity of protein kinase G (PKG). The compounds and compositions find use in therapeutic applications including in the treatment of a variety of eye diseases. For example, the subject compounds may be used as a therapeutic agent for glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), xerophthalmia, cataracts or uveitis. |