Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy

作者：Acharya Suchismita; Rogers Preston; Krishnamoorthy Raghu R; Stankowska Dorota L; Dias H V Rasika^*; Yorio Thomas

来源：Bioorganic & Medicinal Chemistry Letters, 2016, 26(5): 1490-1494.

DOI：10.1016/j.bmcl.2015.12.030

• Glaucoma
• Optic neuropathy
• Catalytic anti-oxidant
• Sydnonimine
• Aceloxy acyl carbamate prodrug
• TEMPOL
• Nitric oxide
• SOD mimetic

Synthesis and bioactivity of novel dual acting nitric oxide releasing and reactive oxygen scavenging hybrid compound SA-2 is described. The hybrid molecule SA-2 significantly increased the superoxide dismutase enzyme level and protected the photoreceptor cells from H2O2 induced oxidative stress. Synthesis of ocular esterase sensitive aceloxy alkyl carbamate prodrug SA-4 with improved aqueous half-life is achieved to aid topical ocular formulation. This class of hybrid molecule and prodrug may have dual potential of improved IOP lowering and neuroprotection in glaucomatous optic neuropathy.

• 出版日期2016-3-1