Agonists of somatostatin receptor subtype 2 (sst(2)) have been proposed as therapeutics for the treatment of proliferative diabetic retinopathy and exudative age-related macular degeneration. An HTS screen identified 2-quinolones as weak agonists of sst(2), and these were optimized to provide small molecules with sst(2) binding and functional potency comparable to peptide agonists. Agonist 21 was shown to inhibit rat growth hormone secretion following systemic administration and to inhibit ocular neovascular lesion formation after local administration.