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Abstract #56525 Published in IGR 16-1
In vivo optimization of 2,3-diaminopyrazine Rho Kinase inhibitors for the treatment of glaucoma
Chen HH; Namil A; Severns B; Ward J; Kelly C; Drace C; McLaughlin MA; Yacoub S; Li B; Patil R; Sharif N; Hellberg MR; Rusinko A; Pang IH; Combrink KDBioorganic and Medicinal Chemistry Letters 2014; 24: 1875-1879
A series of 2,3,6-pyrazine Rho Kinase inhibitors were optimized for in vivo activity for topical ocular dosing. Modifications of the 2-(piperazin-1-yl)pyrazine derivatives produced compounds with improved solubility and physicochemical properties. Modifications of the 6-pyrazine substituent led to improvements in in vitro potency. Compound 9 had the best in vitro and in vivo potency of EC50=260 nM with a 30% reduction of IOP in a non-human primate model at a dose of 0.33%.
Full article
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
