Abstract
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%.
Original language | English |
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Pages (from-to) | 1875-1879 |
Number of pages | 5 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 24 |
Issue number | 8 |
DOIs | |
State | Published - 15 Apr 2014 |
Keywords
- Glaucoma
- IOP reduction
- Pyrazine
- Rho Kinase