1072906-05-8Relevant articles and documents
Synthesis and biological evaluation of urea derivatives as highly potent and selective rho kinase inhibitors
Yin, Yan,Lin, Li,Ruiz, Claudia,Khan, Susan,Cameron, Michael D.,Grant, Wayne,Pocas, Jennifer,Eid, Nibal,Park, Hajeung,Schr?ter, Thomas,Lograsso, Philip V.,Feng, Yangbo
, p. 3568 - 3581 (2013/06/27)
RhoA and its downstream effector ROCK mediate stress fiber formation and cell contraction through their effects on the phosphorylation of myosin light chain (MLC). Inhibition of the RhoA/ROCK pathway has proven to be a promising strategy for several indications such as cardiovascular disease, glaucoma, and inflammatory disease. In 2010, our group reported urea-based ROCK inhibitors as potential antiglaucoma agents. These compounds showed potent IC50 values in enzymatic and cell-based assays and significant intraocular pressure (IOP)-lowering effects in rats (～7 mmHg).(22) To develop more advanced ROCK inhibitors targeting various potential applications (such as myocardial infarction, erectile dysfunction, multiple sclerosis, etc.) in addition to glaucoma, a thorough SAR for this urea-based scaffold was studied. The detailed optimization process, counter-screening, and in vitro and in vivo DMPK studies are discussed. Potent and selective ROCK inhibitors with various in vivo pharmacokinetic properties were discovered.
UREA AND CARBAMATE COMPOUNDS AND ANALOGS AS KINASE INHIBITORS
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Page/Page column 50-51, (2010/04/27)
The invention is directed to compounds that can inhibit the bioactivity of one or more kinases such as any of Rho kinases, PKB (Akt) kinases, p70S6K kinase, LIM kinases, or IKK kinases, to methods of use of those compounds, and to methods of preparation of those compounds The inventive compounds can be used In the treatment of a variety of medical malconditions.
Chroman-3-amides as potent Rho kinase inhibitors
Chen, Yen Ting,Bannister, Thomas D.,Weiser, Amiee,Griffin, Evelyn,Lin, Li,Ruiz, Claudia,Cameron, Michael D.,Schuerer, Stephan,Duckett, Derek,Schroeter, Thomas,LoGrasso, Philip,Feng, Yangbo
scheme or table, p. 6406 - 6409 (2009/10/01)
Inhibition of Rho kinase (ROCK) is an attractive strategy for the treatment of diseases such as hypertension, glaucoma, and cancer. Here we report chroman-3-amides as highly potent ROCK inhibitors with sufficient kinase selectivity, excellent cell activit
