Chroman-3-amides as potent Rho kinase inhibitors

Yen Ting Chen; Thomas D Bannister; Amiee Weiser; Evelyn Griffin; Li Lin; Claudia Ruiz; Michael D Cameron; Stephan Schürer; Derek Duckett; Thomas Schröter; Philip LoGrasso; Yangbo Feng

doi:10.1016/j.bmcl.2008.10.080

Chroman-3-amides as potent Rho kinase inhibitors

Bioorg Med Chem Lett. 2008 Dec 15;18(24):6406-9. doi: 10.1016/j.bmcl.2008.10.080. Epub 2008 Oct 22.

Authors

Yen Ting Chen¹, Thomas D Bannister, Amiee Weiser, Evelyn Griffin, Li Lin, Claudia Ruiz, Michael D Cameron, Stephan Schürer, Derek Duckett, Thomas Schröter, Philip LoGrasso, Yangbo Feng

Affiliation

¹ Department of Molecular Therapeutics, The Scripps Research Institute, Florida, 130 Scripps Way, #2A1, Jupiter, FL 33458, USA.

PMID: 18990570
DOI: 10.1016/j.bmcl.2008.10.080

Abstract

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 activity, good microsomal stability, and desirable pharmacokinetic properties for study as potential therapeutic agents.

MeSH terms

Amides / chemical synthesis*
Amides / pharmacokinetics*
Animals
Chemistry, Pharmaceutical / methods
Chromans / chemical synthesis*
Chromans / chemistry
Chromans / pharmacology*
Drug Design
Glaucoma / drug therapy*
Humans
Inhibitory Concentration 50
Models, Chemical
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / pharmacokinetics
Rats
Time Factors
rho-Associated Kinases / antagonists & inhibitors*

Substances

Amides
Chromans
Protein Kinase Inhibitors
rho-Associated Kinases