ROCK inhibitors 3: Design, synthesis and structure-activity relationships of 7-azaindole-based Rho kinase (ROCK) inhibitors

  • Bioorg Med Chem Lett. 2018 Aug 15;28(15):2622-2626. doi: 10.1016/j.bmcl.2018.06.040.
Upul K Bandarage  1 ,  Jingrong Cao  2 ,  Jon H Come  2 ,  John J Court  2 ,  Huai Gao  2 ,  Marc D Jacobs  2 ,  Craig Marhefka  2 ,  Suganthi Nanthakumar  2 ,  Jeremy Green  3
Affiliations
  • 1. Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA. Electronic address: [email protected].
  • 2. Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • 3. Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA. Electronic address: [email protected].
PMID: 30082069 DOI: 10.1016/j.bmcl.2018.06.040
Abstract

Rho kinase (ROCK) inhibitors are potential therapeutic agents for the treatment of a variety of disorders including hypertension, glaucoma and erectile dysfunction. Here we disclose a series of potent and selective ROCK inhibitors based on a substituted 7-azaindole scaffold. Substitution of the 3-position of 7-azaindole led to compounds such as 37, which possess excellent ROCK inhibitory potency and high selectivity against the closely related kinase PKA.

Keywords
7-Azaindole; Lipophilic efficiency; ROCK; Rho kinase; Solubilizing group; Structure-based design.
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