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Updated: May 28, 2026
08:49
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Discovery and optimization of indole and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-II)
E Hampton Sessions1, Sarwat Chowdhury, Yan Yin
1Translational Research Institute and Department of Molecular Therapeutics, The Scripps Research Institute, Scripps Florida, 130 Scripps Way, #2A1, Jupiter, FL 33458, USA.
Bioorganic & Medicinal Chemistry Letters
|October 25, 2011
Summary
Novel Rho kinase (ROCK) inhibitors were developed using indole and 7-azaindole scaffolds. These potent ROCK inhibitors show promise for treating diseases like hypertension, stroke, cancer, and glaucoma.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Drug Discovery
Background:
- Rho kinase (ROCK) inhibitors represent a promising therapeutic strategy for various diseases.
- Conditions such as hypertension, stroke, cancer, and glaucoma are potential targets for ROCK inhibitor therapy.
Purpose of the Study:
- To optimize and biologically evaluate novel potent ROCK inhibitors.
- To explore substituted indole and 7-azaindole core scaffolds for ROCK inhibition.
Main Methods:
- Synthesis and structural modification of indole and 7-azaindole derivatives.
- Biological evaluation of synthesized compounds for ROCK inhibitory activity.
- Assessment of in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) properties.
Main Results:
- Several potent and selective ROCK inhibitors (compounds 25, 42, and 50) were identified.
- Strategic substitutions at the indole C3, indole NH, and amide NH positions enhanced inhibitory potency.
- Optimized substitutions improved aqueous solubility and DMPK profiles.
Conclusions:
- Substituted indole and 7-azaindole scaffolds are effective for developing potent ROCK inhibitors.
- Chemical modifications can significantly enhance the drug-like properties of ROCK inhibitors.
- These novel compounds hold potential for treating ROCK-associated disorders.
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