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Literature DB >> 22004718

Discovery and optimization of indoles and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-I).

Sarwat Chowdhury¹, E Hampton Sessions, Jennifer R Pocas, Wayne Grant, Thomas Schröter, Li Lin, Claudia Ruiz, Michael D Cameron, Stephan Schürer, Philip LoGrasso, Thomas D Bannister, Yangbo Feng.

Abstract

Rho kinase (ROCK) inhibitors are potential therapeutic agents to treat disorders such as hypertension, multiple sclerosis, cancers, and glaucoma. Here, we disclose the synthesis, optimization, biological evaluation of potent indole and 7-azaindole based ROCK inhibitors that have high potency on ROCK (IC(50)=1 nM) with 740-fold selectivity over PKA (47). Moreover, 47 showed very good DMPK properties making it a good candidate for further development. Finally, docking studies with a homology model of ROCK-II were performed to rationalize the binding mode of these compounds and showed the compounds bound in both orientations to take advantage to H-bonds with Lys-121 of ROCK-II. Copyright Â

Entities: Chemical Disease Gene

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Year: 2011 PMID： 22004718 DOI： 10.1016/j.bmcl.2011.09.083

Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823

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Cited

7 in total

Review 7. Multitargeting the Action of 5-HT₆ Serotonin Receptor Ligands by Additional Modulation of Kinases in the Search for a New Therapy for Alzheimer's Disease: Can It Work from a Molecular Point of View?

Authors: Kinga Czarnota-Łydka; Katarzyna Kucwaj-Brysz; Patryk Pyka; Wawrzyniec Haberek; Sabina Podlewska; Jadwiga Handzlik
Journal: Int J Mol Sci Date: 2022-08-07 Impact factor: 6.208

7 in total

Discovery and optimization of indoles and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-I).

1. In silico prediction of ROCK II inhibitors by different classification approaches.

2. Identification of Novel Rho-Kinase-II Inhibitors with Vasodilatory Activity.

3. Azaindole therapeutic agents.

4. Discovery of Novel N-Substituted Prolinamido Indazoles as Potent Rho Kinase Inhibitors and Vasorelaxation Agents.

Review 5. The azaindole framework in the design of kinase inhibitors.

6. Prospects of Indole derivatives as methyl transfer inhibitors: antimicrobial resistance managers.

Review 7. Multitargeting the Action of 5-HT₆ Serotonin Receptor Ligands by Additional Modulation of Kinases in the Search for a New Therapy for Alzheimer's Disease: Can It Work from a Molecular Point of View?

Discovery and optimization of indoles and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-I).

1. In silico prediction of ROCK II inhibitors by different classification approaches.

2. Identification of Novel Rho-Kinase-II Inhibitors with Vasodilatory Activity.

3. Azaindole therapeutic agents.

4. Discovery of Novel N-Substituted Prolinamido Indazoles as Potent Rho Kinase Inhibitors and Vasorelaxation Agents.

Review 5. The azaindole framework in the design of kinase inhibitors.

6. Prospects of Indole derivatives as methyl transfer inhibitors: antimicrobial resistance managers.

Review 7. Multitargeting the Action of 5-HT6 Serotonin Receptor Ligands by Additional Modulation of Kinases in the Search for a New Therapy for Alzheimer's Disease: Can It Work from a Molecular Point of View?

Review 7. Multitargeting the Action of 5-HT₆ Serotonin Receptor Ligands by Additional Modulation of Kinases in the Search for a New Therapy for Alzheimer's Disease: Can It Work from a Molecular Point of View?