Further Exploration of the Benzimidazole Scaffold as TRPC5 Inhibitors: Identification of 1‐Alkyl‐2‐(pyrrolidin‐1‐yl)‐1H‐benzoimidazoles as Potent and Selective Inhibitors

The transient receptor potential cation channel 5 (TRPC5) plays an important role in numerous cellular processes. Due to this, it has gained considerable attention over the past few years as a potential therapeutic target. Recently, TRPC5 has been shown to be involved in the regulation of podocyte s...

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Bibliographic Details
Published in:ChemMedChem 2022-07, Vol.17 (14)
Main Authors: Sharma, Swagat, Pablo, Juan L, Tolentino, Kirsten T, Gallegos, Wacey, Hinman, Jennifer, Madison Beninato, MacKenzie Asche, Greka, Anna, Hopkins, Corey R
Format: Article
Language:English
Subjects:
Aminobenzimidazole
Benzimidazoles
Inhibitors
Ion channels
Kidney diseases
Pain
Scaffolds
Sensory neurons
Therapeutic targets
Transient receptor potential proteins
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Summary:The transient receptor potential cation channel 5 (TRPC5) plays an important role in numerous cellular processes. Due to this, it has gained considerable attention over the past few years as a potential therapeutic target. Recently, TRPC5 has been shown to be involved in the regulation of podocyte survival, indicating a potential treatment option for chronic kidney disease. In addition, a recent study has shown TRPC5 to be expressed in human sensory neurons and suggests that TRPC5 inhibition could be an effective treatment for spontaneous and tactile pain. To understand these processes more fully, potent and selective tool compounds are needed. Herein we report further exploration of the 2‐aminobenzimidazole scaffold as a potent TRPC5 inhibitor, culminating in the discovery of 16 f as a potent and selective TRPC5 inhibitor.
ISSN:1860-7179
1860-7187
DOI:10.1002/cmdc.202200151