2. Academic Validation
  3. Design, synthesis and characterization of novel N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors leading to the identification of the selective compound, AC1903

Design, synthesis and characterization of novel N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors leading to the identification of the selective compound, AC1903

  • Bioorg Med Chem Lett. 2019 Jan 15;29(2):155-159. doi: 10.1016/j.bmcl.2018.12.007.
Swagat H Sharma 1,  Juan Lorenzo Pablo 2,  Monica Suarez Montesinos 2,  Anna Greka 2,  Corey R Hopkins 3
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, United States.
  • 2 Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States; Broad Institute of MIT and Harvard, Cambridge, MA 02142, United States.
  • 3 Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, United States. Electronic address: [email protected].
PMID: 30538066 DOI: 10.1016/j.bmcl.2018.12.007
Abstract

The transient receptor potential cation channel 5 (TRPC5) has been previously shown to affect podocyte survival in the kidney. As such, inhibitors of TRPC5 are interesting candidates for the treatment of chronic kidney disease (CKD). Herein, we report the synthesis and biological characterization of a series of N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors. Work reported here evaluates the benzimidazole scaffold and substituents resulting in the discovery of AC1903, a TRPC5 inhibitor that is active in multiple animal models of CKD.

Keywords

AC1903; Chronic kidney disease; Inhibitor; TRPC5; Transient receptor potential cation channel 5.

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