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

Swagat H. Sharma, Juan Lorenzo Pablo, Monica Suarez Montesinos, Anna Greka, Corey R Hopkins

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)155-159
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume29
Issue number2
DOIs
StatePublished - Jan 15 2019

Fingerprint

Transient Receptor Potential Channels
Amines
Chronic Renal Insufficiency
Podocytes
Scaffolds
Animals
Animal Models
Kidney
imidazole

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

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. / Sharma, Swagat H.; Pablo, Juan Lorenzo; Montesinos, Monica Suarez; Greka, Anna; Hopkins, Corey R.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 29, No. 2, 15.01.2019, p. 155-159.

Research output: Contribution to journalArticle

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