Synthesis of GR 125487, a selective 5-HT₄ receptor antagonist

ABSTRACT

The 5-HT₄ receptor (5-HT₄R) agonists are important in treating gastrointestinal motility disorders. Their role is currently being evaluated for the treatment of cognitive and mood disorders. A selective 5-HT₄R antagonist GR 125487 is used in many biological assays to cross confirm the 5-HT₄R agonist’s activity. A practical synthesis of GR 125487 is developed so as to have it in desired quantities. The synthesis consists of seven steps starting from commercially available methyl 5-fluoroindole 3-carboxylate. The GR 125487 thus synthesized was used in blocking the activity of 5-HT₄R agonist compound in animal models of cognition.

GRAPHICAL ABSTRACT

KEYWORDS:

• Alzheimer’s disease
• animal models of cognition
• GR 125487
• selective 5-HT₄R antagonist

Acknowledgment

The support from the analytical chemistry team and moral and financial support received from Venkateswarlu Jasti, CEO, Suven Life Sciences Ltd., Hyderabad is greatly acknowledged.