Gefapixant API is a synthetic, orally active, selective P2X3 purinergic receptor antagonist. It was developed to reduce sensory nerve signaling associated with the cough reflex and is primarily associated with the treatment of refractory chronic cough (RCC) and unexplained chronic cough (UCC). Gefapixant is also known by the development codes AF-219, MK-7264 and RO4926219.
Gefapixant has the molecular formula C₁₄H₁₉N₅O₄S, molecular weight 353.40 g/mol, and CAS Registry Number 1015787-98-0. FDA's substance registry and PubChem confirm these identity parameters.
For pharmaceutical formulation, Gefapixant Citrate is the salt form used in the marketed/authorized medicinal product. Gefapixant citrate has CAS 2310299-91-1, molecular formula C₁₄H₁₉N₅O₄S·C₆H₈O₇, and molecular weight 545.52 g/mol. The EMA documentation identifies gefapixant citrate as the active substance supplied in the formulation.
| Property | Value |
|---|---|
| API Name | Gefapixant |
| CAS Number | 1015787-98-0 |
| Development Codes | AF-219 / MK-7264 / RO4926219 |
| Molecular Formula | C₁₄H₁₉N₅O₄S |
| Molecular Weight | 353.40 g/mol |
| Chemical Class | Benzenesulfonamide / Pyrimidine Derivative |
| Pharmacological Class | P2X3 Receptor Antagonist |
| Stereochemistry | Achiral |
| Salt Form | Gefapixant Citrate |
| Citrate CAS | 2310299-91-1 |
| Citrate Molecular Weight | 545.52 g/mol |
The free base is achiral and has no defined stereocenters.
Gefapixant selectively antagonizes the P2X3 receptor, an ATP-gated ion channel expressed on sensory neurons. ATP released during airway irritation or inflammation can activate P2X3 receptors and contribute to stimulation of the cough reflex.
By blocking P2X3-mediated signaling, gefapixant reduces the excessive sensory signaling associated with chronic cough.
Gefapixant has been developed for adults with refractory chronic cough and unexplained chronic cough. It received regulatory approvals in several countries outside the United States; however, the FDA's 2023 advisory documentation states that gefapixant was not FDA-approved in the United States at that time.
The API is relevant to:
| Parameter | Specification |
|---|---|
| Appearance | White to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Heavy Metals | NMT 20 ppm |
| pH (1% Solution) | 5.0 – 7.0 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 2.0% |
| Water Content | NMT 2.0% |