Gefapixant Chemical Properties

Boiling point:

606.3±65.0 °C(Predicted)

Density 

1.391±0.06 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMSO:38.0(Max Conc. mg/mL);107.53(Max Conc. mM)

pka

9.90±0.60(Predicted)

form 

Solid

color 

White to off-white

InChI

InChI=1S/C14H19N5O4S/c1-7(2)8-4-10(22-3)12(24(17,20)21)5-9(8)23-11-6-18-14(16)19-13(11)15/h4-7H,1-3H3,(H2,17,20,21)(H4,15,16,18,19)

InChIKey

HLWURFKMDLAKOD-UHFFFAOYSA-N

SMILES

C1(S(N)(=O)=O)=CC(OC2=CN=C(N)N=C2N)=C(C(C)C)C=C1OC

Gefapixant Usage And Synthesis

Description

Gefapixant was approved in Japan in 2022 for adult patients with refractory or unexplained chronic cough, marketed under the name Lyfnua.The drug was authorised by the European Medicines Agency (EMA) in September 2023 for the same indication. However, the FDA refused to approve gefapixant for the treatment of adults with refractory or unexplained chronic cough.

Uses

Gefapixant is an orally active and potent purinergic P2X3 receptor (P2X3R) antagonist, with IC50 values of ~30 nM versus recombinant hP2X3 homotrimers and 100-250 nM at hP2X2/3 heterotrimeric receptors. Gefapixant can be used for the research of chronic cough and knee osteoarthritis.

Mechanism of action

Gefapixen is an orally available, selective P2X3 receptor antagonist used to treat cough-related conditions such as chronic cough and refractory cough. The P2X3 receptor is an ion channel expressed in sensory neurons that plays a key role in the transmission of pain and cough reflexes. Gefapixen reduces the activation of cough receptors by specifically blocking the P2X3 receptor, thereby alleviating cough symptoms.

Pharmacokinetics

Gefapixant exerts its therapeutic effects via suppressing the cough reflex initiated by sensory C fibers of the vagus nerve. In clinical studies, patients experienced a significant reduction in 24-hour cough frequency compared to placebo - this reduction was apparent by Week 4 and persisted throughout the remainder of the primary efficacy period. As renal excretion is the primary route of elimination for gefapixant, patients with severe renal impairment (eGFR < 30 mL/min/1.73m2) may require dose adjustment to maintain appropriate systemic exposures.

in vivo

IC 50

P2X3 Receptor