| Identification | Back Directory | [Name]
2-Pyridinecarboxamide, 4-[[[(2R,3S,4S,5R)-3-(3,4-difluoro-2-methoxyphenyl)tetrahydro-4,5-dimethyl-5-(trifluoromethyl)-2-furanyl]carbonyl]amino]- | [CAS]
2649467-58-1 | [Synonyms]
VX-548
Suzetrigine
2-Pyridinecarboxamide, 4-[[[(2R,3S,4S,5R)-3-(3,4-difluoro-2-methoxyphenyl)tetrahydro-4,5-dimethyl-5-(trifluoromethyl)-2-furanyl]carbonyl]amino]- | [EINECS(EC#)]
200-100-8 | [Molecular Formula]
C21H20F5N3O4 | [MOL File]
2649467-58-1.mol | [Molecular Weight]
473.4 |
| Chemical Properties | Back Directory | [Boiling point ]
591.8±50.0 °C(Predicted) | [density ]
1.399±0.06 g/cm3(Predicted) | [solubility ]
Acetonitrile: Slightly Soluble: 0.1-1 mg/ml
DMSO: Sparingly Soluble: 1-10 mg/ml | [form ]
Solid | [pka]
11.74±0.70(Predicted) | [color ]
White to light yellow | [InChIKey]
XSQUJFKRXZMOKA-KRZZIQMTNA-N | [SMILES]
C([C@@H]1O[C@@](C)(C(F)(F)F)[C@@H](C)[C@H]1C1C=CC(F)=C(F)C=1OC)(=O)NC1=CC=NC(C(=O)N)=C1 |&1:1,3,9,11,r| |
| Hazard Information | Back Directory | [Description]
Suzetrigine is an inhibitor of voltage-gated sodium channel 1.8 (Nav1.8; IC50 = 0.7 nM for the human channel).1 It is selective for Nav1.8 over a panel of eight additional voltage-gated sodium channels (IC50s = >10,000 nM for all).WARNING This product is not for human or veterinary use. | [Synthesis]
The synthesis of Suzetrigine (VX-548) revolves around the highly stereoselective construction of its tetrahydropyran core. A typical synthetic route begins with a chiral starting material (e.g., a chiral epoxide) that undergoes a stereoselective addition reaction with a fluoroaryllithium reagent, introducing a phenyl group and a trifluoromethyl group. Subsequently, a nucleophilic cyclization reaction forms the crucial tetrahydropyran ring, thus determining the correct configuration of the four stereocenters. Subsequent steps involve standard organotransformation reactions, such as cross-coupling reactions (e.g., the Suzuki coupling reaction), to introduce the pyridine moiety, ultimately yielding the final Suzetrigine product via deprotection and salt formation. | [References]
[1] JIM JONES. Selective Inhibition of NaV1.8 with VX-548 for Acute Pain.[J]. New England Journal of Medicine, 2023, 389 5: 393-405. DOI: 10.1056/nejmoa2209870 |
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