Suzetrigine Synthesis
Suzetrigine (Synonyms: 4-[[[(2R,3S,4S,5R)-3-(3,4-Difluoro-2-methoxyphenyl)tetrahydro-4,5-dimethyl-5-(trifluoromethyl)-2-furanyl]carbonyl]amino]-2-pyridinecarboxamide)
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).
Suzetrigine
A Nav1.8 inhibitor
Item No. BM42037
CAS No. 2649467-58-1
Purity: 98%
Suzetrigine Synthetic Route
1.1: 1,1'-carbonyldiimidazole / acetonitrile / 1.5 h / -2 - 0 °C / Large scale
1.2: 5 h / 35 °C / Large scale
2.1: palladium-carbon; hydrogen / isopropyl alcohol / 30 h / 30 - 31 °C / 2585.81 - 11636.1 Torr / Large scale
3.1: diisobutylaluminium hydride / toluene / 6.5 h / -31 - -26 °C / Large scale
4.1: triethylamine / toluene / 0 °C
5.1: boron trifluoride diethyl etherate / toluene / 3 h / 20 °C
6.1: isopropyl alcohol; n-heptane / 2 h / 65 - 70 °C / Large scale
7.1: hydrogenchloride / toluene; water / 20 °C
7.2: 4 h / 30 °C
8.1: triethylamine / dichloromethane / 4 h / 25 °C
9.1: ammonia / methanol / 24 h / 20 °C / Large scale
Order Suzetrigine Intermediates
References
1.Current Patent Assignee: VERTEX PHARMACEUTICALS - WO2022/256660, 2022, A1
2.Jones, J., Correll, D.J., Lechner, S.M., et al. Selective inhibition of NaV1.8 with VX-548 for acute pain. N. Engl. J. Med. 389(5), 393-405 (2023).
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