A practical synthesis of m-prostaglandin E synthase-1 inhibitor MK-7285.
A practical, kilogram-scale chromatography-free synthesis of mPGE synthase I inhibitor MK-7285 is described. The route features a convergent assembly of the core phenanthrene unit via amide-directed ortho-metalation and proximity-induced anionic cyclization, followed by imidazole synthesis and late-stage cyanation.
Department of Process Research, Merck Frosst Centre for Therapeutic Research, 16711 Route Transcanadienne, Kirkland, Québec, Canada H9H 3L1. francis_gosselin@merck.com
Francis
F
Gosselin
Stephen
S
Lau
Christian
C
Nadeau
Thao
T
Trinh
Paul D
PD
O'Shea
Ian W
IW
Davies
D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry*; D019746:Intramolecular Oxidoreductases / Q000737:chemistry*; D015394:Molecular Structure; D000071876:Prostaglandin-E Synthases
D004791:Enzyme Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; C545690:MK-7285; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases