A general carbometalation, three component coupling strategy for the synthesis of alpha,beta-unsaturated gamma-sultines including thio-rofecoxib, a selective COX-2 inhibitor.
Magnesium mediated carbometalation (Grignard addition) to appropriate propargyl alcohols to synthesize a cross-section of variably substituted alpha,beta-unsaturated gamma-sultines is described. Thio-rofecoxib, a selective COX-2 inhibitor (12), is synthesized by this method and its IC(50), microM COX-1 and COX-2 inhibition, and whole blood stability values reported.
Smil
David V
DV
Methyl Gene Inc., 7220 Frederick Banting, Montreal, Québec, Canada H4S 2A1.
Souza
Fabio E S
FE
Fallis
Alex G
AG
D002244:Carbon / Q000737:chemistry; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology; D008274:Magnesium / Q000737:chemistry; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D013450:Sulfones / Q000138:chemical synthesis* / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D002244:Carbon; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D008274:Magnesium