86556-09-4Relevant articles and documents
Orthogonal Cu- and Pd-based catalyst systems for the O- and N-arylation of aminophenols
Maiti, Debabrata,Buchwald, Stephen L.
supporting information; experimental part, p. 17423 - 17429 (2010/03/25)
O- or N-arylated aminophenol products constitute a common structural motif in various potentially useful therapeutic agents and/or drug candidates. We have developed a complementary set of Cu- and Pd-based catalyst systems for the selective O- and N-arylation of unprotected aminophenols using aryl halides. Selective O-arylation of 3- and 4-aminophenols is achieved with copper-catalyzed methods employing picolinic acid or CyDMEDA, trans-N,N′-dimethyl-1,2- cyclohexanediamine, respectively, as the ligand. The selective formation of N-arylated products of 3- and 4-aminophenols can be obtained with BrettPhos precatalyst, a biarylmonophosphine-based palladium catalyst. 2-Aminophenol can be selectively N-arylated with CuI, although no system for the selective O-arylation could be found. Coupling partners with diverse electronic properties and a variety of functional groups can be selectively transformed under these conditions.
N- and N- Sulfonamides: Potent Orally Active Leukotriene D4 Antagonists of Novel Structurs
Musser, John H.,Kreft, Anthony F.,Bender, Reinhold H. W.,Kubrak, Dennis M.,Carlson, Richard P.,et al.
, p. 1176 - 1183 (2007/10/02)
Two series of compounds, N- sulfonamides and N- sulfonamides, were prepared as leukotriene D4 (LTD4) antagonists.In the phenyl series, N--trifluoromethanesulfonamide (Wy-48,252, 16) was the most potent inhibitor of LTD4-induced bronchoconstriction in the guinea pig.With an intragastric ID 50 of 0.1 mg/kg (2-h pretreatment), 16 was 300 times more potent than LY-171,883.Compound 16 also intragastrically inhibited ovalbumin-induced bronchoconstriction in the guinea pig with an ID 50 of 0.6mg/kg.In vitro against LTD4-induced contraction of isolated guinea pig trachea pretreated with indomethacin and L-cysteine, 16 produced a pKB value of 7.7.In the rat PMN assay 16 inhibited both 5-lipoxygenase and cyclooxygenase (IC 50's = 4.6 and 3.3 μM).In the naphthyl series, N-trifluoromethanesulfonamide (Wy-48,090, 47) in addition to potent LTD4 antagonist activity (on isolated guinea pig trachea 47 had a pKB value of 7.04) also had antiinflammatory activity (63percent inhibition at 50 mg/kg in the rat carrageenan paw edema assay and 34percent inhibition of TPA-induced inflammation at 1 mg/ear in the mouse ear edema model).Perhaps the antiinflammatory activity of 47 was due to its additional activity of inhibiting both 5-lipoxygenase and cyclooxygenase enzymes (IC 50's = 0.23 and 11.9 μM, respectively, in rat PMN).
