28478-26-4Relevant articles and documents
SMALL MOLECULE PROSTAGLADIN TRANSPORT INHIBITORS
-
Paragraph 0169-0170; 0196-0197, (2021/05/15)
The disclosure provides compounds of Formula 1, and the pharmaceutically acceptable salts thereof. The variables in Formula 1, e.g. X1-X5, A1, A2, and R1-R4 are described herein. Such compounds are useful as prostaglandin transport (PGT) inhibitors. The disclosure further includes pharmaceutical compositions comprising a compound of Formula 1 or salt thereof and methods of using compounds of Formula 1 and salts thereof to treat diseases and disorders mediated, at least in part, by prostaglandin levels or cyclooxygenase activity. Such diseases and disorders include painful and inflammatory conditions.
Regiospecific synthesis of neuroprotective 1,4-benzoxazine derivatives through a tandem oxidation-Diels-Alder reaction
Nguyen, Khac Minh Huy,Schwendimann, Leslie,Gressens, Pierre,Largeron, Martine
, p. 3749 - 3756 (2015/03/30)
The tandem oxidation-inverse electron demand Diels-Alder reaction of o-aminophenol derivatives and enamines has been accomplished at room temperature using a stoichiometric amount of manganese dioxide as the oxidant to furnish highly substituted 1,4-benzoxazine cycloadducts with complete regiochemical control. Because of its efficiency in introducing diverse elements in both cycloaddition partners, this one-pot process should allow the assembly of libraries of biologically relevant 1,4-benzoxazine derivatives. In this respect, the 3,3-diphenyl-substituted-1,4-benzoxazine derivative 3n was found to be a potent neuroprotective agent in an animal model of excitotoxic lesions in newborn mice.
Unusual Directive Effects in the Hydroboration of β,β-Disubstituted Enamines. Conversion of α-Substituted Aldehydes to the Corresponding Alkenes and β-Amino Alcohols
Singaram, Bakthan,Goralski, Christian T.,Fisher, Gary B.
, p. 5691 - 5696 (2007/10/02)
A comprehensive study of the conversion of β,β-disubstituted enamines into the corresponding alkenes and β-amino alcohols by hydroboration-elimination and hydroboration-oxidation, respectively, has been carried out.The amine moiety of β,β-disubstituted enamines was found to exert a decisive influence on the regioselectivity of the hydroboration reaction involving borane methyl sulfide (BMS).Thus, in the hydroboration of morpholino and piperidino enamines, the boron atom is initially placed predominantly in the α-position.Conversely, the pyrrolidino enamines direct the boron atom exclusively to the β-position.Three oxidizing agents, trimethylamine N-oxide, sodium perborate, and 30 percent hydrogen peroxide-solid sodium hydroxide, were tried in order to optimize the oxidation of the intermediate organoborane derivatives to the corresponding amino alcohols.Our results clearly indicated that 30 percent hydrogen peroxide-solid sodium hydroxide is best suited for this transformation.The yield of amino alcohol ranged from good to essentially quantitative.Enamines derived from β-aryl aldehydes, upon hydroboration with BMS followed by methanolysis and oxidation with neutral hydrogen peroxide, gave the corresponding 1,1-disubstituted alkenes.Contrary to the regioselectivity observed in the hydroboration reactions involving BMS, the hydroboration of β,β-disubstituted enamines using 9-borabicyclononane (9-BBN) gave the trialkylborane intermediates in which the boron atom was placed exclusively at the β-position regardless of the amine moiety of the enamine.These trialkylborane derivatives were very stable and did not undergo the usual elimination reaction with either methanol or sodium hydroxide.However, on thermal decomposition, these afforded the corresponding 1,1-disubstituted alkenes in high yields.
