78592-91-3Relevant articles and documents
Synthesis, Reactivity, Functionalization, and ADMET Properties of Silicon-Containing Nitrogen Heterocycles
Barraza, Scott J.,Denmark, Scott E.
supporting information, p. 6668 - 6684 (2018/06/12)
Silicon-containing compounds have been largely ignored in drug design and development, despite their potential to improve not only the potency but also the physicochemical and ADMET (absorption, distribution, metabolism, excretion, toxicity) properties of drug-like candidates because of the unique characteristics of silicon. This deficiency is in large part attributable to a lack of general methods for synthesizing diverse organosilicon structures. Accordingly, a new building block strategy has been developed that diverges from traditional approaches to incorporation of silicon into drug candidates. Flexible, multi-gram-scale syntheses of silicon-containing tetrahydroquinoline and tetrahydroisoquinoline building blocks are described, along with methods by which diversely functionalized silicon-containing nitrogen heterocycles can be rapidly built using common reactions optimized to accommodate the properties of silicon. Furthermore, to better clarify the liabilities and advantages of silicon incorporation, select compounds and their carbon analogues were challenged in ADMET-focused biological studies.
MACROCYCLIC CARBOXYLIC ACIDS AND ACYLSULFONAMIDES AS INHIBITORS OF HCV REPLICATION
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Page/Page column 118, (2008/06/13)
The present invention provides compounds of the general formulas I-IX, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The present invention further provides treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.
Thermal Electrocyclic Reactions of 2-Aza-1,3-butadiene Derivatives. A New N-Heterocyclic Annelation
Govindan, C. K.,Taylor, Grant
, p. 5348 - 5354 (2007/10/02)
A general, three-step annelation sequence, which ultimately gives 3,4-dihydro-2-quinolines and related derivatives (3), is described.The cyclization step is accomplished by pyrolysis of a 1-arenyl-2-aza-1,3-butadiene analogue (2) that apparently undergoes successive six-?-electron electrocyclization and 1,5-hydrogen migration reactions to yield the product.The conjugated azadienes, 2, are prepared by the base-catalyzed isomerization of the unconjugated isomers, 1.Compounds 1 are prepared by condensing arenyl ketones or aldehydes with 2-propenyl-1-amine.Steric effects of substituents on the azadiene chain and steric and electronic effects of the arenyl group on the cyclization step were studied.The following general conclusions were drawn: alkyl substituents R on the C=N terminus of 2 hinder a competing degradative process (commencing with a four-?-electron electrocyclization) and improve the yield of products 3; electron-withdrawing substituents on Ar of 2 or electron-withdrawing Ar groups enhance the yield of cyclized products, but they impart little regioselectivity to the reaction; regioselectivity may be imparted by ? bond fixation in Ar; electrocyclization also proceeds well with ?-electron excessive Ar groups on 2.The preferred conformation of the heterocyclic product 3 can be readily deduced by 1H NMR spectroscopy.
