- NOVEL HETEROCYCLIC ACRYLAMIDES AND THEIR USE AS PHARMACEUTICALS
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The invention relates to novel heterocyclic acrylamide compounds (I), to the preparation of the compounds and intermediates used therein, to the use of the compounds as antibacterial medicaments and pharmaceutical compositions containing the compounds.
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Page/Page column 159
(2011/06/19)
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- Tubulin binding ligands and corresponding prodrug constructs
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A diverse set of tubulin binding ligands have been discovered which are structurally characterized, in a general sense, by a semi-rigid molecular framework capable of maintaining aryl-aryl, pseudo pi stacking distances appropriate for molecular recognition of tubulin. In phenolic or amino form, these ligands may be further functionalized to prepare phosphate esters, phosphate salts, and phosphoramidates capable of demonstrating selective targeting and destruction of tumor cell vasculature.
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- Tautomerism of the Monohydroxy Derivatives of Five-Membered O, N, and S Heterocycles
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The O-deuterated enolic tautomers 3-deuteroxybenzofuran, 3-deuteroxybenzothiophene, 3-deuteroxyindole, 3-deuteroxy-1-methylindole, 3-deuteroxyfuran, 3-deuteroxythiophene, 2-deuteroxybenzothiophene, and 2-deuteroxythiophene have been generated in solution in mixtures of CD3COCD3, CD3CN, or CD3SOCD3 with D2O by hydrolysis of their trimethylsilyl derivatives in the presence of DCl (1E-3 - 1E-4 M) and characterized by 1H NMR spectroscopy.Solutions of 3-hydroxypyrrole and of 3-hydroxy-1-methylpyrrole were obtained by methanolysis of their trimethylsilyl derivatives,evaporation of the methanol, and immediate dissolution in DMSO-d6.The carbocyclic analogues of the bicyclic heterocyclic enols 3-deuteroxyindene and 2-deuteroxyindene were also generated in solution.Attempts to prepare solutions of 2-deuteroxyfuran, 2-deuteroxypyrrole, and 2-deuteroxy-1-methylpyrrole were unsuccessful.The kinetics of ketonization of the OH forms of these enols have been investigated in water or aqueous acetonitrile solution.The equilibrium constants for the keto-enol tautomerism were also determined either by direct measurement when sufficient enol was present at equilibrium or as the ratio of the rate constant for enolization of the keto form to that for ketonization of the enol form, the former being determined by the iodine-trapping technique.The effect of solvent on the equilibrium constants was also studied.Sufficient data were available for the equilibrium between 3-hydroxyindole and 3-ketoindole for them to be analyzed by the four-parameter equation of Mills and Beak to yield an a value of 2.4 and a b value of -3.0.The pKas of the bicyclic enols were measured. 3-Hydroxybenzofuran and3-hydroxybenzothiophene are stronger acids than 3-hydroxyindole and 3-hydroxy-1-methylindole.The ketonization reactions are general acid and general base catalyzed and their mechanisms are discussed.
- Capon, Brian,Kwok, Fu-Chiu
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p. 5346 - 5356
(2007/10/02)
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- γ-Radiolysis of Aqueous Benzothiophene Solutions
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γ-Radiolysis of aqueous benzothiophene solutions saturated with N2O has been studied.In the absence of other reagents, the only products detected are 2- and 3-hydroxybenzothiophene and their corresponding lactonic and ketonic tautomers and a small amount of dimeric species.In the presence of potassium hexacyanoferrate or sodium hydroxide, however, products attributable to hydroxylation at all six available carbon sites are detected and dimer formation is reduced.Analysis of the experimental data suggests that both benzothiophene and its hydroxylation products are efficient scavengers for the radiation-produced OH radicals and that the initial yield of hydroxylation products is equal to that of hydroxyl radicals.Consistent with the electrophilic characteristics of the OH radical, k(OH+C8H6S):k(OH+C8H5SOH)=0.5+/-0.1.All six available carbon sites are capable of forming OH adducts, but the radicals formed by addition to the 4, 5, 6, and 7 positions tend to revert to the original compound or its ion in a neutral or acidic medium.In the case of the adducts formed by addition to the thiophene ring, on the other hand, the 3 position is seen to be favored, possibly as the result of the preservation of the aromatic benzene resonance structure.
- Feng, Paul Y.,Patel, Kundan,Kaplan, Louis,Matheson, Max S.
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p. 2098 - 2103
(2007/10/02)
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