5496-66-2Relevant academic research and scientific papers
NOVEL DRUGS FOR DEMENTIA
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Example 2, (2008/06/13)
The invention is directed to compounds that are prodrugs containing a chemical delivery system (CDS) moiety and a cysteine protease inhibitor moiety. The CDS moiety targets the prodrug to the brain or central nervous system. The cysteine protease inhibitor inhibits cysteine proteases upon release from the prodrug. Cysteine protease inhibitors are effective for treating dementia, Alzheimer's disease and vascular dementia. Targeting the brain or central nervous system offers significant advantages in treating these conditions and diseases. A preferred CDS prodrug is a dihydrotrigoneline CDS moiety coupled to an epoxysuccinyl peptide cysteine protease inhibitor moiety.
Kinetic and thermodynamic control of pseudobase formation from C-3 substituted 1-methylquinolinium cations
Bunting, John W.,Fitzgerald, Norman P.
, p. 1301 - 1307 (2007/10/02)
The kinetic and thermodynamic control of pseudobase formation from 3-W-1-methylquinolinium cations has been studied for a variety of substituents (W).Spectral data indicate that, in both aqueous and methanolic solution, the C-2 pseudobases predominate at equilibrium for W=H and Br, while the C-4 pseudobases are thermodynamically preferred species for W=CONH2, CO2CH3, CN, and NO2.Stopped-flow studies indicate that in all cases the C-2 pseudobases are the kinetically-controlled products upon basification of the aqueous solutions of these cations.Equilibrium constants (pKR+) have been measured for pseudobase formation at both C-2 and C-4 for each W in all cases where they are experimentally accessible.Substituent effects upon pK2R+ correlate with ?m for W, while pK4R+ depends upon ?-p.These substituent effects allow the prediction of pK2R+ = 15.4 and pK4R+ = 17.4 for the 1-methylquinolinium cation.Rates of C-2 to C-4 pseudobase equilibration have been measured in all cases where the latter species is thermodinamically more stable.These kinetic data allow the evaluation of rate constants for C-4 pseudobase equilibration with each cation.In all cases except W=CN, C-2 pseudobase formation is complete within the mixing time of the stopped-flow instrument.
Regioselectivity of Hydride Transfer to and between NAD+ Analogues
Roberts, R. M. G.,Ostovic, D.,Kreevoy, M. M.
, p. 2053 - 2056 (2007/10/02)
The reaction of 1-methyl- or 1-benzylquinolinium compounds, also bearing an electron-withdrawing substituent in the 3-position, with NaBH4, gives mixtures of the corresponding 1,2-dihydroquinolines and 1,4-dihydroquinolines in which the 1,2-dihydro derivatives usually predominate.The 1,2-derivatives can be isolated.The 1,2-isomers react with the quinolinium salts, giving the 1,4-isomers and regenerating quinolinium salts.This bimolecular isomerization can be used to convert a mixture of isomers to the 1,4-isomer on a preparative scale. 3-Cyano-1,2-dihydro-1-methylquinoline also isomerizes to the 1,2-isomer in the crystalline solid.The major first product of NaBH4 reduction of 3-(aminocarbonyl)-1-benzylpyridinium ion is the 1,6-dihydro derivative.This also isomerizes to the 1,4-dihydro compound in the presence of the pyridinium ion.Reduction of quinolinium derivatives with Na2S2O4 or a dihydropyridine directly produces the 1,4-isomer predominantly.Reduction of 3-(aminocarbonyl)-1-benzylpyridinium ion with Na2S2O4 in D2O gives the 1,4-dihydro derivative, but 8percent of the deuterium is in the 2-position; presumably by reversible isomerization.This deuterium redistribution may have important consequences for the interpretation of isotope effects.
