- Enols of 2-nitro- and related 2-substituted malonamides
-
The structures of 2-substituted malonamides, YCH(CONR1R 2)CONR3R4 (Y=Br, SO2Me, CONH 2, COMe, and NO2) were investigated. When Y=Br, R 1R2=R3R4=HEt; Y=SO2Me, R1-R4=H and for Y=CONH2 or CONHPh, R 1-R4=Me, the structure in solution is that of the amide tautomer. X-ray crystallography shows solid-state amide structures for Y=SO 2Me or CONH2, R1-R4=H. Nitromalonamide displays an enol structure in the solid state with a strong hydrogen bond (O. . .O distance=2.3730 A at 100 K) and d(OH) 6≠d(O. . .H). An apparently symmetric enol was observed in solution, even in appreciable percentages in highly polar solvents such as DMSO-d6, but Kenol values decrease on increasing the solvent polarity. The N,N′-dimethyl derivative is less enolic. Acetylmalonamides display a mixture of enol on the acetyl group and amide in non-polar solvents, and only the amide in DMSO-d6. DFT calculations gave the following order of pKenol values for Y: H > CONH 2 > COMe ≥ COMe (on acetyl) ≥ MeSO2>CN> NO2 in the gas phase, CHCl3, and DMSO. The enol on the C=O group is preferred to the aci-nitro compound, and theN-O-H. . .O=C is less favored than the C=O-H. . .O=C hydrogen bond. Copyright
- Basheer, Ahmad,Mishima, Masaaki,Rappoport, Zvi
-
experimental part
p. 255 - 265
(2010/09/07)
-
- USE OF AMPK-ACTIVATING IMIDAZOLE DERIVATIVES, PREPARATION PROCESS THEREFOR AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM
-
The invention relates to the use of imidazole derivatives of the formula (I): in which A, R'1, R'2 and R'3 are as defined in the description, as AMPK activators. The invention also relates to processes for the preparation of the said compounds, to their uses for the preparation of medicaments for the treatment of insulin resistance, diabetes and related pathologies, and also obesity, and to the pharmaceutical compositions comprising them. Certain compounds of the formula (I) are novel and, in this respect, also form part of the invention.
- -
-
Page/Page column 24; 45-46
(2008/06/13)
-
- Substituted pyrazole derivatives condensed with six-membered heterocyclic rings
-
The present invention relates to novel substituted pyrazole derivatives of the general formula (I) in which R1, R2, R3and A are each as defined, and to processes for their preparation and to their use as medicaments, in pa
- -
-
Page column 36-37
(2010/02/07)
-
- Electrophilic Substitution in Malonamide. Evidence for Reaction via the Enol Tautomer
-
The kinetics of the nitrosation, bromination and iodination of malonamide have been studied in water at 25 deg C.Throughout, reaction was first order in .At low acidity and relatively high , reactions were fully zero-order in and acid-catalysed.At higher acidity and lower reaction was first-order in and not now acid-catalysed.Similar first-order behaviour was found for bromination and nitrosation (by BrNO and ONSCN generated in situ).It was not possible by changing the reaction conditions to achieve the zero-order pattern with either bromination or nitrosation.The results are consistent with a mechanism involving reaction of the electrophile with an intermediate derived from MA which we suggest is the enol tautomer.For iodination either enolisation or reaction of the enol can be made rate-limiting.For enolisation the value of the rate constant ke (in Rate = ke+>) was found to be 3.3 * 10-3 dm3 mol-1 s-1.The results also suggest that I2, Br2, BrNO and ONSCN react with the enol at or close to the encounter controlled limit, enabling a value for KE (the equilibrium constant for enolisation) of (4 +/- 2) * 1010 to be obtained.The methylene protons in MA are readily exchanged with D from the solvent in an acid catalysed process.The enolisation of CD2(COND2)2 is slower than that of CH2(CONH2)2 by a factor of 2.3 and the deuterium solvent isotope effect is close to 1.The mechanism of enolisation of MA is discussed.
- Williams, D. Lyn H.,Xia, Ling
-
p. 1429 - 1432
(2007/10/02)
-