6104-45-6Relevant academic research and scientific papers
POLY-ADP RIBOSE POLYMERASE (PARP) INHIBITORS
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Page/Page column 98; 99, (2018/07/29)
The present invention is related to a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula: The present invention is also related a method of treating a subject with a disease which can be ameliorated by inhibition of poly(ADP-ribose)polymerase (PARP). The definitions of the variables are provided herein.
Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands
Taylor, Nicholas J.,Emer, Enrico,Preshlock, Sean,Schedler, Michael,Tredwell, Matthew,Verhoog, Stefan,Mercier, Joel,Genicot, Christophe,Gouverneur, Véronique
supporting information, p. 8267 - 8276 (2017/06/27)
Molecules labeled with fluorine-18 (18F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated 18F-fluorination of aryl boron reagents with 18F-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of 18F-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally complex pharmaceutically relevant heterocycle-containing molecules.
Discrimination between O-H...N and O-H...O=C Complexes of 3-Methyl-4-pyrimidone and Methanol. A Matrix-isolation FT-IR and Theoretical DFT/B3LYP Investigation
Muzomwe, Mayaliwa,Boeckx, Bram,Maes, Guido,Kasende, Okuma E.
experimental part, p. 23 - 33 (2012/03/27)
FT-IR matrix-isolated spectra for 3-methyl-4-pyrimidone and its H-bonded complexes with methanol in Ar were studied with the aim of discriminating between O-H...N and O-H...O=C complexes. Theoretical calculations were carried out using the DFT/B3LYP/6-31+G(d) methodology in an attempt to predict the preferred interaction site of the 3-methyl-4-pyrimidone molecule with proton donors. The observed frequency decrease of the ν(C=O) mode of 3-methyl-4-pyrimidone and the appearance of a broad (OH...O) band in the spectrum of the complex with methanol suggest that H-bonding with methanol occurs at the carbonyl group. Computed binding energies of the hydrogen-bonded complexes ( Ec) and computed intermolecular distances (r(O...H)) confirm that the O-H...O=C complex is preferred with methanol. However, for H-bonding with stronger acids such as HCl, the computational data suggest that the H-bonding occurs at the N1 ring atom of 3-methyl-4-pyrimidone.
Direct alkenylation and alkylation of pyridone derivatives by Ni/AlMe 3 catalysis
Nakao, Yoshiaki,Idei, Hiroaki,Kanyiva, Kyalo Stephen,Hiyama, Tamejiro
supporting information; experimental part, p. 15996 - 15997 (2010/02/16)
(Chemical Equation Presented) Regioselective alkenylation and alkylation of 2-pyridone derivatives are achieved through inter- and intramolecular insertion of alkynes, 1,3-dienes, and alkenes into the C(6)-H bond by nickel/AlMe 3 catalysis. Coo
On the Chichibabin Amination of Pyrimidine and N-Alkylpyrimidinium Salts Using Liquid Ammonia/Potassium Permanganate
Buurman, Dick J.,Plas, Henk C. van der
, p. 1377 - 1380 (2007/10/02)
Treatment of the 2-R-pyrimidines (1, R = methyl, ethyl, i-propyl and t-butyl) with potassium amide/liquid ammonia/potassium permanganate leads to amination at C-4(6).The yields of the 4(6)-amino compounds 3 increase in the order 2-methyl (10percent), 2-ethyl (30percent), 2-i-propyl (45percent) and 2-t-butyl (60percent).Treatment of the 2-R-N-methylpyrimidinium salts (4, R = hydrogen, methyl) with liquid ammonia/potassium permanganate leads to a regiospecific imination at C-6, the corresponding 2-R-1,6-dihydro-6-imino-1-methylpyrimidines 6 being obtained in 80-85percent yield.It is proved by 15N-labelling that no ring opening is involved in these imination reactions.Treatment of the imino compounds with base leads to the corresponding 2-R-6-methylaminopyrimidines 8, involving, as proved by 15N-labelling, an ANRORC-mechanism. 2-t-Butyl-1-ethylpyrimidinium tetrafluoroborate (9b) when treated with liquid ammonia/potassium permanganate undergoes N-deethylation, 2-t-butylpyrimidine being exclusively formed.
Stereochemical Studies. Part 103. Saturated Heterocycles. Part 107. Preparation of 3-Mono and 2,3-Di-substituted Pyrimidin-4(3H)-ones in Retro-Diels-Alder Reactions. The Correct 1,2-Disubstituted Structure of the Compounds previously described as 2,3-Disu
Stajer, Geza,Szabo, Angela E.,Bernath, Gabor,Sohar, Pal
, p. 237 - 240 (2007/10/02)
The orthofomate cyclization of carboxamides (4) obtained from 3-exo-aminobicyclohept-5-ene-2-exo-carboxylic acid (1) yielded intermediate 8,9,10-trinorbornene-fused pyrimidinones (5) and hence 3-substituted pyrimidin-4(3H)-ones (6) through the spli
Infrared Study of Hydrogen-Bonded Complexes Involving Phenol Derivatives and Polyfunctional Bases. 2. 3-Methyl-4-pyrimidone, 1-Methyl-2-pyrimidone, 1,4,4-Trimethylcytosine, and 1,3-Dimethyluracil
Kasende, O.,Zeegers-Huyskens, Th.
, p. 2636 - 2641 (2007/10/02)
In this work, the electron-donating properties of 3-methyl-4-pyramidone (I), 1-methyl-2-pyramidone (II), 1,4,4-trimethylcytosine (III), 1,3-dimethyluracil (IV), and pyrimidine (V) have been studied by infrared spectrometry, using the phenol derivatives as reference acids.The thermodinamic parameters (K, -ΔH, ΔS) determined in 1,2-dichloethane (1,2-DCE) are ordered according to III > II > IV > V, the same order as that predicted from the pKa value, with the exception of IV.For the same enthalpy of complex formation, the ΔνOH values were markedly higher for V than for the complexes involving the other bases; this fact and the frequency lowering of the νC=O vibration clearly show that for compounds I-IV the carbonyl group is the preferred H-bond site.For IV, the infrared data suggest that complex formation takes place on the O4 atom in agreement with the lower ionization potential of the n(O4) electrons.As shown by the X-ray diffraction method and the infrared spectra available in the literature, protonation takes place on the nitrogen atom for I-III and on the O4 atom for IV.This shows that, with the exception of IV, the preferred H-bonding site is not the preferred site of protonation.The intermolecular streetching vibrations ν? are observed between 130 and 110 cm-1 and the corresponding force constants k? are calculated by the Lippincott-Schroeder potential function.The k? values are compared with those of hydrogen bonds involving nitrogen and sulfur atoms.It is shown that, for the same enthalpy of complexation, the k? values are related to the extension of the lone-pair electrons of the base.
