36404-89-4Relevant academic research and scientific papers
Development of oxathiino[6,5-b]pyridine 2,2-dioxide derivatives as selective inhibitors of tumor-related carbonic anhydrases IX and XII
Nocentini, Alessio,Supuran, Claudiu T.,?alubovskis, Raivis,Domra?eva, Ilona,Grandāne, Aiga
, (2020/05/25)
Oxathiino[6,5-b]pyridine 2,2-dioxides are identified as a new class of isoform-selective nanomolar inhibitors of tumor associated human carbonic anhydrases (hCA) IX and XII. At the same time they do not inhibit or poorly inhibit cytosolic isoforms hCA I and II. Oxathiino[6,5-b]pyridine 2,2-dioxides exhibited good antiproliferative properties on tumor cell lines MCF-7 (Human breast adenocarcinoma), A549 (human lung (alveolar) adenocarcinoma) and HeLa (epithelioid cervix carcinoma).
Synthesis and pharmacological evaluation of N-benzyl substituted 4-bromo-2,5-dimethoxyphenethylamines as 5-HT2A/2C partial agonists
Hansen, Martin,Jacobsen, Stine Engesgaard,Plunkett, Shane,Liebscher, Gudrun Eckhard,McCorvy, John D.,Br?uner-Osborne, Hans,Kristensen, Jesper Langgaard
supporting information, p. 3933 - 3937 (2015/01/30)
N-Benzyl substitution of phenethylamine 5-HT2A receptor agonists has dramatic effects on binding affinity, receptor selectivity and agonist activity. In this paper we examine how affinity for the 5-HT2A/2C receptors are influenced by N-benzyl substitution of 4-bromo-2,5-dimethoxyphenethylamine derivatives. Special attention is given to the 2′ and 3′-position of the N-benzyl as such compounds are known to be very potent. We found that substitutions in these positions are generally well tolerated. The 2′-position was further examined using a range of substituents to probe the hydrogen bonding requirements for optimal affinity and selectivity, and it was found that small changes in the ligands in this area had a profound effect on their affinities. Furthermore, two ligands that lack a 2′-benzyl substituent were also found to have high affinity contradicting previous held notions. Several high-affinity ligands were identified and assayed for functional activity at the 5-HT2A and 5-HT2C receptor, and they were generally found to be less efficacious agonists than previously reported N-benzyl phenethylamines.
Tricyclic-isoxazolidine analogues via intramolecular 1,3-dipolar cycloaddition reactions of nitrones
Saubern, Simon,Macdonald, James M.,Ryan, John H.,Woodgate, Ruth C.J.,Louie, Theola S.,Fuchter, Matthew J.,White, Jonathan M.,Holmes, Andrew B.
experimental part, p. 2761 - 2767 (2010/05/02)
The tricyclic-isoxazolidine analogues tetrahydrothiochromenoisoxazoles, hexahydroisoxazolequinolines and tetrahydroisoxazolepyranopyridines were prepared by an intramolecular 1,3-dipolar cycloaddition reaction of a nitrone with an alkene. For N-alkylated hexahydroisoxazolequinolines, reduction of the reaction time from two days to 40 min was achieved using microwave heating. The cyclization to form tetrahydroisoxazolepyranopyridines only proceeded when the alkene was substituted with an electron withdrawing group.
THROMBIN INHIBITING 2-OXO-1, 2, 5, 6-TETRAHYDROPYRIDINE DERIVATIVES
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Page/Page column 60, (2010/11/25)
There is provided a compound of formula (I) wherein R1, R2a, R2b, R3a, R3b, R4, R5a, R5b, R6 to R8, A and G have meanings given in the description, which compounds are useful as, or are useful as prodrugs of, competitive inhibitors of trypsin-like proteases, such as thrombin, and thus, in particular, in the treatment of conditions where inhibition of thrombin is beneficial (e.g. conditions, such as thrombo-embolisms, where inhibition of thrombin is required or desired, and/or conditions where anticoagulant therapy is indicated).
Synthesis of Glutaconaldehydes from Pyridinium Betaines of Squaric Acid
Gruenefeld, J.
, p. 262 - 268 (2007/10/02)
The pyridinium ring of squaric acid betaines (2) is opened by hydroxide ions.Electronegative substituents (R = Cl, CN) at C-3 promote this reaction.The stereochemistry of the resulting 5-(2-hydroxy-3,4-dioxocyclobut-1-en-1-yl)aminopenta-2,4-dienales (3) is confirmed by NMR-spectroscopy.Treatment of 3 with sodium hydroxide results in further hydrolysis to the sodium salts of glutaconaldehydes (5) and 3-amino-4-hydroxycyclobut-3-ene-1,2-dione (6).These products are also directly obtained from the nicotinic acid derivates 2d (R = COOEt) and 2e (R = CONH2), in the latter case cyclisation of the glutaconic acid derivate to the known 3-formylpyrid-2-one (10) is observed.
Improved Synthesis of 2,3-Disubstituted Pyridines by Metallation of 2-Chloropyridine: a Convenient Route to Fused Polyheterocycles
Trecourt, Francois,Marsais, Francis,Guengoer, Timur,Queguiner, Guy
, p. 2409 - 2415 (2007/10/02)
Chemoselective directed metallation of 2-chloropyridine allows the synthesis of 2-substituted 3-carbonylated pyridines, advantage being taken of the metallation ortho-directing effect of the halogen, as well as its reactivity towards nucleophiles.Thus (2-chloro-, 2-methoxy-, and 2-amino-3-pyridyl)-ethanones and -arylmethanones as well as carbaldehydes have been prepared.Some of these ortho-disubstituted intermediates have been readily cyclized to fused polyheterocycles such as naphthiridines and aza-analoges of coumarins, xanthones, and acridones.
Pyridine Nucleotide Chemistry. A New Mechanism for the Hydroxide-Catalyzed Hydrolysis of the Nicotinamide-Glycosyl Bond
Johnson, Randy W.,Marschner, Thomas M.,Oppenheimer, Norman J.
, p. 2257 - 2263 (2007/10/02)
The mechanism of hydroxide-catalyzed hydrolysis of the glycosyl bond of β-NAD+ has been reinvestigated.The pH dependence of the rate of hydrolysis of β-NAD+ and related compounds has been determined over a range from pH 4.3 to 13.5.Between pH 8.5 and 11 the log of the rate constant is linearly dependent on pH with a slope of unity.Below pH 6.5 and above pH 12.5 the reaction becomes pH independent.The product of the reaction over the entire pH range is nicotinamide.A nonlinear least-squares fit of the data yields a pKeq corresponding to the pKa of ionization of the nicotinamide ribose diol, which has been determined independently by 13C NMR.Methanolysis of β-NAD+ yields a ratio of 3.7:1 for the β and α anomers of 1'-O-methyl-ADP ribose.Hydrolysis in a methanol/water mixture shows no selectivity for attack on the basis of the nucleophilicity of the attacking species.The importance of the ribose diol in the hydrolysis reaction was investigated with the isopropylidene derivative of β-nicotinamide riboside.Hydroxide-catalyzed decomposition of β-2',3'-O-isopropylidene nicotinamide riboside is pH independent below pH 7 and linearly dependent on hydroxide concentration above pH 10.In contrast to the results for β-NAD+, no pH-independent region is observed at high pH and the product of the pH-dependent reaction is 2-hydroxy-3-pyridinecarboxaldehyde; i.e., no detectable hydroxide-catalyzed release of nicotinamide is observed.On the basis of these data, as well as solvent isotope effects and data from previous investigations, we propose a new mechanism in which dissociative cleavage of nicotinamide-glycosyl bond is facilitated by the nicotinamide ribose diol anion through noncovalent stabilization of an oxo carbocation intermediate.
The Mechanism of the Reaction of Nicotinic Acid 1-Oxide with Acetic Anhydride
Nagano, Hiroyuki,Nawata, Yoshiharu,Hamana, Masatomo
, p. 4068 - 4077 (2007/10/02)
In order to elucidate the mechanism of the 2-acetylation in the reaction of nicotinic acid 1-oxide (2a) with boiling acetic anhydride, thermal reactions and reactions with hot acetic anhydride have been explored with 3-X-pyridine 1-oxides (2).The former reactions of 2d (X = CONHAc), 2f (X = CONMeAc), 2h (X = CH2OAc) and 2j result in recovery or decomposition.The latter reactions of 2c (X = CONH2), 2d, 2e (X = CONHMe), 2h and 2j bring about mainly deoxygenative α-acetoxylation, no 2-acetylation being noticed.However, the reaction of 2f with acetic anhydride affords 6,7-dihydro-6-methyl-7-methylene-5H-pyrrolopyridin-5-one 1-oxide (7) as an initial product, which further undergoes deoxygenative β-acetoxylation to give 7-acetoxy-7-acetoxymethyl-6,7-dihydro-6-methyl-5H-pyrrolopyridin-5-one (8) and 7-acetoxymethylene-6,7-dihydro-6-methyl-5H-pyrrolopyridin-5-one (9).On the basis of the results we propose a new electrophilic pathway for the 2-acetylation of 2a and 2f.Keywords - pyridine 1-oxide 3-substituted; nicotinic acid 1-oxide; nicotinamide 1-oxide N-acetyl-N-methyl; pyrrolopyridine; 2-acetylation; pyridone formation
