Quinolinic acids

The close chemical relationship among these stmctural entities, as well as the uniqueness of (1) and (2), have been evident from the time of the earhest stmctural studies. Permanganate oxidation of (1) (2) produces 2,3-pyridinedicarboxyhc acid (quinolinic acid [89-00-9]) (3), whereas similar treatment of (2) (3) yields a mixture of 3,4-pyridinedicarboxyhc acid (cinchomeronic acid [490-11 -9]) (4) and phthaUc acid. 

Oxidation. The synthesis of quinolinic acid and its subsequent decarboxylation to nicotinic acid [59-67-6] (7) has been accompHshed direcdy in 79% yield using a nitric—sulfuric acid mixture above 220°C (25). A wide variety of oxidants have been used in the preparation of quinoline N-oxide. This substrate has proved to be useful in the preparation of 2-chloroquinoline [612-62-4] and 4-chloroquinoline [611 -35-8] using sulfuryl chloride (26). The oxidized nitrogen is readily reduced with DMSO (27) (see Amine oxides). 

Owing to poor volatihty, derivatization of nicotinic acid and nicotinamide are important techniques in the gc analysis of these substances. For example, a gc procedure has been reported for nicotinamide using a flame ionisation detector at detection limits of - 0.2 fig (58). The nonvolatile amide was converted to the nitrile by reaction with heptafluorobutryic anhydride (56). For a related molecule, quinolinic acid, fmol detection limits were claimed for a gc procedure using either packed or capillary columns after derivatization to its hexafluoroisopropyl ester (58). 

The kynurenine pathway metabolites are kynurenine, kynurenic acid, xahthurenic acid, 3-hydroxykynurenine, anthranilic acid and quinolinic acid. The more important are kynurenine (Kyn) and 3-hydroxykynurenine (30HKyn) (Fig 1). 

Faced with the inapplicability of the standard basic conditions required for the Pfitzinger condensation in the context of their study, Lackey and Stembach developed a modified protocol which allows for the formation of quinolinic acids under acidic conditions. ... 

They report that in the reaction between 5-chlorisatin 19 and 5,6-dimethoxindanone 20 under basic conditions at reflux for 16 hours, the desired quinolinic acid 22 is obtained in 38% yield with an unavoidable competing amount of the aldol product 21. However, if the same reaction is carried out using aqueous acid conditions, the quinolinic acid is obtained in a reproducible 86% yield. ... 

Carboxylic acids with labile a-methylene protons react with isatin in the presence of strong aqueous base. In the total synthesis of methoxatin, the coenzyme of methanol dehydrogenase and glucose dehydrogenase, Weinreb employs a Pfitzinger condensation of an isatin 37 and pyruvic acid as a key step to provide the 4-quinolinic acid 38 in 50% yield under the standard basic conditions. ... 

Chinolin, n. quinoline, -blau, n. quinoline blue, -gclb, n. quinoline yellow, -ium, n qmnolinium. -rot, n. quinoline red. -saure, /. quinolinic acid. 

QA/QC Control Metrics QT Prolongation Quantification of Diug Effect Quantitative PCR Quinolinic Acid Quinolones... 

Achim CL, Heyes MP, Wiley CA (1993) Quantitation of human immunodeficiency virus, immune activation factors, and quinolinic acid in AIDS brains. J Chn Invest 91(6) 2769-2775... 

Brew BJ, Corbeil J, Pemberton L, Evans L, Saito K, Penny R, Cooper DA, Heyes MP (1995) Quinolinic acid production is related to macrophage tropic isolates of HIV-1. J Neurovirol... 

Heyes MP, Brew BJ, Martin A, Price RW, Salazar AM, Sidtis JJ, Yergey JA, Mouradian MM, Sadler AE, KeUp J et al (1991) Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection relationship to clinical and nemological status. Ann Neurol 29(2) 202-209... 

Robusta coffee has undesirable flavor agents that can be masked by the addition of L-aspartyl-L-phenylalaninemethyl ester.218 The methylxanthine stimulant properties of coffee can be antagonized by spraying freshly roasted coffee beans with nicotinamide and nicotinic acid,219 quinolinic acid, or trigonelline.220... 

Schmieden V, Jezequel S, Betz H. Novel antagonists of the inhibitory glycine receptor derived from quinolinic acid compounds. Mol Pharmacol 1996 50 1200-1206. 

The biosynthesis and metabolism of nicotinic acid in disease has received little attention metabolic studies deal mainly with normal animals and man (01, R5). After a tryptophan load dose, the main catabolites in the urine are nicotinuric acid, N1-methylnicotinamide, nicotinamide, quinolinic acid, kynurenine, 6-pyridone, anthranilic acid, and 3-hydroxyanthranilic acid. These excretory products were estimated... 

Ve ani A, Wu HQ, Angelico P, Stasi MA, Samanin R. 1988. Quinolinic acid-induced seizures, but not nerve ceU death, are associated with extraceUular Ca " " decrease assessed in the hippocampus by brain dialysis. Brain Res 454(1—2) ... 

In addition to the glutamate and glycine sites on the NMDA receptor, there also exist polyamine sites which are activated by the naturally occurring polyamines spermine and spermidine. Specific divalent cation sites are also associated with the NMDA receptor, namely the voltage-dependent magnesium site and the inhibitory zinc site. In addition to the excitatory amino acids, the natural metabolite of brain tryptophan, quinolinic acid, can also act as an agonist of the NMDA receptor and may contribute to nerve cell death at high concentrations. 

NGF chemically conjugated to 0X26 20 pg/ injection i.v. injection daily 3 days + every 2 days 6x Rat quinolinic acid lesion Rescue of striatal cholinergic neurons... 

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