3- -1,1 -dimethylure

A novel approach to purine synthesis involves the use of ADC compounds as a source of one nitrogen atom in the five-membered ring.148 150 Treatment of 6-amino-l,3-dimethyluracil (94, R = H) with DEAZD gives the 5-substitution product (95, R = H). The N—N bond is cleaved by Raney nickel or formic acid, and ring closure to 1,3-dimethyluric acid is simply effected by heating.148 Whether the initial adduct is formed by a substitution... 

Analogous photoadditions have been observed on irradiation of pyrimidine and purine bases in ethers and amines. Irradiation of 1,3-dimethylur-acil (314) in tetrahydrofuran leads to the formation of 5- and 6-(tetrahydro-furan-2-yl)-5,6-dihydrouracils 315 and 316.261 Similarly, solvent adducts arising by way of initial hydrogen abstraction have been obtained on irradiation of pyrazine derivatives in diethyl ether or tetrahydrofuran.262 The... 

MefaboZ/sm/Excref/on-Xanthines are biotransformed in the liver (85% to 90%) to 1, 3-dimethyluric acid, 3-methylxanthine and 1-methyluric acid 3-methylxanthine accumulates in concentrations approximately 25% of those of theophylline. 

Dimethyluric Acid. — The reduction to 1.3-dimethyl-puron takes place very slowly in a 75% sulphuric acid solution. The molecular rearrangement to isopuron is also very slow. 

Dimethyluric Acid gives similarly a 3.9-dimethylpuron which, if heated in a 10% sodium-hydrate solution, smoothly rearranges itself to form the iso-compound. The electrolytical effect is hence a normal one ... 

Dimethyluric Acid gives correspondingly a 7.9-dimethyl-puron. 

U), 1-methylxanthine (IX) and 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1,7-dimethylurate (17U) levels in urine collected at least for 8 hours post dosing (Campbell et al. 1987 Rostami-Hodjegan et al. 1996). 

Disposition in the Body. Rapidly absorbed after oral administration bioavailability almost 100%. Metabolic reactions include V-demethylation and oxidation to uric acid derivatives. About 85% of a dose is excreted in the urine in 48 hours with up to 40% of the dose as 1-methyluric acid, 10 to 15% as 1-methylxanthine and up to 35% as 5-acetylamino-6-formylamino-3-methyluracil and 5-acetylamino-6-amino-3-methyluracil other metabolites excreted in the urine include theophylline, 1,7-dimethylxanthine (paraxanthine), 7-methylxanthine, and 1,3-dimethyluric acid. Less than 10% is excreted in the urine as unchanged drug. The extent of V-acetylation is genetically determined. Caffeine, theophylline, theobromine, and paraxanthine are found in plasma from dietary sources especially coffee, tea and cocoa. An average cup of coffee or tea contains approximately 100 mg of caffeine. 

Disposition in the Body. Readily absorbed after oral administration of aminophylline less rapidly absorbed when given as theophylline irregularly absorbed after rectal administration. Rapidly and widely distributed throughout the tissues. Metabolised by V-demethylation to form 3-methylxanthine (which is active but less potent than theophylline), 1,3-dimethyluric acid, and 1-methyluric acid. In adults, about 13% of a dose is excreted in the urine in 24 hours as unchanged drug, with about 15% as... 

Dimethylthienylmandeloyloxypyrrolidinium bromide, 653 Dimethylthiophosphoric acid, 717 Dimethyltrifluoromethylphenothiazinylpropylamine, 626 Dimethyltryptamine, 554 Dimethyltryptamine hydrochloride, 554 Dimethyltubocurarine iodide. 111 Dimethyluric acid, 421, 1012 1,3-Dimethylxanthine, 1011... 

Theophylline 7-oxide 1,3-Dimethyluric acid Heat 66LA(691)142... 

Uric acid and 1,7-dimethyluric acid were similarly produced from 2-hydroxyimidazoles (imidazolin-2-ones) by reaction with potassium cyanate (Scheme 143) (62JOC4633). 

The synthetic potential of a simple method for the direct introduction of nitrogen into the 5-position of the pyrimidine ring is illustrated by the synthesis of 1,3-dimethyluric acid (15) from 1,3-dimethyluracil-6-amine by reaction with diethyl azodicarboxylate, reduction to 5-[(ethoxycarbonyl)amino]-l,3-dimethyluracil-6-amine, and thermal ring closure. "... 

Serum of uraemic patients must not be examined in the Seralyzer, since the metabolite of 1,3-dimethyluric acid simulates a high theophylline concentration (SI 16, SI32, SI38). In a normal patient the 1,3-dimethyluric acid con-... 

Fig. 11.2. Separation of some xanthine derivatives and urinary metabolites Column uBondapak C18 (300x4 mm ID), mobile phase acetonitrile - 0.1 M disodium hydrogen phosphate and 0.1 M sodium dihydrogen phosphate in water (2 38), flow rate 1.5 ml/min, detection UV 254 nm. Peaks 1, uric acid 2, creatinine 3, 1-methyluric acid, 3-methyluric acid and 7-methyluric acid 4, xanthine 5, 7-methylxanthine 6, 1,3-dimethyluric acid 7, 3-methyl-xanthine 8, 1-methylxanthine 9, theobromine 10, 8-chlorotheophyl1ine 11, theophylline and 1,7-dimethylxanthine (paraxanthine) 12, dyphylline 13, caffeine, (reproduced with permission from ref. 80, by courtesy of Clinical Chemistry)...

Precolumn Lichrosorb RP2 10 pm (40x2.1 mm ID), column Ultrasphere ODS 5 pm (250x4.6 mm ID), mobile phase gradient with solvent A 0.01 M sodium acetate and 0.005 M tetrabutylammonium hydrogen sulfate in water (pH 4.9), solvent B same salt concentrations in 50% methanol (pH 4.8). Gradient 0-7.5 min 0 B, 7.5-15 min 0-T5% B, 15-25 min 15-30% B, 25-33 min 30-32% B, 33-38 min 32-45% B and 38-41 min 45-0% 6. Detection UV 280 nm. Peaks 1, xanthine 2, uric acid 3, 3-methyluric acid 4, 7-methyl xanthine 5, 3-methyl xanthine 6, 1-methylxanthine 7, theobromine 8, 3,7-dimethyl uric acid 9, 7-methyluric acid 10, 1-methyluric acid 11, 1,3-dimethyluric acid 12, 1,7-dimethyl xanthine 13, theophylline 14, e-hydroxyethyltheophylline (internal standard) 15, 1,7-dimethyluric acid 16, 1,3,7-trimethyluric acid 17, caffeine, (reproduced with permission from ref. 192, by the courtesy of Journal Chromatographic Science)... 

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