- Method for treating benign prostate hyperplasia
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A method of treating and/or preventing renal dysfunction in a patient, such as renal colic or contrast nephropathy by administering to a patient, a compound of the formula: is described herein. Administration of dyphylline in a sustained release oral dosage form is preferred.
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- Method of kidney treatment
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A method of treating and/or preventing renal dysfunction in a patient, such as renal colic or contrast nephropathy by administering to a patient, a compound of the formula: is described herein. Administration of dyphylline in a sustained release oral dosage form is preferred.
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- Synthesis of new 7-alkylated theophyllines by chemical modification of dyphylline
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Acetylation of 7-(2,3-dihydroxyprop-1-yl)theophylline (1) afforded the di-O-acetyl derivative 2. Reaction of 1 with acetone and benzaldehyde gave the 1,3-dioxolane derivatives 4 and 5, respectively. Periodate oxidation of 1 gave theophylline-7-acetaldehyde (6). Treatment of 6 with hydroxylamine hydrochloride, thiosemicarbazide and benzoylhydrazine afforded the corresponding oxime 9, thiosemicarbazone 10 and benzoylhydrazone 11. Treatment of 10 and 11 with boiling acetic anhydride afforded the respective 1,3,4-thiadiazoline 12 and oxadiazoline 13. Condensation of 6 with dimedone followed by boiling with dilute hydrochloric acid afforded the xanthene derivative 15.
- El Ashry, El Sayed H.,Rashed, Nagwa,Awad, Laila F.,Abdel-Rahman, Adel A. H.,Rasheed, Hanna A.
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p. 440 - 450
(2007/10/03)
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- Potentiation of cADPR-induced Ca2+-release by methylxanthine analogues
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Caffeine and other methylxanthines are known to induce Ca2+-release from intracellular stores via the ryanodine receptor. In the present work, a range of caffeine analogues, in which methyl groups at the 1 and 7 positions were replaced with alkyl chains containing different functional groups (oxo, hydroxyl, propargyl, ester, and acids), were synthesized. These compounds were then screened for their ability to potentiate Ca2+-release induced by cADPR (an endogenous modulator of ryanodine receptors) in sea urchin egg homogenates. Two of the synthesized methylxanthines, 1,3-dimethyl-7-(7- hydroxyoctyl)xanthine (37) and 3-methyl-7-(7-oxooctyl)-1-propargylxanthine (66), were shown to be more potent than caffeine in potentiating cADPR- induced Ca2+-release, while 1,3-dimethyl-7-(5-ethylcarboxypentyl)xanthine (14) was shown to be more efficacious. The development of new methylxanthine analogues may lead to a better understanding of ryanodine receptor function and could possibly provide novel therapeutic agents.
- Cavallaro, Rosaria A.,Filocamo, Luigi,Galuppi, Annamaria,Galione, Antony,Brufani, Mario,Genazzani, Armando A.
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p. 2527 - 2534
(2007/10/03)
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- Metabolism and pharmacokinetics of etofylline clofibrate, a new hypolipidaemic agent
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Upon investigations on metabolism and pharmacokinetics of 1-(theophyllin-7-yl)-ethyl-2-[2-(p-chlorophenoxy)-2-methyl-propionate] (etofylline clofibrate, ML 1024, Duolip) is reported. As can be seen from in vivo tests in rats and dogs ML 1024 is cleaved to the metabolites clofibric acid and etofylline. This could be further demonstrated in vitro by incubation with lipases and human serum. The phrmacokinetic parameters of the metabolites after oral application of 2 capsules Duolip, corresponding to 500 mg etofylline clofibrate, were evaluated in 7 healthy volunteers. The serum fluctuations of the main metabolites could be adapted to an open two-compartment model (clofibric acid) and to a one-compartment model (etofylline). The following mean values were found: the invasion half-life is 1 h 4 min for clofibric acid and 1 h 52 min for etofylline. The maximum concentration after approximately 4 h is 22.75 μg/ml for clofibric acid and 6.57 μg/ml for etofylline. The elimination half-life is 12.12 h for clofibric and 4.33 h for etofylline. Via urine 20 mg clofibric acid and 15.7 mg etofylline were excreted within 8 hr. The elimination process after 8 h is not yet terminated.
- Luecker,Wetzelsberger,Erking,Donike
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p. 2045 - 2053
(2007/10/02)
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