Theophylline 7-methyl

D - Ribofuranosylpy rimidine - 2 -one, 7 - (methyl 2 - acetamido -6-0- acetyl -2,3,4-trideoxy-j3-D-ery /Iro-hex-2-enopyranosid-4-yl)theophylline, 7-(methyl 2-acetamido - 6 - O - acetyl - 2,3,4 - trideoxy - a - D - threo - hex-2-enopyranosid-4-y 1 )theo-phylline, 5,6-dimethyl-l-(0 -D-ribofuranosyl)benzimidazole and 5-amino-l-/3-D-ribofuranosylimidazole-4-carboxamide (and its 5-phosphate). 

Theobromine, 6-thio-methylation, 5, 535 Theophylline alkylation, 5, 532 C-alkylation, 5, 537... 

Theophylline, 7-alkoxy-8-methyl-reactions, 5, 554 Theophylline, 8-alkyl-synthesis, 5, 573 Theophylline, 8-aryl-... 

Theophylline, 9-aryl-synthesis, 5, 576 Theophylline, 8-arylamino-synthesis, 5, 576 Theophylline, 9-benzyl-rearrangement, 5, 534 Theophylline, 8-chloro-reduction, 5, 541 Theophylline, 6-deoxy-reduction, 5, 541 Theophylline, 8-dimethylamino-synthesis, 5, 580 Theophylline, 8-methyl-synthesis, 5, 591 Theophylline, 8-methylthio-synthesis, 5, 578 Theophylline, 8-nitro-synthesis, 5, 538 Theophylline, 7-phenyl-synthesis, 5, 581 Theophylline, 8-phenyl-7-oxide... 

C9H13NO 104-63-2) see Indeloxacine Phenmetrazine 7-(2-benzylaminoethyl)theophylline (C15H19N5O2 22680-61-1) see Fenetylline Theodrenaline benzyl [(2R,35)-3-amino-2-hydroxy-4-phenylbutyl](2-methylpropyl)carbamate monohydrochloride (C22H3[C1N20j 160232-11-1) see Amprenavir 2-benzylamino-l-(4-methoxyphenyl)propane (C17H21NO 43229-65-8) see Fenoterol Formoterol benzyl [3-[(2-aminophenyl)carbamoyl]propyl]methyl> carbamate... 

Figure 33-8. Caffeine, a trimethyixanthine. The di-methylxanthines theobromine and theophylline are similar but lack the methyl group at N-1 and at N-7, respectively.

Much research has centered on identifying the source of the purine ring in caffeine. Two possible sources are likely methylated nucleotides in the nucleotide pool and methylated nucleotides in nucleic acids. Extensive experimental work by Suzuki and Takahashi27-30 proposes a scheme whereby caffeine is synthesized from methylated purines in the nucleotide pool via 7-methylxanthosine and theobromine. Information relating to the formation of 7-methylxanthine from nucleotides in the nucleotide pool is sparse. They also provide data that demonstrate that theophylline is synthesized from 1-methyladenylic acid through 1-methylxanthine as postulated by Ogutuga and Northcote.31... 

Foods derived from cocoa beans have been consumed by humans since at least 460 to 480 AD. The source of cocoa beans, the species Theobroma, contains a variety of biologically active components. These include the purine alkaloids theobromine, caffeine, and theophylline. Structurally, they are methylated xanthines and, thus, are often referred to as methylxanthines. Theobromine (3, 7-dimethylxanthine) is the predominant purine alkaloid in cocoa and chocolate. Caffeine (1, 3, 7-trimethylxanthine), the major purine alkaloid found in coffee and tea, is found in cocoa and chocolate at about one eighth the concentration of theobromine. Only trace amounts of theophylline (1, 3-dimethylxanthine) are detected in cocoa and chocolate products. 

Ci8H23Ns07 7-(Methyl 2-acetamido-6-0-acetyl-2,3,4-trideoxy-a-D-threo-hex-2-enopyranosid-4-yl)theophylline (HPTHOP20)174... 

In the case of the methylated xanthines, particularly theophylline, theobromine and caffeine, the preponderance of data on the metabolism of these compounds in man suggests that a methylated uric acid is the principal product. However, the data presented earlier proposes at best a 77 per cent accounting of the methylated xanthine administered. The question can be raised as to whether the final products observed upon electrochemical oxidation of these compounds aids these studies. Very recently studies of metabolism of caffeine have revealed that 3,6,8-trimethylallantoin is a metabolite of caffeine 48>. This methylated allantoin is, of course, a major product observed electrochemically. The mechanism developed for the electrochemical oxidation seems to nicely rationalize the observed products and electrochemical behavior. The mechanism of biological oxidation could well be very similar, although insufficient work has yet been performed to come to any definite conclusions. There is however, one major difference between the electrochemical and biological reactions which is concerned with the fact that in the former situation no demethylation occurs whereas in the latter systems considerable demethylation appears to take place. 

An interesting pair of compounds is caffeine and theophylline [97] these compounds are relatively polar compounds with different functional groups (tertiary and secondary amine). In a few cases, more appropriate comparisons have been made such as between androstenedione/testoster-one and methyl benzoate/anisole these compounds are expected to be different in Snyder interaction groups. 

In attempts to prepare methylated xanthine analogues with greater therapeutic effectiveness as diuretic and cardiac drugs than theophylline (LXIV) and theobromine (LXV), it was found that some of the intermediate 6-aminouracils (LXVI) showed considerable activity as oral diuretics in experimental animals... 

As with adults, the primary organ responsible for drug metabolism in children is the liver. Although the cytochrome P450 system is fully developed at birth, it functions more slowly than in adults. Phase I oxidation reactions and demethylation enzyme systems are significantly reduced at birth. However, the reductive enzyme systems approach adult levels and the methylation pathways are enhanced at birth. This often contributes to the production of different metabolites in newborns from those in adults. For example, newborns metabolize approximately 30% of theophylline to caffeine rather than to uric acid derivatives, as occurs in adults. While most phase I enzymes have reached adult levels by 6 months of age, alcohol dehydrogenase activity appears around 2 months of age and approaches adult levels only by age 5 years. 

Most drugs are administered to infants and children for the same therapeutic indications as for adults. However, a few drugs have found unique uses in children. Among these are theophylline and caffeine, which are used to treat apnea of prematurity indomethacin, which closes a patent ductus arteriosus and prostaglandin Ej, which maintains the patency of the ductus arteriosus. Paradoxically, drugs such as phenobarbital, which have a sedating action on adults, may produce hyperactivity in children, and some adult stimulant drugs, such as methyl-phenidate, are used to treat children with hyperactivity. 

The intracellular signal therefore persists only as long as the hormone receptor remains occupied by epinephrine. Methyl xanthines such as caffeine and theophylline (a component of tea) inhibit the phosphodiesterase, increasing the half-life of cAMP and thereby potentiating agents that act by stimulating adenylyl cyclase. 

Conversion of L-fucosyl- and 3 -0-methyl-D-glycosyl-purines into nucleosides of two naturally occurring, rare sugars, 6-deoxy-L-talose and 3-O-methyl-D-mannose, could be achieved57 by stereospecific reduction at C-2 of 7-(6-deoxy-3,4-0-isopropylidene-/ -L-h/xo-hexopyranosyl-2-ulose)theophylline (35a) and 7-(4,6-0-benzylidene-3-0-methyl-/ -D-orobtno-hexopyranosyI-2-ulose)theophylline (8). Treatment of 35a and 8 with sodium borohydride in ethanol afforded the expected 7-(6-deoxy-3,4-0-isopropylidene-/ -L-talopyranosyI)theophylline (84) and 7-(4,6-... 

ATP, ADP, and adenosine are among the purines that are present in some synapses and activate a variety of receptors. Adenosine receptors are blocked specifically by methylated xanthines such as caffeine (Fig. 25-18) and theophylline.808 80813 A drug almost 105 times as potent as theophylline is l,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine.809 Adenosine receptors, which are present in large numbers in the hippocampus,149 form functional complexes with metabotropic glutamate receptors.678 Adenosine... 

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