Theophylline derivative

A somewhat more complex theophylline derivative includes both the purinone nucleus and a piperazine side chain more commonly associated with HI antihistaminic compounds. The starting epoxide, 66, is available from treatment of the anion of purinone 65 with epichlorohydrin. Alkylation of the epoxide with monosubstituted piperazine derivative 67, leads to tazifylline (68) [11]. 

Chlorination of theophylline derivatives 150 with POCI3 and PCI5 furnishes the tricyclic chlorides 151 (Equation 6) <1998CHE488, 2004JME2659>. Other examples of application of this chlorination method have been reported C1999PHA876, 2004JME1329, 2005BML3778>. 

Nitrene intermediates are implicated in the formation of the pyrrole (64) from an azirinyl aldehyde and (65).67 Treatment of the nitrosouracil (66) with benzyl idene-ylides affords the corresponding theophylline derivatives.68 Hydrazonic halides and keto-ylides initially give betaines (67), which ring-close to (68) on heating.69... 

The unpleasant sedative CNS effect of most antihistamines, combined with their slight anticholinergic activity, is exploited for the prevention of motion sickness. Diphenhydramine (2.5), in the form of an 8-chlorotheophylline salt (dimenhydrinate, 4.148), is widely used for this purpose. The theophylline derivative was originally added to counteract the drowsiness produced by diphenhydramine, since it is a central excitant related to caffeine. 

In 0.1 M methanolic sodium hydroxide, the 6-chloropurine ketonu-cleoside 41b was cleaved after 30 min, whereas the theophylline derivative 41a was unaffected.26,27 The stability of the theophylline ketonu-cleoside 41a maybe explained by the establishment of a hydrogen bond between the 4 -gem-diol system (hydrate form of 41a) and the 2-keto group of theophylline. The assigned 4Ct (l) conformation would facilitate this bonding, whereas it could not occur with the 6-chloropurine derivative regardless of its conformation.27... 

Xanthine derivatives are a group of chemically similar compounds that exert a variety of pharmacologic effects. Common xanthine derivatives include theophylline, caffeine, and theobromine (Fig. 26-2) these compounds are frequently found in various foods and beverages (tea, coffee, soft drinks). Theophylline and several theophylline derivatives are also administered therapeutically to produce bronchodilation in asthma and other forms of reversible airway obstruction (bronchitis, emphysema).65,79 Theophylline and caffeine are also potent CNS stimulants, and some of the more common side effects of these drugs are related to this CNS excitation (see Adverse Side Effects, later in this chapter). 

The reaction of polymer 31 with the sodium salt of adenine affords stereoregular polyMAOA and the reaction of 31 with theophylline the theophylline derivative 32. Stereoregular polyMAOU was obtained by the reaction of 3/ with the sodium salt of 4-ethoxy-2-pyrimidone followed by add hydrolysis of the resulting polymer 33. The results of the polymer reactions are listed in Table 3. 

This type of precursor has been widely used for the synthesis of different 8-substituted theophyllines.Thus, treatment of 5-(aryldiazenyl)-l,3-dimethyluracil-6-amines with ethyl propiolate gives the corresponding Michael-type adducts, 5-(aryldiazenyl)-l, 3-dimethyl-6-[(2-cthoxycarbonylvinyl)amiiio]uiacils, which on treatment with a mixture of hydrochloric and acetic acid result in acid-catalyzed rearrangement to give the 8-(anilinomethyl)theophylline derivatives, c.g. the sequence 8 9 10. 

Several modified-release formulations are available. Maximum serum concentrations occur at 1-3 hours with most of the standard formulations and at up to 6 hours with modified-release formulations. In aminophyl-line, the most widely used theophylline derivative, theophylline is combined with ethylenediamine to enhance its solubility. Since ethylenediamine is therapeutically inert, all the effects of aminophyUine, except for allergic reactions, are considered to stem from the theophyUine component. 

Pyrldlum phenazopyridine. pyrldofylllne [inn] (theophyllinylethyl sulphate) is a theophylline derivative, and is a RESPIRATORY aiid cns stimulant. It is also a coronary VASODILATOR and BRONCHODILATOR that has been used in ANTIASTHMATIC and antibronchitic treatment, pyrldoglutethlmlde rogletimide. pyridostigmine bromide [ban. inn, jan, usan]... 

Treatment of 6-amino-5-arylazo-1,3-dimethyluracils (e.g. 271) with ethyl propiolate gives the Michael-type adducts (272), which, on further treatment with a mixture of hydrochloric acid and acetic acid, undergo acid-catalysed rearrangement and cyclisation to give the 8-anilinomethyl-theophylline derivative (273) When... 

A new synthesis of trans-4-amino-l-hydroxy-2-methylbut-2-ene, an intermediate in the preparation of trans-zeatin (see Vol. 4 of these Reports) has been developed.A large number of 7-substituted theophylline derivatives (23a—i) have been synthesized by conventional steps as a result of observed pharmacological activity of this type of compound. For example, various 7-amino-... 

It is a theophylline derivative. Its aetions and uses are similar to those of aminophylline. It is foimd to be better tolerated both orally and intravenously. 

Figure 12 Imprinting of a theophylline derivative immobilized on silica. The template (a carboxypropyl-derivative of theophylline) was immobilized on porous and spherical amino-functionalized silica gel via formation of an amide bond. This construct is then imprinted with traditional imprinting monomers (TFMAA and DVB). Following polymerization, the composite material is treated with HF to dissolve and remove the silica gel, leaving spherical porous MIP particles which mirror the original silica in size, shape, and porosity.

Thiazolo-[2,3-/]- and -[3,2>e]-purines [CsNS-CsNa-CiNg].—thiazole ring can be annelated to the purine ring system by standard procedures to give, e.g., compounds (105) obtained from the corresponding theophylline derivatives. ... 

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