Pyrimidopyrimidine derivatives

Hydrogen peroxide was determined with fmol detection limits by using rhodamine 6G and pyrimidopyrimidine derivatives as fluorescent enhancers. The method employing the latter reagent was applied to cola drinks [92], Sensitive... 

Benzyl-4,6-dimethyl-2//-pyrazolo[3,4-(f pyrimidine-2,4-(l H,3H) dione-l-oxide (188) affords the pyrimidopyrimidine derivative (191), most likely via the intermediates (189) and (190) (Scheme 11)... 

Characteristics of proposed CL reaction. In the preliminary study, CL intensities of several types of fluorophores were measured after mixing with only aryloxalate and without addition of hydrogen peroxide. DBP derivatives and pyrimidopyrimidine derivatives showed CL, but the CL was not observed with typical fluorophores that are frequently used in conventional PO-CL reactions such as dansyl, benzoxazole, lophine and fluorescein derivatives. Therefore, it is proposed that this CL reaction can detect DBP derivatives selectively in the presence of other fluorophores. 

Dipyridamole Is a pyrimidopyrimidine derivative with vasodllatory and antiplatelet properties, whereas cllostazol Is a quinollnone derivative, which Is a potent, orally active antiplatelet with a higher degree of selectivity than dipyridamole for PDE3. The latter drug appears to possess greater therapeutic potential. It Is rapidly absorbed following oral administration and Is extensively metabolized. Several of the metabolites also possess antiplatelet activity. (For a more In-depth discussion of these drugs, see Chapter 31.)... 

Dipyridamole is a pyrimidopyrimidine derivative with vasodilatory and antiplatelet properties (Fig. 31.17). Dipyridamole exerts its antiplatelet function by increasing cellular concentrations of cAMP via its inhibition of the degradating enzyme, cyclic nucleotide PDE3. It also blocks adenosine uptake, which acts at A2 adenosine receptors to stimulate platelet adenyl cyclase. Less common uses for this drug include inhibition of embolization from prosthetic heart valves when used in combination with warfarin (the only currently recommended use) and reduction of thrombosis in patients with thrombotic disease when used in combination with aspirin. Alone, dipyridamole has little, if any, benefit in the treatment of thrombotic conditions (102). 

Ab initio molecular orbital calculations on these systems have been confined to the 1,2,3-triazolo[4,5-d]pyrimidines (7), the so-called 8-azapurines , and references to this subject may be found in the previously mentioned review <86AHC(39)ii7>. In 1989, quantum mechanical perturbation methods have been used to study the activity of 8-azapurine nucleoside antibiotics in transcription processes <89Mi 7i3-oi>. The l,2,3-thiadiazolo[5,4-d]pyrimidine derivative (51), a rearrangement product of 8-aza-6-thioinosine, has been used in a molecular modeling study of the antitumor activity of sugar derivatives of pyrimidopyrimidines <89PNA(86)8242>. 

A novel and versatile solid-phase synthesis of pyrimido[4,5- fJpyrimidine-2,4-diones has been reported <03S1739>. The key step is the reaction of the support-bound pyrimidine with isocyanates, involving formation of a carbamate intermediate, followed by a base-catalyzed intramolecular ring closure to give the polymer-bound pyrimidopyrimidines which are used in subsequent reactions providing 1,3-disubstituted 7-amino derivatives. 

The IR spectra of pyrimidopyrimidines are extremely similar to those of the isomeric pteri-dines.106 IR spectral data for amino- and anilino-substituted pyrimido[4,5-rf]pyrimidines indicate NH absorptions in the range of 3130-3470 cm-1 (see Table 16).108,113 114 The ring vibrations for tetra-substituted derivatives are observed in the range 1550-1600 cm-1.108... 

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