Pyrimidopyrimidines

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... 

Yet another cytotoxic agent that lacks the glutamate side chain illustrates the breadth of the SAR in this series. It is of note that the three nitrogen atoms in the fused six-membered ring system are disposed so as to form a pyridopyrazine rather than a pyrimidopyrimidine, as in piritrexim. The observation that this agent also inhibits tubulin may play an additional role in its activity. Nucleophylic aromatic... 

The synthesis of pyrimidopyrimidines, pyrimidopyridazines and pteridines is illustrated in Scheme 31. Full details are given in the appropriate chapters of CHEC and CHEC-II. In addition to the syntheses that resemble those of quinazolines from anthranilic acid, the high reactivity of the... 

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)... 

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>. 

Thirteen diazinodiazines without bridged heteroatom are theoretically possible. All of these have been reported in the literature. There are (i) four pyridazinopyridazines, namely pyridazino-[4,3-c]pyridazine (A), pyridazino[3,4-c]pyridazine (B), pyridazino[4,5-c]pyridazine (C), and pyridazino[4,5-[Pg.738]

A lot of information about the structure, reactivity, and the best synthetic approaches for pyrimidopyrimidines has been described in CHEC-I. Additionally, some new methods of preparation of pyrimidopyrimidines have been reported in reviews on the synthesis of fused pyrimidines by Delia and Warner starting material in heterocyclic synthesis by Wamhoff, Dzenis, and Hirota <92AHC(55)129>. Pyrimidopyrimidines are especially interesting as structural analogues of natural compounds. 

The most common synthetic approaches to both types of pyrimidopyrimidine have been described in CHEC-I and in review articles by Delia . In addition some new strategies in the preparation of pyrimido[4,5-rf]pyrimidines have been developed in the last few years. A new approach is the aza-Wittig-type reaction of iminophosphoranes of 5-aminouracils with aromatic isocyanates which leads to functionalized pyrimido[4,5-rf]pyrimidines. Ethyl 1,3-dimethyl-6-(triphenylphosphoranylideneamino)-uracil-5-carboxylate (105) reacts with isocyanates via adduct (106a) intermediates to afford 7-ethoxypyrimido[4,5-. 

Several dozen patents have been granted for work in the pyrimidopyrimidine series. Most of them have been reported in the review by Delia and Warner pyrimidine analogues of folic acid (111) have been prepared and screened for antitumor activity... 

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. 

Pyrimido[4,5-inorganic bases. Reaction of the pyrimidopyrimidine (125) with ethylamine or methylamine in a sealed tube at 100 °C gives the ring cleaved product (126) (74JCS(P1)1812). 4-Methylthiopyrimido[4,5-with sodium carbonate at 20 °C to give the pyrimidine (128) (60JA6058). 

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... 

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. 

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