Azapurines

Azapurine, 6-amino-synthesis, 5, 726-727 8-Azapurine, 1-deaza-synthesis, 5, 887 8-Azapurine, 3-deaza-synthesis, 5, 887 8-Azapurine, 6-methylthio-degradation, 5, 721 8-Azapurines nomenclature, 1, 36... 

The fusion name l//-triazolo[4,5-d]pyrimidine for (140) is preferred by practitioners in the field and appears in CA indexes. On the other hand, the nonspecialist, who may well be uncertain about his command of fusion nomenclature, might more easily grasp the replacement name l//-l,2,3,4,6-pentaazaindene. (This is an appropriate place to emphasize that, by lUPAC rules, replacement names are to be based only on a completely carbocyclic parent. Notwithstanding the attractive simplicity of 8-azapurine for the example at hand, it has no sanction see, however. Section 1.02.3.2. The purpose of this avoidance is to forestall a multiplicity of names for systems containing several hetero atoms.)... 

Covalent hydration has been demonstrated in the following families of compounds 1,6-naphthyridines, quinazolines, quinazoline. 3-oxides, four families of l,3,x-triazanapththalenes, both l,4,x-triazanaphthalenes, pteridines and some other tetraazanaphthalenes, and 8-azapurines these compounds are discussed in that order. In general, for any particular compound (e.g. 6-hydroxypteridine) the highest ratio of the hydrated to the anhydrous species follows the order cation > neutral species > anion. In some cases, however, anion formation is possible only when the species are hydrated, e.g. pteridine cf. 21 and N-methyl-hydroxypteridines (Section III, E, 1, d). Table V in ref. 10 should be consulted for the extent of hydration in the substances discussed here. 

This does not exclude the possibility that hydration occurs too rapidly to be detected with existing apparatus. Special point is given to this conclusion by a recent survey of 8-azapurines.The abnormal... 

Hydroxy-8-azapurine was shown by rapid-reaction techniques (see Section II, E) to be anhydrous in the anion and hydrated in the neutral species. The hydration reaction has a half-time of about 0.5 second, which is too rapid for exact measurements with existing apparatus. The cation of 2-amino-8-azapurine was shown to have an anomalous value and ultraviolet spectrum, although its 6-methyl derivative is quite normal. Hydration in this case proved to be too fast to register in the rapid-reaction apparatus. 

Similar pyrimidine-to-pyridine conversions were also reported for purine and 8-azapurine with C-H active acetonitriles, ethyl acetoacetate, acetylacetone with dimedone 8-azapurine is converted into triazolotetra-hydroquinoline (Scheme 15) (73JCS(P1)1620, S(Pl)1625, S(P1)1794). 

To test whether we could accurately calculate the fold-difference of ADA inhibitory potency between purine riboside (8) and analogues of purine riboside, we selected 8-azapurine riboside (9) for our studies. Compound 9 was reported to be a 400-fold more potent ADA inhibitor relative to 8 despite differing from 8 only by the replacement of C8 with a nitrogen (Figure 8).19 The molecular reason for this enhancement in potency was not determined, but could be due either to enhanced hydration or enhanced ADA binding affinity of the hydrated species or both. To determine the reason,... 

Figure 8. Purine riboside/8-azapurine riboside and corresponding hydrates...

An alternative explanation for the 400-fold improvement in inhibitory potency exhibited by 8-azapurine riboside (9) is that the 8-aza analogue hydrates to a much larger extent than purine riboside (8). Calculation of the relative hydration free energy difference between 9-methylpurine and 8-aza-... 

Aminobenzenesulfonic acid and 3-aminobenzenesulfonyl chloride failed to react with EMME (77JMC1001). (Substituted phenylamino)meth-ylenemalonates (48) were prepared in the reaction of 2-(5-amino-2-alkoxyphenyl)-8-azapurin-6-ones and EMME at 140°C (78GEP2747199 82SZP627755). 

Similar base-induced Dimroth rearrangements have also been reported with the related iminopyrazolo[3,4-d]pyrimidines (60JA3147) and 6-imino-8-azapurines [73JCS(PI)2659]. 

A similar route to the i -triazolo[4,5-d]pyrimidine ( 8-azapurine ) ring system has been developed. This involves reaction of 4-amino-l,2,3-triazole-5-carboxamide or its ring iV-alkyl derivatives with formamide (Scheme 46). - 232-234 pyrimidone derivatives thus... 

Variation of the ring portion of acyclovir has been achieved. Compounds include monocyclic (isocytosine, triazole, imidazole), bicyclic (adenine, 8-azapurine, pyrrolo[2,3-c/]-pyrimidine, pyrazolo[3,4-[Pg.131]

MI4). The 8-azapurine analog showed some activity against HSV-1 and the tricyclic derivative exhibited a competition with ACV for binding to HSV-1 thymidine kinase (85JMC982). 

Triazole and 8-azapurine derivatives 843 were prepared by the cyclocondensation of the acyclic azide derivative 842 with cyanoacetamide, norbornadiene, and acetylene derivatives (90H1669). 

The carboacyclic nucleoside analogs considered under this section could be also considered in Section III,G as a component resulting from two bond disconnections. However, it is preferable to consider them as acyclovir analogs. The carboacyclonucleosides having purine 934 and 8-azapurine rings 935 have been prepared starting by reaction of 2-amino-... 

A -Triazolines (350) are easily converted into the corresponding 8-azapurines (351) on treatment with ethyl formate and sodium ethoxide (Equation (31)) <88S879>. When 5-amido-A -l,2,3-triazoline (352) is treated with trifluoroacetic acid, the 2-methyl-1,2,3-triazole (353) is afforded (Scheme 67) <91JCS(P1)3361>. 

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