Hypoxanthine derivatives

Ara-A-5 -monophosphate [29984-33-6] (ara-AMP), C2QH24N OyP, is more water-soluble than ara-A, and therefore can be used in higher dosage during the first hours of treatment of viral infections. Ara-AMP has been shown to decrease virion-associated DNA polymerase concentrations in ground squirrels carrying ground squirrel hepatitis vims. The hypoxanthine derivative, ara-HxMP [54656-49-4] (24) is more water-soluble, appears to have a similar antiviral spectmm to ara-A, and is considerably less toxic (48). 

Reaction of 6-halopurines with Michael acceptors under Heck conditions gives N- -substituted hypoxanthine derivatives <00CCC797>. Reactions of a series of 1-aminobenzimidazoles and l-amino-3-methylbenzimidazolium chlorides with 2,4-pentanediones afford pyridazino[l,6-a]benzimidazoles and 2-pyrazolylanilines, the product ratio depending on conditions and on the electronic character of the substituents at the benzene moiety <00BMC37>. Cyclization reactions of adenine derivative 75 with different amines or hydrazine afford tricyclic polyaza compounds 76 <00CCC1109>. 

The predominant binding site in 9-substituted 6-oxopurines (guanine and hypoxanthine derivatives) is the N7 atom of the base (Figure 6). The prevailing keto tautomer requires proton at N1 even in mildly acidic conditions, which efficiently prevents platination of the N1 site [7]. Under neutral and basic conditions competition of Pt(II) between the N1 and N7 sites has been reported. Attachment of Pt(II) to the N7 atom acidifies the N1H proton and facilitates coordination of additional platinum ions to both N1 and N3 [7]. In N7,N9-blocked 6-oxopurines, the N1 site is the major coordination site [7,24],... 

Purine catabolism to uric acid and salvage of the poime bases hypoxanthine (derived from adenosine) and guanine are shown in 1-18-5. 

Sakore TD, Sobell HM (1969) Crystal and molecular structure of a hydrogen-bonded complex containing adenine and hypoxanthine derivatives 9-ethyl-8-bromoadenine 9-eth-yl-8-bromohypoxanthine. J Mol Biol 43 77-87... 

Buncel et al. [86] in a stepwise trimercuration of the hypoxanthine derivative inosine (see Figure 6.36) proposed a mechanism that takes account of the difference in reactivity of the available mercuration sites K > N > C. Interestingly, they had already proposed the existence of an yUdene (carbene) structure for the dimercurated compound. 

Useful precursors for the preparation of substituted hypoxanthine derivatives are alkyl 4(5)-aminoimidazole-5(4)-carboxylates. Thus, reaction of ethyl 4-amino-l-arylimida7ole-5-carb-oxylates with thioamides in the presence of a catalytic amount of formic acid gives 2-substituted 7-arylhypoxanthines, e.g. formation of l. °... 

A novel approach to adenine and hypoxanthine derivatives involves a high-temperature intramolecular cyclization of 4(5)-substituted-amino-5(4)-unsubstituted-imidazole intermediates. For example, reaction of 1,2-dimethylimidazol-5-amine with (ethoxymethylene)urethane gives the Af -ethoxycarbonyl-jV -(imidazol-5-yl)formimidamide which under thermal cyclization is rapidly transformed into 8,9-dimethylhypoxanthine (3). 

A number of hypoxanthine derivatives have resulted from rearrangement of 7-oxoimidazo-[4,5-rfl[l,3]oxazines with an amine hydrochloride in a mixture of Af,A -dimethylcyclohexylamine and phosphorus pentoxide in which the overall effect is the replacement of the ring oxygen by nitrogen, e.g. formation of 9. ... 

A study of hypoxanthine derivatives and uracil derivatives has shown that no selective hydrogen bonding occurs between these molecules in solution. (Kyogoku et al., 1969). 

An essential role for the N -amino group of adenosine or adenylic acid was demonstrated when it was found that the corresponding hypoxanthine derivatives, inosine... 

Mutations can also be caused chennically, and nitrous acid is one of the most potent chemical mutagens. One explanation that has been suggested for the mutagenic effect of nitrous acid is the deanfination reactions that it causes with purines and pyrimidines bearing amino groups. When, for example, an adenine-containing nucleotide is treated with nitrous add, it is converted to a hypoxanthine derivative ... 

Adenosine deaminase converts adenosine and deoxyadenosine to the corresponding hypoxanthine derivatives (25). The enzyme is widely distributed and has been partially purified (25) from calf intestinal mucosa (26-28). 

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