Allopurinol structure

By contrast, when allopurinol riboside (11.19), a metabolite of allopuri-nol and an antiparasitic agent, is administered orally to humans, the drug is incompletely absorbed. The residual fraction is then extensively metabolized by the enteric flora to produce metabolites that are absorbed [41], Bacterial metabolism proceeds by cleavage to allopurinol, a reaction that apparently occurs only in the intestine. Although the examples described pertain to different animal species, it is clear that small structural changes can elicit major differences in metabolism. 

Adachi and Oka investigated the formation of cyanide during the reaction of chlorine with 20 different pharmaceuticals containing nitrogen in their molecular structure [90]. High levels of cyanide were generated by chlorination of hexamine and losartan potassium aqueous solutions. Other precursors of cyanide included metronidazol, dacarbazine, and allopurinol. 

The structure of allopurinol, an isomer of hypoxanthine, is shown in Figure 36-7. 

RGURE 22-47 Allopurinol, an inhibitor of xanthine oxidase. Hypoxanthine is the normal substrate of xanthine oxidase. Only a slight alteration in the structure of hypoxanthine (shaded pink) yields the medically effective enzyme inhibitor allopurinol. At the active site, allopurinol is converted to oxypurinol, a strong competitive inhibitor that remains tightly bound to the reduced form of the enzyme. 

Prusiner. P. and M. Sundaralingam. 1972. Stereochemistry of nucleic acids and their constituents XXIX. Crystal and molecular structure of allopurinol, a potent inhibitor of xanthine oxid ste Cryst. 

The drug allopurinol, which is an inhibitor of xanthine oxidase, effectively treats gout. Allopurinol is structurally similar to hypoxan-thine, except that the 5-membered ring has the positions of the carbon and nitrogens reversed. 

An x-ray study of allopurinol (53) indicates that it exists in the 1H form. It is apparent that hydrogen bonding patterns in the crystal lattice may be responsible for the preferred protonation site in the solid state. Intramolecular N(l)-H-N(7) and N(5)-H-0(4) contacts for allopurinol and N(2)-H-0(4) contacts for allopurinol cation are observed. The crystal structure of the methyl mercury complex (56) indicated that N-l and N-5 are respective coordination sites. Similar structures have been proposed for allopurinol copper complexes <87ZN(B)195>. 

The UV spectra of isomeric pairs of pyrazolo[3,4-d]pyrimidine-4,6-diones and pyrazolo[4,3-<7]pyrimidine-5,7 diones show that the isomers with a [4,3-d] ring fusion absorb at longer wavelengths (red shift) compared to the [3,4-d] isomers <82IJC(B)585>. The />-quinonoid structure of the pyrimidine moiety in compounds (74) and (75) causes a bathochromic shift of 20-25 nm, relative to compounds (53) and (76). The close values of 2max for 7-methyl (77 R = Me) and 2,7-dimethyl allopurinol (74) suggest that the former is present in aqueous solutions as the A(2)-H tautomer <79JCS(Pl)2795>. 

Methylmercury complexes of allopurinol (56) and l-methylpyrazolo[3,4-from aqueous solutions and characterized <87ICA181>. Copper complexes of allopurinol have also been prepared by reaction with copper salts and their structures were elucidated by x-ray crystal structural analysis <87ZN(B)195>. 

The structure of 5- and 6-nitroindazole derivatives - analogs of the biological active allopurinole - was established with the aid of spectral methods including mass spectrometry (Table 3.79) [680, 1339],... 

Changed inhibitor. Xanthine oxidase treated wdth allopurinol results in the formation of a new compound that is an extremely potent inhibitor of the enzyme. Propose a structure for this compound. 

Allopurinol, a structural analogue of hypoxanthine, is a competitive inhibitor as well as a substrate for xanthine oxidase ... 

Allopurinol inhibits the formation of xanthine and of uric acid, catalyzed by xanthine oxidase, and is itself transformed into alloxanthine by the enzyme. Alloxanthine bears the same structural relationship to xanthine that allopurinol does to hypoxanthine ... 

Allopurinol, a close structural analog of hypoxanthine, prevents the oxidative conversion of the latter to uric acid and has become one of the most effective agents in the treatment of gout (Figure 19). 

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