6- Methylthio-9- purine

Purine, 6-methylsulfonyl-9- -D-ribofuranosyl-synthesis, 5, 597 Purine, 2-methylthio-hydrolysis, 5, 560 methylation, 5, 537 Purine, 6-methylthio-irradiation, 5, 543 Mannich reaction, 5, 536 oxidation, 5, 561 Purine, 8-methylthio-amination, 5, 542 synthesis, 5, 575... 

Purines, N-alkyl-N-phenyl-synthesis, 5, 576 Purines, alkylthio-hydrolysis, 5, 560 Mannich reaction, 5, 536 Michael addition reactions, 5, 536 Purines, S-alkylthio-hydrolysis, 5, 560 Purines, amino-alkylation, 5, 530, 551 IR spectra, 5, 518 reactions, 5, 551-553 with diazonium ions, 5, 538 reduction, 5, 541 UV spectra, 5, 517 Purines, N-amino-synthesis, 5, 595 Purines, aminohydroxy-hydrogenation, 5, 555 reactions, 5, 555 Purines, aminooxo-reactions, 5, 557 thiation, 5, 557 Purines, bromo-synthesis, 5, 557 Purines, chloro-synthesis, 5, 573 Purines, cyano-reactions, 5, 550 Purines, dialkoxy-rearrangement, 5, 558 Purines, diazoreactions, 5, 96 Purines, dioxo-alkylation, 5, 532 Purines, N-glycosyl-, 5, 536 Purines, halo-N-alkylation, 5, 529 hydrogenolysis, 5, 562 reactions, 5, 561-562, 564 with alkoxides, 5, 563 synthesis, 5, 556 Purines, hydrazino-reactions, 5, 553 Purines, hydroxyamino-reactions, 5, 556 Purines, 8-lithiotrimethylsilyl-nucleosides alkylation, 5, 537 Purines, N-methyl-magnetic circular dichroism, 5, 523 Purines, methylthio-bromination, 5, 559 Purines, nitro-reactions, 5, 550, 551 Purines, oxo-alkylation, 5, 532 amination, 5, 557 dipole moments, 5, 522 H NMR, 5, 512 pJfa, 5, 524 reactions, 5, 556-557 with diazonium ions, 5, 538 reduction, 5, 541 thiation, 5, 557 Purines, oxohydro-IR spectra, 5, 518 Purines, selenoxo-synthesis, 5, 597 Purines, thio-acylation, 5, 559 alkylation, 5, 559 Purines, thioxo-acetylation, 5, 559... 

Purine, 9-methyl-6-methylamino-synthesis, 5, 570 Purine, 3-methyl-6-methylthio-irradiation, 5, 543 synthesis, 5, 535, 595... 

Purine, l-methyl-2-methylthio-6-thioxo-l,6-dihydro-amination, 5, 560 Purine, 9-methyl-8-phenyl-dipole moments, 5, 521 Purine, 9-methyl-8-phenyl-6-thiomethyl-dipole moments, 5, 521 Purine, 6-methylsulfonyl-synthesis, 5, 597... 

Purine, 2-methylthio-6,8-diphenyl-ring transformations, 3, 308 Purine, 9-methyl-6-thiomethyl-dipole moments, 5, 521... 

Purine, 2-methylthio-6-oxo-8-thioxo-synthesis, 5, 579 Purine, 9-methyl-8-thioxo-synthesis, 5, 578... 

Mercaptopurine probably exists in a thione form (e.g., 167) since its ultraviolet spectrum is different from that of 2-(methylthio)pur-ine. Purine-2-thione and its 6-amino derivative were assigned thione structures on the basis of their infrared spectra.8-Mercapto-9-methyl- and b-mercapto-T-methjd-purine exist at least partially in thione forms, presumably 168 and 169, respectively, since their in-... 

Imidazole units have been substituted on poly(vinyl alcohol) chains to the extent of 19-51% as shown in Equation 14 (54). This reaction was run 1-5 days as a 1% solution in DMF at 85°C. Using the sequence of reactions outlined in Equation 15, 6-methylthio-purine units have been placed on the poly(vinyl alcohol) backbone (55). These polymers might be useful in treating cancer or leukemia since the parent compound, 6-mercaptopurine, is used in this way. 

Thus, 2-methylthio-4,6,7-triphenylpteridine is a mM reactive compound. It shows activity to nucleophiles at four ring carbon atoms at C-4 [Sn(AN-RORC)], at C-2 [Sn(AE)], and at C-6, as well as at C-7 (purine formation). Based on qualitative product studies and N-label incorporation studies, the order of reactivity is approximately C-4 > C-2 > C-7 > C-6. 

It is particularly interesting that 6-mercaptopurine ribonucleoside (XXI) [158] is an inhibitor of, but not a substrate for, the kinase [47] but 6-(methylthio)purine ribonucleoside (XXII) [159, 160], resulting from the... 

Although demethylation, which occurs in the liver, is normally considered to be a catabolic process, it may result in conversion of an inactive form of a drug to the active form. Thus 6-(methylthio)purine (XXXIX) is demethylated by the rat to 6-mercaptopurine [205]. This demethylation occurs in the liver micro-somes and is an oxidative process which converts the methyl group to formaldehyde [204, 207]. The 1-methyl derivative of 4-aminopyrazolo[3,4-d] pyrimidine (XLI) is demethylated slowly, but 6-mercapto-9-methylpurine (XLII) not at all [208]. The A -demethylation of puromycin (XLlIl) [209, 210], its aminonucleoside (XLIV) [211], and a number of related compounds, including V-methyladenine and V,V-dimethyladenine, occurs in the liver microsomes of rodents [212]. In the guinea-pig the rate-limiting step in the metabolism of the aminonucleoside appears to be the demethylation of the monomethyl compound, which is the major urinary metabolite [213]. The relationship of lipid solubility to microsomal metabolism [214], and the induction of these demethylases in rats by pre-treatment with various drugs have been studied [215]. 

Methylation of some form of 6-mercaptopurine in man has been established by the identification of 6-(methylsulphinyl)-8-hydroxypurine (LXV), 6-(methylthio)uric acid (LX), and 6-(methylthio)-8-hydroxy-A -glucuronide (LXVll). The oxidation of 6-(methylthio)purine to 6-(methylthio)-8-hydroxy-purine (LXVl) is mediated much more rapidly by rabbit liver aldehyde oxidase than by xanthine oxidase, and the oxidation is not inhibited by 4-hydroxy-pyrazolo [3, 4-d] pyrimidine [269], which is known to be an effective inhibitor of xanthine oxidase, and consequently, of the oxidation of 6-mercaptopurine [12,268]. 

Studies on the mechanism of action of 6-mercaptopurine are complicated by the fact that its anabolic product, thioinosinic acid, is further metabolized by oxidation to 6-thioxanthylic acid [219] and by methylation to 6-(methylthio)purine ribonucleotide [206, 296]. the effects of which could be even more important than those of thioinosinic acid itself, since the methylthio compound is about 20 times as potent as a feedback inhibitor [289]. 

A number of thiopurines (thioguanine, 6-mercaptopurine, 6-(methylthio) purine, azathioprine (6[( l-methyl-4-nitro-5-imidazolyl)thio] purine) [12],and other derivatives of 6-mercaptopurine [377]) have all been used to successfully prolong homografts, and azathioprine (Imuran) appears to be superior in its action [268]. 

Certain derivatives of 6-mercaptopurine, such as 6-(methylthio)purine, 6-mercaptopurine-3-oxide [448a], and 6-mercaptopurine ribonucleoside and its acylated derivatives apparently owe their activity to their in vivo conversion to 6-mercaptopurine [11,13]. It would appear, however, that the 9-alkyl derivatives of 6-mercaptopurine, and its arabinosyl and xylosyl derivatives, are not metabolized-except in the case of the 9-alkyI derivatives, to a limited extent to their 5-glucuronides—and that their mechanism of action is quite different from that of 6-mercaptopurine. 

Methylthio-purin reagiert mit Anilin in Gegenwart von Quecksilber(II)-chlorid zu einem Komplex, dessen Zersetzung mit Schwefclwasserstoff 6-Anilino-purin (77%) ergibt ... 

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