Thio-Purines

Standard condensation procedures have been used to prepare 7- and 9-(6 -deoxy-a-L-talofuranos l) derivatives of hypoxanthine, guanine, and 6-thio-purine, the derivatives of the last purine shov/ing marked antitumour activity. 2-Deoxy-D-ribofuranosyl chloride condensed with N-trimethylsilyl-4-carboxymethyl-5-cyanomethylimidazole in presence of stannic chloride (best catalyst tried) gave a- and... 

Chemical Name 6-[(1-methyl-4-nitroimidazol-5-yl)thio] purine... 

Seki T, Tanaka T, Nakamura Y. Genomic stmcture and multiple single-nucleotide polymorphisms (SNPs) of the thio-purine S-methyltransferase (TPMT) gene. J Hum Genet 2000 45 299-302. 

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]. 

Azathioprine Azathioprine, 6-[(l-methyl-4-nitroimidazol-5-yl)thio]purine (31.2.1), is synthesized by heteroarylation of the sulfhydrile group of 6-mercaptopurine (30.1.2.9) with 5-chloro-l-methyl-4-nitroimidazol in the presence of sodium acetate as a weak base [13]. 

Woodson LC, Ames MM, Selassie CD, Hansch C, Weinshilboum RM. Thio-purine methyltransferase aromatic thiol substrates and inhibition by benzioc acid derivatives. Mol Pharmacol 1983 24 471-478. 

METHYLNITROIMIDAZOLYLMERCAPTOPURINE 6-(T-METHYL-4 -NITRO-5 -IMIDAZOLYL)-MERCAPTO-PURINE 6-(METHYL-p-NITRO-5-IMIDAZOLYL)-THIOPURINE 6-(l-METHYL-p-NITRO-5-IMIDAZOL-YL)-THIOPURINE 6-((l-METHYL-4-NITROIMIDAZOL-5-YL)THIO)PURINE 6-(l-METHYL-4-NITROIMIDAZ-OL-5-YLTHIO)PURINE 6-((l-METHYL-4-NITRO-lH-IMDAZOL-5-YL)THIO)-lH-PURINE NCI-C03474 NSC-39084 RORASUL... 

Thio-purines are prepared from halo-purines or oxy-purines or by ring synthesis. One method for displacement of bromine with sulfur utilises TMS(CH2)2SH as a nucleophile, TBAF removal of the sulfur substim-ent then reveals the thione. In contrast with oxy-purines, in alkaline solution they readily alkylate on sulfur, rather than nitrogen. ... 

The formation of 8-0x0- or 8-thio-purines requires one-carbon components at a higher oxidation level urea and thiourea are appropriate. The products of chloroformate-initiated tive-membered ring cleavage of purines (27.1.1.3) can be recyclised to produce 8-oxo-purines." ... 

The sulfide-contraction process is ideally suited to introduce carbon substituents at various positions of purines and pyrimidines in nucleosides. Typically, a thio-purine or -pyrimidine was S-alkylated with electrophiles such as phenacyl bromide, ethyl bromoacetate or diethyl bromomalonate and then... 

The second method started from derivatives of 6-mercaptopurines and a-halogeno-alkyl or -aryl or -heteroaryl ketones with conversion to the respective 6-[(acylalkyl)thio]- or 6-[(aroylmethyl)thio]- or 6-[(heteroaroylmethyl)thio]-purines 138 and tautomeric 7-hydroxy-7,8-dihydrothiazolo[2,3-r]-purines 139. The final step of this synthesis was cyclodehydratation. 

One group of compounds that have proved to be particularly effective in interfering with DNA synthesis of tumour cells are the mercapto-purines and pyrimidines and their alkyl derivatives 6-mercaptopurine (6-MP) blocks the de novo synthesis of purines 9-(jS-D-arabinofuranosyl)-—9H—purine—6-thiol (ara—6-MP) inhibits the incorporation of L-aspartic acid and orotic acid into DNA cystosine 9-OS-D-xylo-furanosyl)—9H—purine—6-thiol (xyl—6-MP) inhibits the utilization of exogenously administered guanine the periodic acid oxidation product of 9-(/S-D-ribosyl)—6-methyl—thio purine (MMPR—OP) blocks the incorporation of thymidine into DNA . The effective clinical use of thiols... 

Hanai H, lida T, Takeuchi K, Arai O, Watanabe F, Abe J, Maruyama Y, Oohata A, Ikeya K, Kageoka M, Miwa I, Yoshirou S, Hosoda Y, Kubota T. Thio-purine maintenance therapy for ulcerative colitis the clinical significance of monitoring 6-thioguanine nucleotide. Infiamm Bowel Dis 2010 16(8) 1376-81. 

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... 

Pyrimidine-5-carboxamide, 4-amino-purine synthesis from, 5, 582 Pyrimidine-5-carboxamide, 4-amino- N- pheny synthesis, 3, 122 Pyrimidinecarboxamides Curtius degradation, 3, 82 dehydration, 3, 82 Hofmann degradation, 3, 82 hydrolysis, 3, 81 reactions, 3, 81 synthesis, 3, 127 Pyrimidinecarboxamides, thio-synthesis, 3, 128... 

Treatment of the allylic sulfoxide 1227 a with diisopropylethylamine (DIPEA) or of 1227 b with N-trimethylsilyldiethylamine 146 and TMSOTf 20 leads in ca. 90% yield to the quaternary amino derivatives 1228 and 1229 and HMDSO 7 [36] (Scheme 8.15). Tetramethylene sulfoxide 1230 reacts with silylated thymine 1231 in the presence of three equivalents of TMSOTf 20 to give the 4 -thio-nucleoside analogue 1232 and HMDSO 7 [37]. Other silylated pyrimidine, pyridine, and purine bases react analogously with cyclic sulfoxides to give 4 -thio-nucleoside analogues [37, 37a, 38]. 

---