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Chemical Compound Review:

AC1L8ZA3 6-chloro-5H-purin-2-amine

Synonyms: TL8000142

Majumdar, P. et al., Wang, J.Q. et al., Borthwick, A.D. et al., Kusmierek, J.T. et al., Rayat, S. et al., et al.

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Disease relevance of NSC29570

The 2-amino-6-chloropurine, 2-amino-6-(methylamino)purine, and the 2,6-diamino-8- azapurine derivatives also demonstrated significant activity against HSV-1 [1].
Also the 2-amino-6-chloropurine derivative was strongly active (EC50 = 0.1-0. 4 microg/mL) against herpes simplex viruses and (EC50 = 0.006-0.3 microg/mL) against CMV and VZV [2].

High impact information on NSC29570

[6-(18)O]-1r was prepared from 2-amino-6-chloropurine riboside using adenosine deaminase [3].
NaH-mediated alkylation of 6-chloropurine (4) and 2-amino-6-chloropurine (5) with certain alkyl bromides gave N7- and N9-alkylated derivatives (7a-d and 6a-d), the N9-isomer being the major product [4].
Cytosine, adenine, 2-amino-6-chloropurine, thymine, and (Z)-1,4-chloro-2-butene gave compounds 4c-f, which, after hydrolysis, afforded alcohols 4a, 4b, 4g, and 4h [5].
3'-CDG is not active against a strain of HSV-1 that lacks the thymidine kinase inducing capacity, whereas the carbocyclic analogue of 2-amino-6-chloropurine 3'-deoxyribofuranoside is active against that strain [6].
Comparative studies were performed with the related analog, 2-amino-6-chloropurine, which has been reported to produce a similar dual blockade of the purine pathway [7].

Biological context of NSC29570

Alkylation of 2-amino-6-chloropurine with 5-(2-bromoethyl)-2,2-dimethyl-1,3-dioxane (5) provided 2-amino-6-chloro-9-[2,(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]purine (6) in high yield [8].
For comparison, the furanosyl compound 9-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)guanine (17, AFG) was prepared by coupling 2-amino-6-chloropurine with 2-deoxy-2-fluoro-3,5-di-O-benzoyl-alpha- D-arabinofuranosyl bromide followed by base hydrolysis [9].

Associations of NSC29570 with other chemical compounds

As part of studies of the mechanism of oxanosine formation, the synthesis was attempted of [7- 18O]oxanosine by enzymatic 16O/18O-exchange with adenosine deaminase (ADA) in analogy to the synthesis of [6- 18O]guanosine from 2-amino-6-chloropurine [10].
The appropriate radiolabeling precursor N(2,9)-bis(p-anisyldiphenylmethyl)-O6-[4-(hydroxymethyl)benzyl]guanine (6) and reference standard O6-[4-(2-fluoroethoxymethyl)benzyl]guanine (O6-FEMBG, 1) were synthesized from 1,4-benzenedimethanol and 2-amino-6-chloropurine in four or six steps, respectively, with moderate to excellent chemical yields [11].
The Mitsunobu type of alkylation of 10 or 11 with adenine or 2-amino-6-chloropurine afforded phosphonates 12a, 12b, 13a, and 13b [12].
Alkylation of 6-chloropurine and 2-amino-6-chloropurine with bromoacetaldehyde diethyl acetal afforded 6-chloro-9-(2,2-diethoxyethyl)purine (3a) and its 2-amino congener (3b) [13].
D.c. polarography of 2-amino-6-chloropurine in aqueous medium over a broad pH range revealed two diffusion waves, the first of which corresponds to reduction of the C(6)-Cl bond, leading to formation of 2-aminopurine in high yield [14].

References

Synthesis and antiviral evaluation of carbocyclic analogues of ribofuranosides of 2-amino-6-substituted-purines and of 2-amino-6-substituted-8-azapurines. Shealy, Y.F., Clayton, J.D., Arnett, G., Shannon, W.M. J. Med. Chem. (1984) [Pubmed]
Structure-antiviral activity relationship in the series of pyrimidine and purine N-[2-(2-phosphonomethoxy)ethyl] nucleotide analogues. 1. Derivatives substituted at the carbon atoms of the base. Holý, A., Günter, J., Dvoráková, H., Masojídková, M., Andrei, G., Snoeck, R., Balzarini, J., De Clercq, E. J. Med. Chem. (1999) [Pubmed]
5-Cyanoimino-4-oxomethylene-4,5-dihydroimidazole and 5-cyanoamino-4-imidazolecarboxylic acid intermediates in nitrosative guanosine deamination: evidence from 18O-labeling experiments. Rayat, S., Majumdar, P., Tipton, P., Glaser, R. J. Am. Chem. Soc. (2004) [Pubmed]
Sulfinosine congeners: synthesis and antitumor activity in mice of certain N9-alkylpurines and purine ribonucleosides. Hanna, N.B., Bhattacharya, B.K., Robins, R.K., Avery, T.L., Revankar, G.R. J. Med. Chem. (1994) [Pubmed]
Unsaturated and carbocyclic nucleoside analogues: synthesis, antitumor, and antiviral activity. Phadtare, S., Kessel, D., Corbett, T.H., Renis, H.E., Court, B.A., Zimlicka, J. J. Med. Chem. (1991) [Pubmed]
Synthesis and antiviral evaluation of carbocyclic analogues of 2-amino-6-substituted-purine 3'-deoxyribofuranosides. Shealy, Y.F., O'Dell, C.A., Arnett, G. J. Med. Chem. (1987) [Pubmed]
Mode of action of 2-amino-6-chloro-1-deazapurine. Bennett, L.L., Smithers, D., Rose, L.M., Adamson, D.J., Brockman, R.W. Biochem. Pharmacol. (1984) [Pubmed]
Synthesis and antiviral activity of 9-[4-hydroxy-3-(hydroxymethyl)but-1-yl]purines. Harnden, M.R., Jarvest, R.L., Bacon, T.H., Boyd, M.R. J. Med. Chem. (1987) [Pubmed]
Fluorocarbocyclic nucleosides: synthesis and antiviral activity of 2'- and 6'-fluorocarbocyclic 2'-deoxy guanosines. Borthwick, A.D., Kirk, B.E., Biggadike, K., Exall, A.M., Butt, S., Roberts, S.M., Knight, D.J., Coates, J.A., Ryan, D.M. J. Med. Chem. (1991) [Pubmed]
Oxanosine is a substrate of adenosine deaminase. Implications for the quest for a toxicological marker for nitrosation activity. Majumdar, P., Wu, H., Tipton, P., Glaser, R. Chem. Res. Toxicol. (2005) [Pubmed]
Synthesis and preliminary biological evaluation of O6-[4-(2-[18F]fluoroethoxymethyl)benzyl]guanine as a novel potential PET probe for the DNA repair protein O6-alkylguanine-DNA alkyltransferase in cancer chemotherapy. Wang, J.Q., Kreklau, E.L., Bailey, B.J., Erickson, L.C., Zheng, Q.H. Bioorg. Med. Chem. (2005) [Pubmed]
Synthesis of "reversed" methylenecyclopropane analogues of antiviral phosphonates. Li, C., Zemlicka, J. Nucleosides Nucleotides Nucleic Acids (2007) [Pubmed]
Synthesis of base substituted 2-hydroxy-3-(purin-9-yl)-propanoic acids and 4-(purin-9-yl)-3-butenoic acids. Doláková, P., Masojídková, M., Holý, A. Nucleosides Nucleotides Nucleic Acids (2003) [Pubmed]
Preparative electrochemical reduction of 2-amino-6-chloropurine and synthesis of 6-deoxyacyclovir, a fluorescent substrate of xanthine oxidase and a prodrug of acyclovir. Kusmierek, J.T., Czochralska, B., Johansson, N.G., Shugar, D. Acta Chem. Scand., B, Org. Chem. Biochem. (1987) [Pubmed]

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