ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
To improve cell permeability, monomeric 3′-deoxyadenosine (cordycepin) and antivirally active trimeric 3′-deoxyadenylyl-(2′-5′)-3′-deoxyadenylyl-(2′-5′)-3′-deoxyadenosine (2′-5′)d3 (A-A-A); (cordycepin-trimer core) were modified at the 2′-O- or 5′-O-position by myristic, cholic, and folic acid = tetradecanoic, 3α, 7α, 12α -trihy-droxy-5β-cholan-24-oic, and N-{4-{[(2-amino-3,4-dihydro-4-oxopteridin-6-yl)methyl]amino}benzoyl}-L-glutamic acid, resp., linked by a 6-aminohexamoyl spacer. Syntheses of the trimeric educts 21, 27, and 28 were performed by phosphoramidite chemistry, using β-eliminating 2-(4-nitrophenyl)ethyl (npe), 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) and (9H-fluoren-9-yl)methoxycarbonyl (fmoc) groups which allow a deprotection by DBU in an aprotic solvent without harming the ester-bounded conjugates, to give the products 24-26 and 31-33. The metabollically stable (2′-5′)A derivatives 26 and 33, covalently linked to folic acid either at the 2′-terminus or at the 5′-terminus of (2′-5′)d3′(A-A-A), respectively, are a new class of the anti-HIV-1 compounds. Inhibition of HIV-1 reverse transcriptase (RT) activity by 26 and 33 was 45 and 81%, respectively. Only 33 activated recombinant, human RNase L by 35%.
Additional Material:
1 Tab.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19970800405
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