| 摘要 |
<p>Hydrazide-substituted nucleoside or nucleotide analogs (I) are new. Nucleoside or nucleotide analogs of formula (I) are new. [Image] R 1H; mono-, di- or tri-phosphate group; or protective group such as DMT; R 2, R' 2H, OH, phosphoramidite (or derivative), H-phosphonate or chain terminator T; R 3, R' 3H, OH, halo, 1-6C alkyl or OR 5; R 51-6C alkyl; R 45-membered heterocycle of formula (a) (e.g. pyrrole, pyrazole, imidazole, 1,2,4-triazole or tetrazole), 6-membered heterocycle (preferably of formula (b)) or purine analog of formula (c), (a)-(c) being bonded to the sugar residue at N and to E at C; E : optionally substituted, saturated or unsaturated spacer arm comprising 0-20C and optionally heteroatoms; X : CH, CR 6, or N; R 6halo, 1-6C alkyl, OR 7or SR 7; R 71-6C alkyl; Y 1NH 2, N=C(Z 1)(Z 2) or NH-CHZ 1Z 2; Y 2, Y 3H, OH, O, NH 2, halo, amine, amido or 1-6C alkyl; Z 1, Z 2H or organic group. [Editor's note: DMT is not defined in the specification.] Independent claims are included for: (i) the preparation of (I); (ii) libraries of compounds (I); (iii) nucleic acids (II) containing at least one compound (I). (iv) a method for identifying compounds capable of introducing a mutation into a nucleic acid, by incorporating (I; Y = NH 2) in a synthetic oligonucleotide, reacting with an aldehyde or ketone (or a library of aldehydes and/or ketones) optionally followed by reduction, replicating the oligonucleotide using a polymerase (specifically an exo-DNA polymerase) and determining whether a mutation has been introduced into the newly synthesized strand; (v) a method for point mutation of a nucleic acid, by preparing a synthetic oligonucleotide containing at least one compound (I) and replicating as in (iv); (vi) a method for random mutation of a nucleic acid involving using a reaction mixture containing at least one compound (I) for the amplification of a nucleic acid; (vii) a method for identifying a compound capable of inhibiting a polymerase (specifically a reverse transcriptase or kinase), by testing the activity of the enzyme in presence of at least one compound (I); (viii) a method for identifying a compound capable of inhibiting viral reverse transcriptase, by testing the effect of at least one compound (I) (in the form of a nucleoside analog) on infected cells; and (ix) a kit for the amplification and/or detection of a target nucleic acid, containing (I) or (II). ACTIVITY : Virucide; cytostatic. MECHANISM OF ACTION : Polymerase inhibitor; reverse transcriptase inhibitor; nucleotide kinase inhibitor; antisense nucleic acid.</p> |
