Patent ID: 6033909
Filing Date: 2000-03-07
Classification: C07B,C07H

Abstract:
An oligonucleotide analog of the formula I ##STR35## wherein: R.sup.1 is hydrogen, C.sub.1 -C.sub.18 -alkyl, C.sub.2 -C.sub.18 -alkenyl, C.sub.2 -C.sub.18 -alkynyl, C.sub.2 -C.sub.18 -alkylcarbonyl, C.sub.3 -C.sub.19 -alkenylcarbonyl, C.sub.3 -C.sub.19 -alkynylcarbonyl, C.sub.6 -C.sub.20 -aryl, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.8 -alkyl), or a radical of the formula II ##STR36## R.sup.2 is hydrogen, hydroxyl, C.sub.1 -C.sub.18 -alkoxy, halogen, azido or NH.sub.2 ;B is a conventional base in nucleotide chemistry;a is oxy or methylene;n is a number from 1 to 100;W is oxo, thioxo or selenoxo;V is oxy, thio, or imino;Y is oxy, thio, imino or methylene;Y' is oxy, thio, imino or (CH.sub.2).sub.m or V(CH.sub.2).sub.m ;m is a number from 1 to 18;X is hydroxyl or mercapto;U is hydroxyl, mercapto, SeH, C.sub.1 -C.sub.18 -alkoxy, C.sub.1 -C.sub.18 -alkyl, C.sub.6 -C.sub.20 -aryl, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.8)-alkyl, NHR.sup.3, NR.sup.3 R.sup.4 or a radical of the formula III(OCH.sub.2 CH.sub.2).sub.p O(CH.sub.2).sub.q CH.sub.2 R.sup.11(III)R.sup.3 is C.sub.1 -C.sub.18 -alkyl, C.sub.6 -C.sub.20 -aryl, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.8)-alkyl or 2-(CH.sub.2).sub.c -[NH(CH.sub.2).sub.c].sub.d -NR.sup.12 R.sup.12 ;c is a number from 2 to 6;d is a number from 0 to 6;R.sup.12 is independently hydrogen, C.sub.1 -C.sub.6 -alkyl or C.sub.1 .varies.C.sub.4 -alkoxy-C.sub.1 -C.sub.6 -alkyl;R.sup.4 is C.sub.1 -C.sub.18 -alkyl, C.sub.6 -C.sub.20 -aryl or (C.sub.6 -C.sub.10)-aryl-(C.sub.1 -C.sub.8)-alkyl, or in the case of NR.sup.3 R.sup.4 is, together with R.sup.3 and the nitrogen atom carrying them, a 5-6-membered heterocyclic ring, which can additionally contain a further hetero atom selected from the group comprising O, S and N;p is a number from 1 to 100;q is a number from 0 to 22;R.sup.11 is hydrogen or a functional group;Z=Z' are hydroxyl; mercapto; SeH; C.sub.1 -C.sub.22 -alkoxy; --O--(CH.sub.2).sub.b -NR.sup.12 R.sup.13, where b is a number from 1 to 6, and R.sup.13 is C.sub.1 -C.sub.6 -alkyl, or R.sup.12 and R.sup.13 together with the nitrogen atom carrying them form a 3-6-membered ring;C.sub.1 -C.sub.18 -alkyl; C.sub.6 -C.sub.20 -aryl; (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.8)-alkyl; (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.8)-alkoxy, where aryl is optionally substituted by 1, 2 or 3 identical or different radicals selected from the group comprising carboxyl, amino, nitro, C.sub.1 -C.sub.4 -alkylamino, C.sub.1 -C.sub.6 -alkoxy, hydroxyl, halogen and cyano;C.sub.1 -C.sub.18 -alkyl-mercapto; NHR.sup.3 ; NR.sup.3 R.sup.4 ; a radical of the formula III; or a group which favors intracellular uptake with the proviso that heteroaryl moieties containing 1 or 2 nitrogen atoms are excluded, or serves as the label for a DNA probe, or, during hybridization of the oligonucleotide analog to the target nucleic acid, attacks the latter with binding, crosslinking or cleavage, with the proviso that Z includes no functional moieties arising through cleavage of Z from a support; the curved bracket indicates that R.sup.2 and the neighboring phosphoryl residue can be located in the 2'- and 3'-position or else the opposite way round in the 3'- and 2'-position, where each nucleotide can be present in its D- or L-configuration and the base B can be located in the .alpha.- or .beta.-position, with the proviso that, if Z is hydroxyl, mercapto, methyl or ethoxy, at least one of the groups X, Y, Y', V and W is not hydroxyl, oxy or oxo, or R.sup.1 is not hydrogen or methylphosphonate monoester;or a physiologically tolerable salt thereof.