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US 5,783,682 AGranted
Oligonucleotide mimics having nitrogen-containing linkages
AssigneeIsis Pharmaceuticals, Inc.
InventorsPhillip D. Cook, Yogesh S. Sanghvi
Life of this patent
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Abstract
Novel compounds that mimic and/or modulate the activity of wild-type nucleic acids. In general, the compounds contain a selected sequence of nucleosidic bases or other reactive groups that are covalently bound through nitrogen-containing linear, hairpin, dumbbell, and circular shaped tethers.
Claims7
A compound having structure:
- ##STR5## wherein:
- each R.sub.N is, independently, H, -T-L, alkyl having 1 to about 10 carbon atoms;
- alkenyl having 2 to about 10 carbon atoms;
- alkynyl having 2 to about 10 carbon atoms;
- aryl having 7 to about 14 carbon atoms;
- or heterocyclic;
- provided that at least one R.sub.N is not H or alkyl;
- each Q is, independently, N--R.sub.N, O, or CH.sub.2, provided that at least one Q is not CH.sub.2 ;
- k is zero or 1;
- each A is, independently, an aromatic ring;
- N--R.sub.N ;
- C(O);
- a single bond;
- or (CH.sub.2).sub.m where m is 1-5;
- each T is, independently, a single bond, a methylene group or a group having structure II:
- --CR.sup.1 --R.sup.2 !.sub.n --B--CR.sup.1 R.sup.2 !.sub.o --D!.sub.p--N(R.sub.N)!.sub.q -- II
- where:
- D is C(O), C(S), C(R.sup.1) (NR.sup.3 R.sup.4), CH.sub.2 R.sup.1, CHR.sup.1 R.sup.2, or NR.sup.3 R.sup.4 ;
- B is a single bond, CH.dbd.CH, C.tbd.C, O, S or NR.sup.4 ;
- each R.sup.1 and R.sup.2 is independently selected from the group consisting of hydrogen, alkyl or alkenyl having 1 to about 12 carbon atoms, hydroxy- or alkoxy- or alkylthio-substituted alkyl or alkenyl having 1 to about 12 carbon atoms, hydroxy, alkoxy, alkylthio, amino and halogen;
- R.sup.3 and R.sup.4, independently, are H, -T-L, alkyl having 1 to about 10 carbon atoms;
- alkenyl having 2 to about 10 carbon atoms;
- alkynyl having 2 to about 10 carbon atoms;
- aryl having 7 to about 14 carbon atoms;
- heterocyclic;
- or
- R.sup.3 and R.sup.4, together, are cycloalkyl having 3 to about 10 carbon atoms or cycloalkenyl having 4 to about 10 carbon atoms;
- n and o, independently, are zero to 5;
- q is zero or 1;
- p is zero to about 10;
- and
- each L is, independently, a nucleosidic base, an amino acid side chain, an aromatic hydrocarbon, a heterocycle moiety containing nitrogen, sulfur, and/or oxygen;
- a carbohydrate, a drug, a reporter molecule;
- an RNA cleaving group;
- a group for improving the pharmacokinetic properties of the compound;
- or a group for improving the pharmacodynamic properties of the compound;
- or group capable of hydrogen bonding.
34 more elements
A compound having the structure:
- ##STR6## each R.sub.N is, independently, H, -T-L, alkyl having 1 to about 10 carbon atoms;
- alkenyl having 2 to about 10 carbon atoms;
- alkynyl having 2 to about 10 carbon atoms;
- aryl having 7 to about 14 carbon atoms;
- or heterocyclic;
- provided that at least one R.sub.N is not H or alkyl;
- each Q is, independently, N--R.sub.N, O, or CH.sub.2, provided that at least one Q is not CH.sub.2 ;
- k is zero or 1;
- zz is from 1 to about 90;
- each A is, independently, an aromatic ring;
- N--R.sub.N ;
- C(O);
- a single bond;
- or (CH.sub.2).sub.m where m is 1-5;
- each T is, independently, a single bond, a methylene group or a group having structure II:
- --CR.sup.1 R.sup.2 !.sub.n--B--CR.sup.1 R.sup.2 !.sub.o --D!.sub.p --N(R.sub.N)!.sub.q -- II
- where:
- D is C(O), C(S), C(R.sup.1) (NR.sup.3 R.sup.4), CH.sub.2 R.sup.1, CHR.sup.1 R.sup.2, or NR.sup.3 R.sup.4 ;
- B is a single bond, CH.dbd.CH, C.tbd.C, O, S or NR.sup.4 ;
- each R.sup.1 and R.sup.2 is independently selected from the group consisting of hydrogen, alkyl or alkenyl having 1 to about 12 carbon atoms, hydroxy- or alkoxy- or alkylthio-substituted alkyl or alkenyl having 1 to about 12 carbon atoms, hydroxy, alkoxy, alkylthio, amino and halogen;
- R.sup.3 and R.sup.4, independently, are H, -T-L, alkyl having 1 to about 10 carbon atoms;
- alkenyl having 2 to about 10 carbon atoms;
- alkynyl having 2 to about 10 carbon atoms;
- aryl having 7 to about 14 carbon atoms;
- heterocyclic;
- or
- R.sup.3 and R.sup.4, together, are cycloalkyl having 3 to about 10 carbon atoms or cycloalkenyl having 4 to about 10 carbon atoms;
- n and o, independently, are zero to 5;
- q is zero or 1;
- p is zero to about 10;
- and
- each L is, independently, a nucleosidic base, an amino acid side chain, an aromatic hydrocarbon, a heterocycle moiety containing nitrogen, sulfur, and/or oxygen;
- a carbohydrate, a drug, a reporter molecule;
- an RNA cleaving group;
- a group for improving the pharmacokinetic properties of the compound;
- or a group for improving the pharmacodynamic properties of the compound;
- or group capable of hydrogen bonding.
34 more elements
Dependencies are inferred from the claim text.