Back to results
US 5,637,684 AGranted
Phosphoramidate and phosphorothioamidate oligomeric compounds
AssigneeIsis Pharmaceuticals, Inc.
InventorsPhillip D. Cook, Oscar Acevedo, Normand Hebert
Life of this patent
Estimating the term…
Abstract
Compounds are provided having the structure: ##STR1## wherein the L groups are spanner or linker units, the Y and T group are functional groups for interacting with target molecules of interest, the X groups are oxygen or sulfur and the E groups are H, conjugate groups or intermediate groups used during the synthesis of the compounds are prepared using H phosphonate type chemistry wherein the functional groups are added during an oxidization step.
Claims21
A compound of the structure:
- ##STR3## wherein:
- X.sub.0 and each X.sub.m, independently, are O or S;
- Y.sub.0 and each Y.sub.m, independently, are H, or [Q.sub.2 ].sub.j --Z.sub.2 ;
- T.sub.0 and each T.sub.m, independently, are [Q.sub.1 ].sub.k --Z.sub.1, or together Y and T are joined in a nitrogen heterocycle;
- Q.sub.1, Q.sub.2, L.sub.0, L.sub.m+1 and each L.sub.m, independently, are C.sub.2 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.2 -C.sub.10 alkynyl, C.sub.4 -C.sub.7 carbocylo alkyl or alkenyl, a heterocycle, a polyalkyl glycol, or C.sub.7 -C.sub.14 aralkyl;
- E1 and E2, independently, are H, a hydroxyl protecting group, an activated solid support, a conjugate group, a reporter group, a polyethylene glycol, alkyl, oligonucleotide, peptide nucleic acid, a phosphate, a phosphite, an activated phosphate, or an activated phosphite;
- j and k independently are 0 or 1;
- m is 1 to about 50;
- Z.sub.1 and Z.sub.2, independently, are H, C.sub.1 -C.sub.2 alkyl, C.sub.2 -C.sub.20 alkenyl, C.sub.2 -C.sub.20 alkynyl, C.sub.6 -C.sub.14 aryl, C.sub.7 -C.sub.15 aralkyl, CH.dbd.O, OR.sub.1, SR.sub.2, NR.sub.3 R.sub.4, C(.dbd.NH)NR.sub.3 R.sub.4, CH(NR.sub.3 R.sub.4), NHC(.dbd.NH)NR.sub.3 R.sub.4, CH(NH.sub.2)C(.dbd.O)OH, C(.dbd.O)NR.sub.3 R.sub.4, C(.dbd.O)OR.sub.5, a metal coordination group, a reporter group, a nitrogen-containing heterocycle, a purine, a pyrimidine, a phosphate group, a polyether group, or a polyethylene glycol group;
- R.sub.1 is H, alkyl having 1 to about 6 carbon atoms, or a hydroxyl protecting group;
- R.sub.2 is H, alkyl having 1 to about 6 carbon atoms, or a thiol protecting group;
- R.sub.3 and R.sub.4 are, independently, H, alkyl having 1 to about 6 carbon atoms, or an amine protecting group;
- and
- R.sub.5 is H, alkyl having 1 to about 6 carbon atoms, or an acid protecting group.
11 more elements
A chimeric oligomeric compound having a first region comprising a phosphodiester or phosphorothioate oligonucleotide and a second region having the structure:
- ##STR6## wherein:
- X.sub.0 and each X.sub.m, independently, are O or S;
- Q.sub.1, Q.sub.2, L.sub.0, L.sub.m+1 and each L.sub.m, independently, are C.sub.2 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.2 -C.sub.10 alkynyl, C.sub.4 -C.sub.7 carbocylo alkyl or alkenyl, a heterocycle, an ether having 2 to 10 carbon atoms and 1 to 4 oxygen or sulfur atoms, a polyalkyl glycol, or C.sub.7 -C.sub.14 aralkyl;
- Y.sub.0 and each Y.sub.m, independently, are H, or [Q.sub.2 ].sub.j --Z.sub.2 ;
- T.sub.0 and each T.sub.m, independently, are [Q.sub.1 ].sub.k --Z.sub.1, or together Y and T are joined in a nitrogen heterocycle;
- j and k independently are 0 or 1;
- m is 1 to about 50;
- Z.sub.1 and Z.sub.2, independently, are H, C.sub.1 -C.sub.2 alkyl, C.sub.2 -C.sub.20 alkenyl, C.sub.2 -C.sub.20 alkynyl, C.sub.6 -C.sub.14 aryl, C.sub.7 -C.sub.15 aralkyl, a halogen, CH.dbd.O, OR.sub.1, SR.sub.2, NR.sub.3 R.sub.4, C(.dbd.NH)NR.sub.3 R.sub.4, CH(NR.sub.3 R.sub.4), NHC(.dbd.NH)NR.sub.3 R.sub.4, CH(NH.sub.2)C(.dbd.O)OH, C(.dbd.O)NR.sub.3 R.sub.4, C(.dbd.O)OR.sub.5, a metal coordination group, a reporter group, a nitrogen-containing heterocycle, a purine, a pyrimidine, a phosphate group, a polyether group, or a polyethylene glycol group;
- R.sub.1 is H, alkyl having 1 to about 6 carbon atoms, or a hydroxyl protecting group;
- R.sub.2 is H, alkyl having 1 to about 6 carbon atoms, or a thiol protecting group;
- R.sub.3 and R.sub.4 are, independently, H, alkyl having 1 to about 6 carbon atoms, or an amine protecting group;
- R.sub.5 is H, alkyl having 1 to about 6 carbon atoms, or an acid protecting group;
- and
- where one of E.sub.1 and E.sub.2 comprises said phosphodiester or phosphorothioate oligonucleotide and the other of said E.sub.1 and E.sub.2 is H, a hydroxyl protecting group or a conjugate group.
11 more elements
Dependencies are inferred from the claim text.