Back to results
US 7,202,264 B2Granted
Supports for oligomer synthesis
AssigneeIsis Pharmaceuticals, Inc.
InventorsVasulinga Ravikumar, Muthiah Manoharan, Andrei P. Guzaev, Zhiwei Wang, Raju Krishna Kumar
Life of this patent
Estimating the term…
Abstract
Universal linkers, their facile processes of manufacture and methods of using the same are provided.
Claims34
A compound of formula (II):
- wherein:
- A is independently selected from hydrogen, a blocking group, SM, L-SM, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aliphatic ether, a substituted or unsubstituted aromatic, a substituted or unsubstituted heteroaromatic;
- or a substituted or unsubstituted heterocyclic;
- SM is a support medium;
- L is (C═O)—(CH2)n—(C═O)O—, where n is an integer from 1 to 20;
- G1 is independently selected from O, S, (CR1R2)h, NR3, O—(C═O), or (C═O)—O;
- each of R1 and R2 is independently selected from hydrogen, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aromatic, a substituted or unsubstituted heteroaromatic, or a substituted or unsubstituted heterocyclic;
- R3 is independently selected from hydrogen, a blocking group, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aromatic, a substituted or unsubstituted heteroaromatic, or a substituted or unsubstituted hetero cyclic;
- each of RU, RV, RW, RX, RY, and RZ is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- each of Q and W is independently selected from hydrogen, a blocking group, L, SM, L-SM, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aromatic, substituted or unsubstituted heteroaromatic, a substituted or unsubstituted heterocyclic, a protected or unprotected nucleosidyl moiety, a protected or unprotected nucleosidyl moiety attached through a phospholinker, or a protected or unprotected oligonucleotidyl moiety;
- each of Y1 and Y2 is independently selected from O, S, NR3, or CR1R2;
- and
- h is 1, 2, or 3
- wherein at least one of A, Q, and W is SM or L-SM.
11 more elements
A process of making a compound of formula (II):
- wherein:
- A is independently selected from hydrogen, a blocking group, SM, L-SM, a substituted or unsubstituted, saturated, partially saturated or unsaturated aliphatic group, a substituted or substituted, saturated, partially saturated or unsaturated aliphatic ether, a substituted or unsubstituted aromatic, substituted or unsubstituted heteroaromatic, or a substituted or unsubstituted heterocyclic;
- G1 is independently selected in O, S, CR1R2, or NR3;
- each of R1 and R2 is independently selected from hydrogen, a substituted or unsubstituted, saturated, partially saturated or unsaturated aliphatic group, substituted or unsubstituted aromatic, substituted or unsubstituted heteroaromatic, or substituted or unsubstituted heterocyclic;
- R3 is independently selected from hydrogen, a blocking group, a saturated, partially saturated or unsaturated aliphatic group, substituted or unsubstituted aromatic, substituted or unsubstituted heteroaromatic, or substituted or unsubstituted heterocyclic;
- each of RU, RV, RW, RX, RY, and RZ is independently selected from hydrogen, substituted or unsubstituted allyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- each of Q and W is independently selected from hydrogen, a blocking group, SM, L-SM, a substituted or unsubstituted, a saturated, or partially saturated aliphatic group, a substituted or unsubstituted aromatic, substituted or unsubstituted heteroaromatic, a substituted or unsubstituted heterocyclic, a protected or unprotected nucleosidyl moiety, a protected or unprotected nucleosidyl moiety attached through a phospholinker, or a protected or unprotected oligonucleotidyl moiety;
- SM is a support medium;
- L is a bifunctional linking moiety;
- and
- each of Y1 and Y2 is independently selected from O, S, NR3, or CR1R2;
- wherein at least one of A, Q, and W is SM or L-SM;
- the process comprising,
- providing a compound of formula (V):
- and
- reacting said compound of formula (VII) with a primary amine of formula (VIII):
- NH2-A, wherein A is as defined above.
14 more elements
A process for functionalizing a support medium with a first monomeric subunit, the process comprising:
- providing a support-bound compound of formula (II):
- wherein:
- A is independently selected from hydrogen;
- a blocking group;
- SM;
- L-SM;
- a substituted or unsubstituted aliphatic group;
- a substituted or unsubstituted aliphatic ether;
- unsaturated a substituted or unsubstituted aromatic;
- substituted or unsubstituted heteroaromatic;
- or a substituted or unsubstituted heterocyclic;
- SM is a support medium;
- L is (C═O)—(CH2)n—(C═O)O—, where n is an integer from 1 to 20;
- G1 is independently selected from O, S, CR1R2, or NR3;
- each of R1 and R2 is independently selected from hydrogen, a substituted or unsubstituted, saturated, partially saturated or unsaturated aliphatic group, substituted or unsubstituted aromatic, substituted or unsubstituted heteroaromatic, or substituted or unsubstituted heterocyclic;
- R3 is independently selected from hydrogen, a blocking group, substituted or unsubstituted aliphatic group, substituted or unsubstituted aromatic, substituted or unsubstituted heteroaromatic, or substituted or unsubstituted heterocyclic;
- each of RU, RV, RW, RX, RY, and RZ is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- one of Q or W is SM or L-SM, and the other of Q or W is a blocking group;
- and
- each of Y1 and Y2 is independently selected from O, S, NR3, or CR1R2;
- deblocking one of Q or W to give a reactive hydroxyl;
- and
- treating said reactive hydroxyl with a first monomeric subunit having a further protected hydroxyl group to form a monomer-functionalized support medium.
20 more elements
Dependencies are inferred from the claim text.