Back to results
US 2006/0142506 A1Published application
Heterobifunctional poly(ethylene glycol) and uses thereof
AssigneeIntezyne Technologies, Inc.
InventorsKurt Breitenkamp, Kevin Sill, Habib Skaff
Life of this patent
Estimating the term…
Abstract
The present invention provides bifunctional polymers, methods of preparing the same, and intermediates thereto. These compounds are useful in a variety of applications including the PEGylation of biologically active molecules. The invention also provides methods of using said compounds and compositions thereof.
Claims25
A method for preparing a compound of formula I:
- wherein:
- n is 10-2500;
- R1 is —X(CH2CH2Y)m(CH2)nR3, wherein:
- X is —O—, —S—, —C≡C—, or —CH2—;
- each Y is independently —O— or —S—;
- m is 0-10;
- n is 0-10;
- and
- R3 is —N3, —CN, a mono-protected amine, a di-protected amine, a protected aldehyde, a protected hydroxyl, a protected carboxylic acid, a protected thiol, a 9-30-membered crown ether, or an optionally substituted group selected from aliphatic, a 5-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a detectable moiety;
- R2 is halogen, N3, CN, a mono-protected amine, a di-protected amine, a protected hydroxyl, a protected aldehyde, a protected thiol, —NHR4, —N(R4)2, —SR4, —O(CH2CH2O)q(CH2)rR5, —OC(O)R4, or —OS(O)2R4;
- q and r are each independently 0-4;
- each R4 is independently an optionally substituted group selected from aliphatic, a 5-8-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10-membered saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a detectable moiety, or:
- two R4 on the same nitrogen atom are taken together with said nitrogen atom to form an optionally substituted 4-7-membered saturated, partially unsaturated, or aryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- and
- R5 is hydrogen, halogen, N3, CN, a mono-protected amine, a di-protected amine, a protected aldehyde, a protected hydroxyl, a protected carboxylic acid, a protected thiol, or an optionally substituted group selected from aliphatic, a 5-8-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10-membered saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a detectable moiety,
- from a compound of formula II:
- wherein:
- M is the cation of a suitable metal;
- n is 10-2500;
- R1 is —X(CH2CH2Y)m(CH2)nR3, wherein:
- X is —O—, —S—, —C≡C—, or —CH2—;
- each Y is independently —O— or —S—;
- m is 0-10;
- n is 0-10;
- and
- R3 is —N3, —CN, a mono-protected amine, a di-protected amine, a protected aldehyde, a protected hydroxyl, a protected carboxylic acid, a protected thiol, a 9-30-membered crown ether, or an optionally substituted group selected from aliphatic, a 5-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a detectable moiety;
- comprising the step of terminating the living polymer chain-end of the compound of formula II with a suitable polymerization terminator to afford a compound of formula I.
24 more elements
A compound of formula IV:
- wherein:
- n is 10-2500;
- R1 is —X(CH2CH2Y)m(CH2)nR3, wherein:
- X is —O—, —S—, —C≡C—, or —CH2—;
- each Y is independently —O— or —S—;
- m is 0-10;
- n is 0-10;
- R3 is —N3, —CN, a mono-protected amine, a di-protected amine, a protected aldehyde, a protected hydroxyl, a protected carboxylic acid, a protected thiol, a 9-30-membered crown ether, or an optionally substituted group selected from aliphatic, a 5-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a detectable moiety;
- and
- L1 is a suitable leaving group;
- provided that:
- (a) L1 is not —OMs when R3 is (EtO)2CH—, Bn-, or MeOC(O)—;
- (b) when R3 is CN— or CH3C(O)—, then L1 is not —OTs;
- and
- (c) L1 is not bromo when R2 is unsubstituted phenyl and R1 is
12 more elements
A compound of formula I′:
- wherein:
- n is 10-2500;
- R1 is —X(CH2CH2Y)m(CH2)nR3, wherein:
- X is —O—, —S—, —C≡C—, or —CH2—;
- each Y is independently —O— or —S—;
- m is 0-10;
- n is 0-10;
- and
- R3 is —N3, —CN, a mono-protected amine, a di-protected amine, a protected aldehyde, a protected hydroxyl, a protected carboxylic acid, a protected thiol, a 9-30 membered crown ether, or an optionally substituted group selected from aliphatic, a 5-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a detectable moiety;
- R2 is halogen, N3, CN, a mono-protected amine, a di-protected amine, a protected hydroxyl, a protected aldehyde, a protected thiol, —NHR4, —N(R4)2, —SR4, —O(CH2CH2O)q(CH2)rR5, —OC(O)R4, or —OS(O)2R4;
- q and r are each independently 0-4;
- each R4 is independently an optionally substituted group selected from aliphatic, a 5-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10-membered saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a detectable moiety, or:
- two R4 on the same nitrogen atom are taken together with said nitrogen atom to form an optionally substituted 4-7 membered saturated, partially unsaturated, or aryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- and
- R5 is hydrogen, halogen, N3, CN, a mono-protected amine, a di-protected amine, a protected aldehyde, a protected hydroxyl, a protected carboxylic acid, a protected thiol, or an optionally substituted group selected from aliphatic, a 5-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a detectable moiety,
- provided that:
- (a) when either of R1 or R2 is (EtO)2CH—, then the other of R1 or R2 is not —S—S-pyridin-2-yl, —OBn, —OC(O)C(CH3)═CH2, or —OC(O)CH═CH—CH═CH-Ph;
- (b) when either of R1 or R2 is —OBn, the other is not —OC(O)Cl;
- (c) R1 and R2 are not simultaneously —OC(O)CH═CH2;
- (d) when either of R1 or R2 is —CN, then the other is not -phthalimido;
- and
- (e) when either of R1 or R2 is acetyl, then the other is not —CN or -phthalimido.
19 more elements
Dependencies are inferred from the claim text.