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US 2004/0171860 A1Published application
Novel acylating reagents
OwnerHong Zhao, Richard B. Greenwaldinventors
Life of this patent
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Abstract
Novel acylating agents useful for preparing activated nucleophiles such as terminally activated polymers are disclosed. In preferred aspects, the acylating agents are 1 and they used to prepare activated polymers such as PEG's for conjugating small molecules, proteins, polypeptides and the like.
Claims24
A compound having the formula:
- 33
- wherein:
- Y1-3 are independently O, S or NR1;
- Z1 and Z2 are independently selected substituted or unsubstituted aromatic hydrocarbons or substituted or unsubstituted heterocyclic aromatic groups containing an aldehyde or protecting group, and
- R1 is selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxys, phenoxys and C1-6 heteroalkoxys.
2 more elements
A method of preparing an activated nucleophile, comprising:
- a) reacting a compound having the formula:
- 42
- wherein:
- Y1-3 are independently O, S or NR1;
- Z1 and Z2 are independently selected substituted or unsubstituted aromatic hydrocarbons or substituted or unsubstituted heterocyclic aromatic groups containing an aldehyde or protecting group;
- and
- R1 is selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxys, phenoxys and C1-6 heteroalkoxys;
- with a strong nucleophile under conditions sufficient to form a compound of formula (II):
- 43
- wherein:
- R8 is a residue of a strong nucleophile;
- Y4 is NR20, O or S;
- Y1-2 are independently O, S or NR1;
- Z2 is a substituted or unsubstituted aromatic hydrocarbon or substituted or unsubstituted heterocyclic aromatic group containing an aldehyde or protecting group;
- and
- R1 and R20 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-8 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxys, phenoxys and C1-6 heteroalkoxys.
13 more elements
A method of preparing an activated nucleophile, comprising:
- a) reacting a compound having the formula:
- 49
- wherein:
- Y1-3 are independently O, S or NR1;
- Z5 and Z6 are independently selected substituted or unsubstituted aromatic hydrocarbons or substituted or unsubstituted heterocyclic aromatic groups, substituted with
- 50
- wherein
- R1 and R6-7 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxys, phenoxys and C1-6 heteroalkoxys;
- p is a positive integer;
- and
- with a nucleophile under conditions sufficient to form a compound of Formula (IIa):
- 51
- wherein:
- R8′ is a nucleophile residue;
- L1 is a bifunctional linker
- Y1-2 are independently O, S or NR1;
- Z6 is a substituted or unsubstituted aromatic hydrocarbon or substituted or unsubstituted heterocyclic aromatic group, substituted with
- 52
- and
- R1, R6-7, and R20 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxys, phenoxys and C1-6 heteroalkoxys.
17 more elements
Dependencies are inferred from the claim text.