Degradable polyethylene glycol derivative having disulfide linker

Patent metadata

Field	Value
Publication number	US-11220576-B2
Application number	US-201816493909-A
Country	US
Kind code	B2
Filing date	Mar 23, 2018
Priority date	Mar 30, 2017
Publication date	Jan 11, 2022
Grant date	Jan 11, 2022

Abstract

A degradable polyethylene glycol derivative represented by formula (1). R1, R2, and R4 represent each independently a hydrogen atom or a hydrocarbon group having from 1 to 6 carbon atoms, and at least one of R1, R2, R3 and R4 is the hydrocarbon group; P1 is a straight-chain or branched polyethylene glycol chain having a number of ethylene glycol units of 3 or more; P2 is a straight-chain polyethylene glycol chain having a number of ethylene glycol units of 3 or more; w is an integer of 1 to 8; u is an integer of 1 to 10; X1 is a chemically reactive functional group; and Z1, Z2 and Z3 are each independently a selected divalent spacer.

First claim

The invention claimed is:

1. A degradable polyethylene glycol derivative represented by formula (1):

wherein, in the formula (1), R 1 , R 2 , R 3 , and R 4 represent each independently a hydrogen atom or a hydrocarbon group having from 1 to 6 carbon atoms, and at least one of R 1 , R 2 , R 3 , and R 4 is the hydrocarbon group; P 1 is a straight-chain or branched polyethylene glycol chain having a number of ethylene glycol units of 3 or more; P 2 is a straight-chain polyethylene glycol chain having a number of ethylene glycol units of 3 or more; 2 is an integer of 1 to 8; u is an integer of 1 to 10; X 1 is a chemically reactive functional group; and Z 1 , Z 2 , and Z 3 are each independently a selected divalent spacer.

2. The degradable polyethylene glycol derivative as claimed in claim 1 , wherein a sum of number of carbon atoms in R 1 , R 2 , R 3 and R 4 is from 1 to 6.

3. The degradable polyethylene glycol derivative as claimed in claim 1 , wherein w is 1.

4. The degradable polyethylene glycol derivative as claimed in claim 3 , wherein P 1 is a straight-chain polyethylene glycol chain having a hydrocarbon group or a chemically reactive functional group at a terminal thereof.

5. The degradable polyethylene glycol derivative as claimed in claim 4 , wherein P 1 is represented by the following formula (2):
X 2 —Z 4 —(OCH 2 CH 2 ) n —  (2)

wherein, in the formula (2), X 2 is a chemically reactive functional group different from X 1 or a methoxy group; Z 4 is a divalent spacer; and n is an integer of 3 to 2,000.

6. The degradable polyethylene glycol derivative as claimed in claim 1 , wherein w is from 2 to 8.

7. The degradable polyethylene glycol derivative as claimed in claim 4 , wherein P 1 is represented by formula (3):

wherein in the formula (3), X 2 is a chemically reactive functional group different from X 1 or a methoxy group; Z 4 is a divalent spacer; n is an integer of 3 to 1,000; and a is 0 or 2.

8. The degradable polyethylene glycol derivative as claimed in claim 6 , wherein P 1 is represented by formula (4):

wherein in the formula (4), X 2 is a chemically reactive functional group different from X 1 or a methoxy group; Z 4 is a divalent spacer; n is an integer of 3 to 1,000; and a is 0 or 2.

9. The degradable polyethylene glycol derivative as claimed in claim 6 , wherein P 1 is selected from the group consisting of formula (r), formula (s), formula (t), formula (u) and formula (v):

wherein, in the formula (r), the formula (s), the formula (t), the formula (u) and the formula (v), n is an integer of 3 to 2,000; and w is 2 in a case where P 1 is represented by the formula (r), w is 3 in a case where P 1 is represented by the formula (s), w is 4 in a case where P 1 is represented by the formula (t), w is 4 in a case where P 1 is represented by the formula (u), and w is 8 in a case where P 1 is represented by the formula (v).

10. The degradable polyethylene glycol derivative as claimed in claim 1 , wherein P 2 is represented by formula (5):
—(OCH 2 CH 2 ) m —  (5)

wherein, in the formula (5), m is an integer of 3 to 2,000.

11. The degradable polyethylene glycol derivative as claimed in claim 1 , wherein X 1 is selected from the group consisting of an active ester group, an active carbonate group, an aldehyde group, an isocyanate group, an isothiocyanate group, an epoxy group, a maleimide group, a vinyl sulfone group, an acryl group, a sulfonyloxy group, a carboxy group, a thiol group, a dithiopyridyl group, an α-haloacetyl group, an alkynyl group, an allyl group, a vinyl group, an amino group, an oxyamino group, a hydrazide group and an azide group.

12. The degradable polyethylene glycol derivative as claimed in claim 1 , wherein Z 1 , Z 2 and Z 3 are each independently an ether bond, an ester bond, a carbonate bond, a urethane bond, an amide bond, a secondary amino group, an alkylene group containing any of these bonds and group, a single bond or an alkylene group.

13. The degradable polyethylene glycol derivative as claimed in claim 5 , wherein X 2 is selected from the group consisting of an active ester group, an active carbonate group, an aldehyde group, an isocyanate group, an isothiocyanate group, an epoxy group, a maleimide group, a vinyl sulfone group, an acryl group, a sulfonyloxy group, a carboxy group, a thiol group, a dithiopyridyl group, an α-haloacetyl group, an alkynyl group, an allyl group, a vinyl group, an amino group, an oxyamino group, a hydrazide group, a methoxy group and an azide group.

14. The degradable polyethylene glycol derivative as claimed in claim 2 , wherein w is 1.

15. The degradable polyethylene glycol derivative as claimed in claim 14 , wherein P 1 is a straight-chain polyethylene glycol chain having a hydrocarbon group or a chemically reactive functional group at a terminal thereof.

16. The degradable polyethylene glycol derivative as claimed in claim 15 , wherein P 1 is represented by the following formula (2):
X 2 —Z 4 —(OCH 2 CH 2 ) n —  (2)

wherein, in the formula (2), X 2 is a chemically reactive functional group different from X 1 or a methoxy group; Z 4 is a divalent spacer; and n is an integer of 3 to 2,000.

17. The degradable polyethylene glycol derivative as claimed in claim 2 , wherein w is from 2 to 8.

18. The degradable polyethylene glycol derivative as claimed in claim 15 , wherein P 1 is represented by formula (3):

wherein in the formula (3), X 2 is a chemically reactive functional group different from X 1 or a methoxy group; Z 4 is a divalent spacer; n is an integer of 3 to 1,000; and a is 0 or 2.

19. The degradable polyethylene glycol derivative as claimed in claim 17 , wherein P 1 is represented by formula (4):

wherein in the formula (4), X 2 is a chemically reactive functional group different from X 1 or a methoxy group; Z 4 is a divalent spacer; n is an integer of 3 to 1,000; and a is 0 or 2.

20. The degradable polyethylene glycol derivative as claimed in claim 17 , wherein P 1 is selected from the group consisting of formula (r), formula (s), formula (t), formula (u) and formula (v):

wherein, in the formula (r), the formula (s), the formula (t), the formula (u) and the formula (v), n is an integer of 3 to 2,000; and w is 2 in a case where P 1 is represented by the formula (r), w is 3 in a case where P 1 is represented by the formula (s), w is 4 in a case where P 1 is represented by the formula (t), w is 4 in a case where P 1 is represented by the formula (u), and w is 8 in a case where P 1 is represented by the formula (v).

Assignees

• Nof Corp

Inventors

• Tange Kota
• Yoshioka Hiroki
• TSUBUSAKI Takuma
• Kamiya Masaki

Classifications

• C08G65/3342

  having sulfur bound to carbon and hydrogen · CPC title

• C08G65/334 Primary

  containing sulfur · CPC title

• C08G75/14

  Polysulfides · CPC title

• C08G65/2636

  the other compounds containing sulfur · CPC title

• C08G75/00 Primary

  Macromolecular compounds obtained by reactions forming a linkage containing sulfur with or without nitrogen, oxygen, or carbon in the main chain of the macromolecule · CPC title