Branched hetero polyethylene glycol and intermediate

Patent metadata

Field	Value
Publication number	US-10040761-B2
Application number	US-201113167777-A
Country	US
Kind code	B2
Filing date	Jun 24, 2011
Priority date	Jun 25, 2010
Publication date	Aug 7, 2018
Grant date	Aug 7, 2018

Abstract

A branched hetero polyethylene glycol according to the present invention is represented by the formula [1]:

wherein X and Y represent each an atomic group containing at least a functional group which reacts with a functional group present in a bio-functional molecule to form a covalent bond and the functional group contained in the atomic group X and the functional group contained in the atomic group Y are different from each other; s is an integer of 2 to 8, which represents the number of polyethylene glycol chains; n is the number of average added moles for the polyethylene glycol chain and 20≤n≤2000; and E is a branching linker moiety having s-valent bonding valency for the polyethylene glycol chains and having monovalent bonding valency for the functional group Y.

First claim

The invention claimed is:

1. A branched hetero polyethylene glycol represented by the formula [1]:

wherein X represents an atomic group containing at least a functional group which reacts with a functional group present in a bio-functional molecule to form a covalent bond and Y represents an atomic group consisting essentially of a functional group which reacts with a functional group present in a bio-functional molecule to form a covalent bond and a bonding moiety to be bonded to a branching linker moiety E selected from the group consisting of an ester bond, a urethane bond, an amide bond, an ether bond, a carbonate bond, a saturated hydrocarbon group containing a secondary amino group, a single bond, and a saturated hydrocarbon group, and the functional group contained in the atomic group X and the functional group contained in the atomic group Y are different from each other;
wherein as a combination of the functional group X and the functional group Y:
Y is a group selected from a maleimide group, a vinylsulfone group, an iodoacetamide group, an active carbonate group, an amino group, and an aminoxy group when X is an acetal group,
Y is a group selected from a maleimide group, a vinylsulfone group, an acetylene group, and an azide group when X is an aldehyde group,
Y is a group selected from an acetal group, an active carbonate group, an acetylene group, and an azide group when X is a maleimide group, a vinylsulfone group, or an iodoacetamide group,
Y is a group selected from an acetal group, a maleimide group, a vinylsulfone group, an iodoacetamide group, an acetylene group, and an azide group when X is an active ester group or an active carbonate group,
Y is a group selected from an acetal group, an acetylene group, and an azide group when X is an amino group or an aminoxy group,
Y is a group selected from an acetal group, an aldehyde group, a maleimide group, a vinylsulfone group, an iodoacetamide group, an active ester group, an active carbonate group, an amino group, and an aminoxy group when X is an acetylene group or an azide group, wherein the active ester group is a group represented by the following formula [9] which is reactive with nucleophilic groups:

wherein R 2 is a phenyl group, a 3-pyridyl group, a succinimide group, a 2-benzothiazole group, or a 1-benzotriazole group and W and W′ are each independently a linker comprising a covalent bond selected from the group consisting of an ester bond, a urethane bond, an amide bond, an ether bond, a carbonate bond, a saturated hydrocarbon group containing a secondary amino group, a single bond, and a saturated hydrocarbon group;
s is an integer of 2 or 4, which represents a number of polyethylene glycol chains;
n is a number of average added moles for the polyethylene glycol chain and 20≤n≤2000; and
E is a branching linker moiety represented by the formula [A] or [B]:

wherein each D is —(CH 2 ) a —O—(CH 2 ) b —, —(CH 2 ) a —O—C(O)—NH—(CH 2 ) b —, —O—C(O)—NH—(CH 2 ) b , —(CH 2 ) a —NH—C(O)—O—(CH 2 ) b —, —(CH 2 ) a —C(O)—NH(CH 2 ) b , or —(CH 2 ) a —NH—C(O)—(CH 2 ) b , or a single bond,
a=1-12,
b=1-12,
v=0 or 2, and
w=0 or 1.

2. The branched hetero polyethylene glycol according to claim 1 , which is represented by the formula [3] or [4]:

wherein v=0 or 2 and w=0 or 1.

3. The branched hetero polyethylene glycol according to claim 1 , wherein as the combination of the functional group X and the functional group Y:
Y is a group selected from a maleimide group, an active carbonate group, an amino group, and an aminoxy group when X is an acetal group,
Y is a group selected from an acetal group, an active carbonate group, an acetylene group, and an azide group when X is a maleimide group,
Y is a group selected from an acetal group, a maleimide group, an acetylene group, and an azide group when X is an active ester group or an active carbonate group,
Y is a group selected from an acetal group, an acetylene group, and an azide group when X is an amino group or an aminoxy group,
Y is a group selected from an acetal group, a maleimide group, an active ester group, an active carbonate group, an amino group, and an aminoxy group when X is an acetylene group or an azide group.

Assignees

• Yamamoto Yuji
• Yoshioka Hiroki
• Manabe Fumiaki
• Nof Corp

Inventors

• Yamamoto Yuji
• Yoshioka Hiroki
• Manabe Fumiaki

Classifications

• C08G65/33337

  cyclic · CPC title

• C07D207/452 Primary

  with hydrocarbon radicals, substituted by hetero atoms, directly attached to the ring nitrogen atom · CPC title

• C08G65/3344

  containing oxygen in addition to sulfur · CPC title

• C07D209/48

  with oxygen atoms in positions 1 and 3, e.g. phthalimide · CPC title

• C08G65/3312

  acyclic · CPC title