N-aryl-carbamic acid ester-derived and valeric acid ester-derived cross-linkers and conjugates, and methods for their synthesis and use

• US 6,887,952 B1
• Filed: 02/12/2004
• Issued: 05/03/2005
• Est. Priority Date: 02/12/2004
• Status: Active Grant

• Current Assignee: Biosite Diagnostics Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: BIOSITE INCORPORATED (Abbott Laboratories Incorporated)
• Inventors: Buechler, Kenneth F., Banaszczyk, Mariusz G., Noar, Joseph Barry
• Primary Examiner(s): Seidleck, James J.
• Assistant Examiner(s): ZEMEL, IRINA SOPJIA
• Application Number:
  US10/778,919
• Time in Patent Office: 446 Days
• Field of Search: 525/523, 525/54.1, 548/543, 548/545, 548/563
• US Class Current: 525/532
• CPC Class Codes: C07D 207/46 with hetero atoms directly attached to the ring nitrogen atom

Abstract

The present invention describes carbamic acid ester-derived and valeric acid ester-derived polyfunctional cross-linker molecules, and methods for their synthesis and use. The inclusion of polymeric moieties such as poly(alkylene oxide) in the cross-linkers of the present invention can provide advantageous solubility properties in aqueous environments. Such cross-linkers may be used to form conjugates for use in a variety of assay formats.

Claims

1. A compound of the formula:

wherein X is (alkylene oxide)_n;

n is between about 40 to about 450; and

Y and Z are independently arylene or heteroarylene units having 5 or 6 ring atoms, optionally substituted with from 1 to 4 substituents independently selected from the group consisting of C_1-6 alkyl straight or branched chain, halogen, trihalomethyl, C_1-6 alkoxy, —

NO₂, —

NH₂, —

OH, —

COOR′

, where R′

is H or lower alkyl, —

CH₂OH, —

CONH₂, and a linkage to a poly(alkylene oxide) moiety, wherein Z is optionally present.

2. A compound according to claim 1 having the formula:

wherein X is (alkylene oxide)_n;

n is between about 40 to about 450; and

each R is independently selected from the group consisting of C_1-6 alkyl straight or branched chain, halogen, trihalomethyl, C_1-6 alkoxy, NO₂, NH₂, OH, —

COOR′

, where R′

is H or lower alkyl, CH₂OH, CONH₂, and a linkage to a polyalkylene oxide moiety.

3. A compound according to claim 1, wherein said (alkylene oxide), group is a copolymer of two or more units selected from the group consisting of methylene oxide, ethylene oxide, propylene oxide, isopropylene oxide, and butylene oxide.

4. A compound according to claim 1, wherein said (alkylene oxide), group is a homopolymer of units selected from the group consisting of methylene oxide, ethylene oxide, propylene oxide, isopropylene oxide, and butylene oxide.

5. A compound according to claim 1 having the formula:

wherein n is between about 40 to about 450.

6. A composition comprising a plurality of compounds of claim 1, wherein said plurality of compounds comprise an average number of (alkylene oxide)_n groups of between 60 and 100.

7. A composition according to claim 6, wherein said plurality of compounds comprise an average number of (alkylene oxide)_n groups of between 70 and 90.

8. A composition according to claim 6, wherein said plurality of compounds comprise an average number of (alkylene oxide)_n groups of about 77.

9. A composition according to claim 6 comprising a plurality of compounds of claim 5, wherein said plurality of compounds comprise an average number of (alkylene oxide), groups of about 77.