Molecule labelling using 2-hydraninopyridine derivatives

• US 5,679,778 A
• Filed: 06/30/1995
• Issued: 10/21/1997
• Est. Priority Date: 11/05/1992
• Status: Expired due to Term

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Johnson Matthey PLC
• Inventors: Bridger, Gary J., Ultee, Michael E., Abrams, Michael J., Schwartz, David A., Padmanabhan, Sreenivasan
• Primary Examiner(s): NORTHINGTON DAVIS, ZINNA
• Application Number:
  US08/432,204
• Time in Patent Office: 844 Days
• Field of Search: 546/366, 546/264, 514/353, 530/391.5, 534/14
• US Class Current: 530/391.5
• CPC Class Codes: C07D 213/80 in position 3
• CPC Class Codes: C07D 213/82 in position 3
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links

Abstract

A compound of formula I ##STR1## in which E is an alkenyl group or represents H₂ in which case the compound is in acid addition salt form, J is selected from --CO--NH--, --CO--O--, --CO--S-- and --NH--CO--, T is an alkylene chain, or, if J is --CO--NH--, T is the residue of an amino acid moiety, Q is a hydrophilic or cleavable moiety, and Z is an amine- and/or thiol-reactive moiety. Conjugates formed by reacting such compound with a macromolecule, e.g. an immunoglobulin, and labelled macromolecules comprising a metal atom bound to such conjugate are also disclosed.

Claims

1. A compound of formula I, ##STR4## in which E is an alkylidene group or represent H₂ in which case the compound is in an acid addition salt form,

J is selected from --CO--NH--, CO--O--, --CO--S-- and --NH--CO--,

T is an alkylene chain, or, if J is --CO--NH--, T is the residue of an amino acid moiety,

Q is a hydrophilic moiety or a moiety cleavable by metabolism in normal body organs and blood, and

Z is an amine- and/or thiol-reactive moiety, or

Q and Z together form a group which has both hydrophilic or cleavable and amine- and/or thiol-reactive functions.

2. A compound according to claim 1 wherein E represents a straight or branched chain lower alkylidene group.

3. A compound according to claim 1 or 2 wherein -Q-Z is α

-bromoacetyl, α

-bromoacetamidyl or a mixed substituted or unsubstituted pyridyl disulphide.

5. The compound of claim 1 which is:

##STR6## or its acid addition salt wherein Su represents succinimidyl.

6. The compound of claim 1 which is:

##STR7## or its acid addition salt wherein Su represents succinimidyl.

7. The compound of claim 1 which is:

##STR8## or its acid addition salt wherein Su represents succinimidyl.

8. The compound of claim 1 which is:

##STR9## or its acid addition salt.

9. The compound of claim 1 which is:

##STR10## or its acid addition salt.

10. The compound of claim 1 which is:

##STR11## or its acid addition salt and wherein R is H or CH₃.

11. The compound of claim 1 which is:

##STR12## or its acid addition salt.

12. The compound of claim 1 which is:

##STR13## or its acid addition salt.

13. The compound of claim 1 which is:

##STR14## or its acid addition salt.

14. The compound of claim 1 which is:

##STR15## or its acid addition salt.

15. The compound of claim 1 which is:

##STR16## or its acid addition salt.

16. The compound of claim 1 which is:

##STR17## or its acid addition salt.

17. The compound of claim 1 which is:

##STR18## or its acid addition salt wherein Su represents succinimidyl.

18. The compound of claim 1 which is:

##STR19## or its acid addition salt wherein Su represents succinimidyl.

19. The compound of claim 1 which is:

##STR20## or its acid addition salt.

20. The compound of claim 1 which is:

##STR21## or its acid addition salt.

21. The compound of claim 1 which is:

##STR22## or its acid addition salt.

22. A conjugate comprising the reaction product of a macromolecule with a compound according to claim 1.

23. A conjugate according to claim 22, wherein the macromolecule comprises an immunoglobulin or a fragment thereof.

24. A labelled macromolecule comprising a metal atom bound to a conjugate according to claim 22.

25. A labelled macromolecule according to claim 24, wherein the metal is selected from radioisotopes of Tc and Re.

4. A compound of formula Ia, ##STR5## wherein E is alkenyl or H₂,

R is H or CH₃, and

R'"'"' is H or NO₂.

26. A compound of formula II ##STR23## in which E is alkenyl or H₂.

27. A compound of formula ##STR24## in which E is an alkylidene group or represents H₂ in which case the compound is in acid addition salt form,

X is selected from O and NH,

one or both of Y and Z comprise an amine or thiol reactive moiety and a hydrophilic moiety or a moiety cleavable by metabolism in normal organs or blood,

n indicates an alkylene chain, and

R¹ -R³ are selected from H and methyl.