Valency platform molecules comprising carbamate linkages

• US 20030018190A1
• Filed: 08/13/2002
• Published: 01/23/2003
• Est. Priority Date: 12/09/1998
• Status: Abandoned Application

• Current Assignee: David S. Jones
• Original Assignee: David S. Jones
• Inventors: Jones, David S.
• Application Number:
  US10/219,237
• Publication Number:
  US 20030018190A1
• Time in Patent Office: Days
• US Class Current: 544/215
• CPC Class Codes: C07C 233/69 of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 271/16 to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 271/20 to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 233/56 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 249/08 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
• CPC Class Codes: C07D 295/205 Radicals derived from carbonic acid

Abstract

This invention pertains generally to valency molecules, such as valency platform molecules which act as scaffolds to which one or more molecules may be covalently tethered to form a conjugate. More particularly, the present invention pertains to valency platform molecules which comprise a carbamate linkage (i.e., —O—C(═O)—N<). In one aspect, the present invention pertains to valency platforms comprising carbamate linkages, which molecules have the structure of any one of Formulae I, II, or III, shown in FIG. 1. In one aspect, the present invention pertains to valency platforms comprising carbamate linkages, which molecules have the structure of any one of Formulae IV, V, or VI, shown in FIG. 8. The present invention also pertains to methods of preparing such valency platform molecules, conjugates comprising such valency platform molecules, and methods of preparing such conjugates.

Claims

1. A compound having the structure of one of the following formulae:

2. A compound according to claim 1, wherein said compound has the structure of Formula I.

3. A compound according to claim 1, wherein said compound has the structure of Formula II.

4. A compound according to claim 1, wherein said compound has the structure of Formula III.

5. A compound according to claim 1, wherein n is a positive integer from 2 to 4.

6. A compound according to claim 1, wherein y¹, y², and y³ are each 2.

7. A compound according to claim 1, wherein J is an oxygen atom.

8. A compound according to claim 1, wherein J is a covalent bond.

9. A compound according to claim 1, wherein R^C is selected from the group consisting of hydrocarbyl groups having from 1 to 20 carbon atoms.

10. A compound according to claim 1, wherein R^C is selected from the group consisting of:

—

CH₂—

;

—

CH₂CH₂—

;

—

CH₂CH₂CH₂—

;

11. A compound according to claim 1, wherein R^C is selected from the group consisting of organic groups consisting only of carbon, oxygen, and hydrogen atoms, and having from 1 to 20 carbon atoms.

12. A compound according to claim 1, wherein R^C is:

13. A compound according to claim 1, wherein each G¹, G², and G³ is independently selected from the group consisting of hydrocarbyl groups having from 1 to 20 carbon atoms.

14. A compound according to claim 1, wherein each G¹, G², and G³ is —

(CH₂)_q—

wherein q is a positive integer from 1 to 20.

15. A compound according to any one of claims 1, wherein each G¹, G², and G³ is independently selected from the group consisting of organic groups consisting only of carbon, oxygen, and hydrogen atoms, and having from 1 to 20 carbon atoms.

16. A compound according to claim 1, wherein each G¹, G², and G³ is:

17. A compound according to claim 1, wherein each R^N is independently selected from the group consisting of —

H, —

CH₃, and —

CH₂CH₃.

18. A compound according to claim 1, wherein each Z is —

NR^AR^B and is independently selected from the group consisting of;

20. A compound according to claim 19, wherein said compound has the structure of Formula IV.

21. A compound according to claim 19, wherein said compound has the structure of Formula V.

22. A compound according to claim 19, wherein said compound has the structure of Formula VI.

23. A compound according to claim 19, wherein n is a positive integer from 2 to 4.

24. A compound according to claim 19, wherein y¹, Y², and y³ are each 2.

25. A compound according to claim 19, wherein J is an oxygen atom.

26. A compound according to claim 19, wherein J is a covalent bond.

27. A compound according to claim 19, wherein R^C is selected from the group consisting of hydrocarbyl groups having from 1 to 20 carbon atoms.

28. A compound according to any claim 19, wherein R^C is selected from the group consisting of:

—

CH₂—

;

—

CH₂CH₂—

;

—

CH₂CH₂CH₂—

;

29. A compound according to claim 19, wherein R^C is selected from the group consisting of organic groups consisting only of carbon, oxygen, and hydrogen atoms, and having from 1 to 20 carbon atoms.

30. A compound according to claim 19, wherein R^C is:

31. A compound according to claim 19, wherein each G¹, G², and G³ is independently selected from the group consisting of hydrocarbyl groups having from 1 to 20 carbon atoms.

32. A compound according to claim 19, wherein each G¹, G², and G³ is selected from the group consisting of:

33. A compound according to claim 19, wherein each G¹, G², and G³ is independently selected from the group consisting of organic groups consisting only of carbon, oxygen, and hydrogen atoms, and having from 1 to 20 carbon atoms.

34. A compound according to claim 19, wherein each R^N is independently selected from the group consisting of —

H, —

CH₃, and —

CH₂CH₃.

35. A compound according to claim 19, wherein each Z is —

NR^AR^B and is independently selected from the group consisting of;

36. A conjugate comprising a compound according to claim 1 covalently linked to one or more biologically active molecules.

37. A conjugate according to claim 36, wherein said biologically active molecules are selected from the group consisting of:

oligonucleotides, peptides, polypeptides, proteins, antibodies, saccharides, polysaccharides, epitopes, mimotopes, and drugs.

39. The composition of claim 38, wherein said valency platform molecules have a polydispersity less than about 1.07.

40. The composition of claim 38, wherein each said valency platform molecules comprises at least 4 carbamate linkages and at least 8 reactive functional groups.

41. The composition of claim 38, wherein each said valency platform molecule comprises at least 4 identical reactive conjugating functional groups.

42. The composition of claim 38, wherein each said valency platform molecule comprises 2 to 32 carbamate linkages and 4 to 64 reactive functional groups.

43. The composition of claim 38, wherein comprising said valency platform molecules linked via said reactive functional groups to one or more biologically active molecules.

19. A compound having the structure of one of the following formulae:

38. A composition comprising valency platform molecules, wherein each said valency platform molecule comprises at least 2 carbamate linkages and at least 4 reactive conjugating functional groups;

and

wherein said valency platform molecules have a polydispersity less than about 1.2.

44. A composition comprising valency molecules, wherein each said valency molecule comprises at least two branches and at least four terminal groups;

wherein each said valency molecule comprises at least 2 carbamate linkages; and

wherein said valency molecules have a polydispersity less than about 1.2.

45. The composition of claim 44, wherein said valency molecules have a polydispersity less than about 1.07.

46. The composition of claim 44, wherein said valency molecules comprise at least 4 carbamate linkages, at least 4 branches and at least 8 terminal groups.