Prototype systems of theranostic biomarkers for in vivo molecular management of cancer

• US 9,890,187 B2
• Filed: 06/26/2015
• Issued: 02/13/2018
• Est. Priority Date: 06/26/2015
• Status: Active Grant

• Current Assignee: EPOS-Iasis Research and Development, Ltd.
• Original Assignee: EPOS-Iasis Research and Development, Ltd.
• Inventors: Odysseos, Andreani, Pitris, Costas, Keramidas, Anastasios
• Primary Examiner(s): Jarrell, Noble E
• Application Number:
  US14/751,795
• Publication Number:
  US 20160376298A1
• Time in Patent Office: 963 Days
• Field of Search: None
• CPC Class Codes: A61K 49/0021 the fluorescent group being a small organic molecule
• CPC Class Codes: A61K 49/0052 Small organic molecules oligomers, polymers, dendrimers A61K49/0054
• CPC Class Codes: C07F 15/0053 without a metal-carbon linkage

Abstract

The present invention relates to a theranostic system comprising a beacon and a compound selected from the group consisting of a quinazoline-based tyrosine kinase inhibitor and a natural product. The theranostic systems have use in the therapy and diagnosis of tyrosine kinase related malignancies.

Claims

1. A theranostic system comprising a beacon in combination with or covalently linked to at least one compound selected from the group consisting of:

a quinazoline-based tyrosine kinase inhibitor and

a natural product;

wherein the beacon is a heterometallic compound having a structure as defined by Formula A

2. A theranostic system according to claim 1, wherein the quinazoline-based tyrosine kinase inhibitor is an anilinoquinazoline-based tyrosine kinase inhibitor having the structure defined by Formula II

3. A theranostic system according to claim 2, wherein R^1e represents a hydrogen atom and R^1f represents an optionally substituted aryl, aralkyl, heterocyclyl or heterocyclylalkyl group.

4. A theranostic system according to claim 2 wherein R^1f represents

5. A theranostic system according to claim 2 wherein R^1f represents a 2-methoxyphenyl, 2-bromophenyl, 2-fluorophenyl, 2-chlorophenyl, 3-methoxyphenyl, 3-bromophenyl, 3-fluorophenyl, 3-chlorophenyl, 3,5,difluorophenyl, 3,5,dichlorophenyl, 3,5,dibromophenyl, 3-(trifluoromethyl)phenyl, 4-chloro-3-(trifluoromethyl)phenyl, 3-chloro-4-fluorophenyl, 4-fluoro-3-(trifluoromethyl)phenyl, 4-fluorophenyl, 4-methoxyphenyl, 4-bromophenyl, 4-chlorophenyl, 4-isopropylphenyl, 3-bromo-5-(trifluoromethyl)phenyl, bis(trifluoromethyl)phenyl, 4-(tert-butyl)phenyl or 1-napthylmethyl moiety.

6. A theranostic system according to claim 1, wherein R² represents a hydrogen atom, a halogen atom OR^c, N(R^c)(R^d), SR^c or an optionally substituted alkyl group;

wherein Rc and Rd each independently represent a hydrogen atom or an optionally substituted alkyl or acyl group.

7. A theranostic system according to claim 1, wherein R³ represents a hydrogen atom, a halogen atom OR^g, N(R^g)(R^h), SR^g or an optionally substituted alkyl, alkenyl or alkynyl group;

wherein R^g and R^h each independently represent a hydrogen atom or an optionally substituted alkyl, acyl, alkenyl or alkynyl group.

8. A theranostic system according to claim 1, wherein the system comprises a complex of Formula B

9. A theranostic system according to claim 1, wherein the system comprises a complex of Formula III or Formula IV

10. A theranostic system according to claim 2, wherein R² represents a hydrogen atom, a halogen atom, OR^c, N(R^c)(R^d), SR^c or an optionally substituted alkyl group;

wherein R^c and R^d each independently represent a hydrogen atom or an optionally substituted alkyl or acyl group.

11. A theranostic system according to claim 2, wherein R³ represents a hydrogen atom, a halogen atom OR^g, N(R^g)(R^h), SR^g or an optionally substituted alkyl, alkenyl or alkynyl group;

wherein R^g and R^h each independently represent a hydrogen atom or an optionally substituted alkyl, acyl, alkenyl or alkynyl group.

12. A theranostic system according to claim 1, comprising said beacon in combination with or complexed to said quinazoline-based tyrosine kinase inhibitor.

13. A theranostic system according to claim 1, comprising said beacon in combination with or complexed to said natural product.

14. A theranostic system according to claim 1, comprising said beacon in combination with or complexed to said quinazoline-based tyrosine kinase inhibitor and further comprising said natural product.

15. A theranostic system according to claim 1, wherein R² is selected from the group consisting of —

NHC(═

O)CH₂Cl, —

SC(═

O)CH₂Cl, —

OC(═

O)CH₂Cl, —

NHC(═

O)CH₂Br, —

SC(═

O)CH₂Br, —

OC(═

O)CH₂Br, —

NHC(═

O)CH₂F, —

SC(═

O)CH₂F, and —

OC(═

O)CH₂F.

16. A theranostic system according to claim 1, wherein R³ is selected from the group consisting of a hydrogen atom or OR^m or NH(R^m), wherein R^m is an acroyl, crotonoyl, pentenoyl or pentadienoyl group, or wherein R^m is selected from the group consisting of: