PROTOTYPE SYSTEMS OF THERANOSTIC BIOMARKERS FOR IN VIVO MOLECULAR MANAGEMENT OF CANCER

• US 20180170953A1
• Filed: 01/10/2018
• Published: 06/21/2018
• 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
• Granted Patent: US 10,640,524 B2
• Time in Patent Office: Days
• 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 and at least one compound selected from the group consisting of a quinazoline-based tyrosine kinase inhibitor and a natural product;

wherein the beacon is an imaging agent that can be detected by one or more of optical, magnetic, radiofrequency (RF) or positron emission tomography (PET) detection methods.

2. A theranostic system according to claim 1, wherein the quinazoline-based tyrosine kinase inhibitor has the general structure defined by Formula I

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

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

5. A theranostic system according to claim 3 or claim 4, wherein R^1f represents

6. A theranostic system according to any one of claims 3 to 5 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-butl)phenyl or 1-napthylmethyl moiety.

7. A theranostic system according to any one of claims 2 to 6, 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.

8. A theranostic system according to any one of claims 2 to 7, wherein R³ represents a hydrogen atom, a halogen atom OR⁹, 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.

9. A theranostic system according to any preceding claim, wherein the natural product is a marine-derived natural product containing one or more aromatic rings and one or more hydroxyl groups, or a phytochemical natural product selected from the group consisting of (i) chromanols of the vitamin E superfamily, and precursors, analogues and derivatives thereof;

(ii) poly(oxo)phenolic compounds, and derivatives thereof;

(iii) retinoids, and analogues and derivatives thereof;

(iv) resveratrol, and precursors, analogues and derivatives thereof;

(v) flavonoids; and

(vi) terpenes and terpenoids.

10. A theranostic system according to any preceding claim, wherein the beacon is a coumarin, rhodamine, xanthene or cyanine dye or derivative thereof, a functionalised macrocyclic lanthanide complex, a poly-pyridyl near infra-red emitter transition metal complex, or a heterometallic compound or mixture with multimodal imaging properties comprising:

(1) a functionalised macrocyclic trivalent lanthanide complex; and

(2) a poly-pyridyl near infra-red emitter transition metal complex.

11. A theranostic system according to any preceding claim, wherein the beacon is a heterometallic compound of the general structure defined by Formula A

12. A theranostic system according to any one of claims 1 to 11, wherein the system comprises a complex of Formula B

13. A theranostic system according to any one of claims 1 to 11, wherein the system comprises a complex of Formula III or Formula IV

14. A theranostic system according to any one of claims 1 to 11, wherein the system comprises a complex of the natural product and the beacon represented by Formula H

15. A theranostic system according to any preceding claim for use in the treatment and diagnosis of cancer.