PHOTODYNAMIC THERAPEUTIC COMPOUNDS AND PHOTODYNAMIC METHODS OF TREATMENT

• US 20190307725A1
• Filed: 12/05/2017
• Published: 10/10/2019
• Est. Priority Date: 12/05/2016
• Status: Active Grant

• Current Assignee: Salt And Light Pharmaceuticals Pty., Ltd.
• Original Assignee: Salt And Light Pharmaceuticals Pty., Ltd.
• Inventors: ZENG, Jun, TANG, Xinyu, Palmer, James T
• Granted Patent: US 11,147,797 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/409 having four such rings, e.g. porphine derivatives, bilirubin, biliverdine hemin, hematin A61K31/555
• CPC Class Codes: A61K 41/0057 Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 487/22 in which the condensed system contains four or more hetero rings

Abstract

The invention provides photodynamic therapeutic compounds and photodynamic methods of treatment. The photodynamic therapeutic compounds may be activated by long wavelength light. The photo-activation by long wavelength light may allow improved tissue penetration. The compounds are selected from the group consisting of compounds of formula (i), or a pharmaceutically acceptable salt thereof: formula (i) wherein PDC is a photodynamic core and wherein R1; R2; R3; and R4 are H, phenyl, pyridine-4-yl, methylpyridinium, N-methylpyridinium-3-yl; 2-phenyl-N-methylpyridinium-4-yl, 3-phenyl-N-methylpyridinium-4-yl, 4-phenyl-N-methylpyridinium-4-yl, 2-phenyl-N-methylpyridinium-3-yl, 3-phenyl-N-methylpyridinium-3-yl or 4-phenyl-N-methylpyridinium-3-yl; and wherein any one or more of R1, R2, R3 and R4 may be optionally substituted.

Claims

1. An asymmetric compound selected from the group consisting of compounds of formula (i),

2. The compound of claim 1 wherein the PDC comprises any suitable molecular structure or chromophore activated or photochemically excited when exposed to light.

3. The compound of claim 1 wherein the PDC absorbs visible light between 420 nm and 520 nm.

4. The compound of claim 1 wherein the PDC comprise a cyclic tetrapyrrole.

5. The compound of claim 4 wherein the cyclic tetrapyrrole comprises a porphin, a porphyrin, a chlorin or a corrin.

6. The compound of claim 1 wherein the compound of formula (i) comprises an absorption band at 620 to 700 nm.

11. The compound of claim 1 wherein any two neighbouring R groups are identical.

15. The compound of claim 1 wherein the compound of formula (i) comprises far-infrared absorption spectroscopic properties to absorb far-infrared light penetrating through skin to tumour cells.

16. The compound of claim 1 wherein the compound of formula (i) blocks Ras-Raf interaction.

17. The compound of claim 1 wherein the compound of formula (i) disrupts Ras-dependent signalling.

18. The compound of claim 1 wherein the compound of formula (i) specifically targets oncogenic Ras protein in human tumour cells.

19. A pharmaceutical composition comprising an effective amount of the compound of claim 1, and a pharmaceutically acceptable carrier, diluent and/or excipient.

20. The pharmaceutical composition of claim 19 when used for the treatment or prophylaxis of a cancer, or associated disease, disorder or condition.

21. A method of treating a cancer, or associated disease, disorder or condition in a patient including the step of administering an effective amount of the compound of claim 1 to the patient, to thereby treat the cancer, or associated disease, disorder or condition.

22. The method of claim 21 further comprising photo-activating the administered compound to release radical oxygen species with cytotoxicity.

23. The method of claim 22 wherein the photoactivation comprises long wavelength light.

24. The method of claim 23 wherein the long wavelength light comprises a wavelength of between 600 nm and 850 nm.

25. The method of claim 22 wherein the photoactivation comprises long wavelength light of a wavelength of about 660 nm and/or about 637 nm.

26. A compound of claim 1 when used in the treatment of a cancer, or associated disease, disorder or condition.

27. Use of a compound of claim 1 in the manufacture of a medicament for the treatment of a cancer, or associated disease, disorder or condition.

28. The compound of claim 1 wherein the cancer, or associated disease, disorder or condition is one or more of a skin cancer, a lung cancer, a pancreatic cancer, a colon cancer, an ovarian cancer, an adenocarcinoma, a leukemia (AML), and a lymphoma.

30. The compound of claim 1 wherein R1 is substituted with halo selected from the group consisting of Cl, F, Br, and I.

31. The compound of claim 1 wherein the cancer, or associated disease, disorder or condition is associated with activation of Ras-mediated signalling.

7. A compound selected from the group consisting of compounds of formula (I), or a pharmaceutically acceptable salt thereof wherein R1, R2, R3 and R4 comprise;

8-10. -10. (canceled)

12-14. -14. (canceled)

29. (canceled)