Halogenated compounds for cancer imaging and treatment and methods for their use

Patent metadata

Field	Value
Publication number	US-9375496-B2
Application number	US-201414481727-A
Country	US
Kind code	B2
Filing date	Sep 9, 2014
Priority date	Sep 9, 2013
Publication date	Jun 28, 2016
Grant date	Jun 28, 2016

Abstract

Compounds having a structure of Formula I:

or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , X 1 , X 2 , X 3 and X 4 are as defined herein, and wherein the compound comprises at least one F, Cl, Br, I or 123 I moiety, are provided. Uses of such compounds for imaging diagnostics in cancer and therapeutics methods for treatment of subjects in need thereof, including prostate cancer as well as methods and intermediates for preparing such compounds are also provided.

First claim

The invention claimed is:

1. A compound having a structure of Formula I:

or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein:
R 1 and R 2 are each independently H or C 1 -C 10 alkyl, or R 1 and R 2 , together with the carbon atom to which they are bound, are taken together to form a carbocyclic or heterocyclic ring;
R 3 is H or C 1 -C 10 alkylcarboyl;
R 4 and R 5 are each independently H, C 1 -C 10 alkyl or C 1 -C 10 alkylcarbonyl; and
X 1 , X 2 , X 3 and X 4 are each independently H, F, Cl, Br, I or 123 I,
wherein at least one of X 1 , X 2 , X 3 or X 4 is 123 I.

2. The compound of claim 1 , wherein the compound has one of the following structures (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig) or (Ih):

3. The compound of claim 1 , wherein three of X 1 , X 2 , X 3 and X 4 are H, and the remaining X 1 , X 2 , X 3 or X 4 is 123 I.

4. The compound of claim 1 , wherein X 1 is F, Cl, Br or I or 123 I.

5. The compound of claim 1 , wherein X 3 is F, Cl, Br or I or 123 I.

6. The compound of claim 1 , wherein R 1 and R 2 are each C 1 -C 10 alkyl.

7. The compound of claim 6 , wherein C 1 -C 10 alkyl is methyl.

8. The compound of claim 1 , wherein at least one of R 3 , R 4 or R 5 is H.

9. The compound of claim 1 , wherein R 3 , R 4 and R 5 are each H.

10. The compound of claim 1 , wherein at least one of R 4 or R 5 is C 1 -C 10 alkyl.

11. The compound of claim 1 , wherein R 4 and R 5 are each C 1 -C 10 alkyl.

12. The compound of claim 11 , wherein C 1 -C 10 alkyl is methyl, isopropyl or n-butyl.

13. The compound of claim 1 , wherein at least one of R 3 , R 4 or R 5 is C 1 -C 10 alkylcarbonyl.

14. The compound of claim 1 , wherein R 3 , R 4 and R 5 are each C 1 -C 10 alkylcarbonyl.

15. The compound of claim 14 , wherein C 1 -C 10 alkylcarbonyl is methyl carbonyl.

16. The compound of claim 1 , wherein the compound has one of the following Structures:

or a pharmaceutically acceptable salt or stereoisomer thereof.

17. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.

18. A method of imaging cancer, the method comprising administering a compound of claim 1 to a subject and detecting the presence or absence of cancer by use of SPECT or PET.

19. The method of claim 18 , wherein the method identifies the presence or absence of a tumor.

20. The method of claim 18 , wherein the method identifies the location of a tumor.

21. The method of claim 18 , wherein the cancer is prostate cancer.

22. A pharmaceutical composition comprising a compound of claim 1 , an additional therapeutic agent and a pharmaceutically acceptable carrier, wherein the additional therapeutic agent is enzalutamide, galeterone, ODM-201, ARN-509, abiraterone, bicalutamide, nilutamide, flutamide, cyproterone acetate, docetaxel, Bevacizumab (Avastin), OSU-HDAC42, VITAXIN, sunitumib, ZD-4054, Cabazitaxel (XRP-6258), MDX-010 (Ipilimumab), OGX 427, OGX 011, finasteride, dutasteride, turosteride, bexlosteride, izonsteride, FCE 28260, SKF105,111 or related compounds thereof.

23. A method of imaging cancer, the method comprising administering the pharmaceutical composition of claim 17 to a subject and detecting the presence or absence of cancer by use of SPECT or PET.

Assignees

• Univ British Columbia
• British Columbia Cancer Agency

Inventors

• Andersen Raymond John
• Banuelos Carmen Adriana
• Garcia Fernandez Javier
• Imamura Yusuke
• Kunzhong Jian
• Mawji Nasrin R
• Sadar Marianne Dorothy
• Wang Jun
• Tien Amy Hsing Chen

Classifications

• A61P5/28

  Antiandrogens · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• C07C69/63

  of saturated acids · CPC title