Benzamide compounds for cancer imaging and therapy

• US 6,447,748 B1
• Filed: 08/30/1999
• Issued: 09/10/2002
• Est. Priority Date: 05/06/1993
• Status: Expired due to Fees

• Current Assignee: Research Corporation Technologies
• Original Assignee: Research Corporation Technologies
• Inventors: Bowen, Wayne, McAfee, John G., Moody, Terry, John, Christy S., Baumgold, Jesse
• Primary Examiner(s): Hartley, Michael G.
• Application Number:
  US09/385,711
• Time in Patent Office: 1,107 Days
• Field of Search: 424/1.85, 424/1.81, 424/1.65, 424/1.41, 534/10, 564/305, 564/442
• US Class Current: 424/1.85
• CPC Class Codes: A61K 51/0406 Amines, polyamines, e.g. spermine, spermidine, amino acids, (bis)guanidines
• CPC Class Codes: A61K 51/0419 having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
• CPC Class Codes: A61K 51/0446 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 51/0455 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07B 2200/05 Isotopically modified compounds, e.g. labelled
• CPC Class Codes: C07B 59/00 Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
• CPC Class Codes: C07D 295/13 to an acyclic saturated chain
• CPC Class Codes: C07D 307/79 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring

Abstract

The present invention relates to a class of compounds having affinity for certain cancer cells, e.g. lung carcinomas, colon carcinomas, renal carcinomas, prostate carcinomas, breast carcinomas, malignant melanomas, gliomas, neuroblastomas and pheochromocytomas. The compounds of the present invention can also bind with high specificity to cell surface sigma receptors and can therefore be used for diagnostic imaging of any tissue having an abundance of cells with sigma receptors. The present invention provides such compounds as agents for diagnostic imaging and for detecting and treating tumors containing the cancer cells described above.

Claims

1. A method for diagnosing a mammal for the presence of a mammalian tumor which comprises administering to said mammal an effective diagnostic imaging amount of a compound having the formula:

wherein

Q is a radionuclide;

each R₁ and R_b are independently hydrogen, halide, lower alkyl or lower alkoxy;

R_a is lower alkoxy,

each R₃ is independently hydrogen or lower alkyl;

R₅ is N(R₃)₂;

q is an integer from 0 to 2; and

j and m are independently an integer from 0 to 6;

and performing radioimaging to diagnose the presence of said tumor.

3. The method of claim 1 wherein Q is a Υ

-emitting radionuclide.

4. The method of claim 3 wherein Q is ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I, ¹⁸F, ⁷⁶Br or ⁷⁷Br.

6. The method according to claim 1 or 2 wherein each R₁ is independently H, halo or lower alkoxy.

7. The method according to claim 1 or 2 wherein each R₁ is H.

8. The method according to claim 1 or 2 wherein q is 0 or 1.

9. The method according to claim 1 or 2 wherein m is 3 to 6.

10. The method according to claim 1 or 2 wherein j is 0.

11. The method of claim 1 or 2 wherein said tumor is a lung carcinoma, a colon carcinoma, a renal carcinoma, a melanoma, a glioma, a pheochromocytoma, prostate or breast carcinoma or a neuroblastoma.

12. The method of claim 11 wherein said lung carcinoma is an adenocarcinoma, a squamous carcinoma or a large cell lung carcinoma.

13. The method of claim 1 or 2 wherein said tumor comprises cancer cells which have a cell surface sigma receptor.

14. The method of claim 1 or 2 wherein said tumor comprises MCF-7 breast cancer cells.

15. The method of claim 1 or 2 wherein the tumor exists in women with dense breasts.

16. The method of claim 1 wherein the detection of the binding of said compound to a tumor is observed after about 6 to about 30 hours.

17. The method of claim 1 or 2 wherein said tumor comprises T47-D breast cancer cells.

18. The method of claim 1 or 2 comprises MDA-MB-231 breast cancer cells.

2. A method for treating a mammalian tumor which comprises administering to a mammal in need thereof a tumor-inhibiting effective amount of a compound having the formula:

wherein

Q is a radionuclide;

each R₁ and R_b are independently hydrogen, halide, lower alkyl or lower alkoxy;

R_a is lower alkoxy;

each R₃ is independently hydrogen or lower alkyl;

R₅ is N(R₃)₂;

q is an integer from 0 to 2; and

j and m are independently an integer from 0 to 6.

5. The method of claim 2 wherein Q is a β

-emitting or α

-emitting radionuclide.

19. A method for diagnostic imaging of a mammalian tissue which has cell surface sigma receptors which comprises administering to a mammal a diagnostic imaging effective amount of a compound of the formula:

wherein

Q is a radionuclide;

each R₁ and R_b are independently hydrogen, halide, lower alkyl or lower alkoxy;

R_a is lower alkoxy;

each R₃ is independently hydrogen or lower alkyl;

R₅ is N(R₃)₂;

q is an integer from 0 to 2; and

j and m are independently an integer from 0 to 6;

and performing radioimaging to diagnose said tissue which has cell surface sigma receptors.

20. The method of claim 19 wherein said tissue is brain tissue.

21. The method of claim 19 wherein said tissue is neural tissue.

22. The method of claim 19 wherein X is a Υ

-emitting radionuclide.

23. The method of claim 19 wherein X is ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I, ¹⁸F, ⁷⁶Br or ⁷⁷Br.

24. The method of claim 23 wherein X is ¹²³I.