Radiolabeled farnesyl-protein transferase inhibitors

• US 6,060,038 A
• Filed: 05/07/1998
• Issued: 05/09/2000
• Est. Priority Date: 05/15/1997
• Status: Expired due to Fees

• Current Assignee: Merck & Co., Inc.
• Original Assignee: Merck & Co., Inc.
• Inventors: Eng, Wai-Si, Burns, Hugh D., Gibson, Raymond E.
• Primary Examiner(s): Dees, Jose' G.
• Assistant Examiner(s): Hartley, Michael G.
• Application Number:
  US09/074,346
• Time in Patent Office: 733 Days
• Field of Search: 424/1.81, 424/1.85, 424/1.89, 424/1.65, 544/224, 544/358, 544/366, 544/386, 544/392, 544/406, 544/336, 548/311.1, 548/335.3, 548/343.5, 548/517, 435/15, 436/504, 514/18, 514/317, 514/400, 514/450, 514/252, 514/255, 549/266, 549/271, 549/293, 549/320
• US Class Current: 424/1.81
• CPC Class Codes: A61K 2123/00 Preparations for testing in vivo
• CPC Class Codes: A61K 51/0459 having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
• CPC Class Codes: C07D 403/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C12Q 1/48 involving transferase

Abstract

The present invention is directed toward radiolabeled farnesyl-protein transferase inhibitor compounds which are useful to label FPTase in assays, whether cell-based, tissue-based or in whole animal. The tracers can also be used in competitive binding assays to obtain information on the interaction of unlabeled FTIs with FPTase.

Claims

1. A radiolabeled compound which is selected from:

##STR80## or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of claim 1.

4. A method of diagnostic imaging of farnesyl-protein transferase binding sites in tissues of a mammalian species which comprises administering to the mammalian species in need of such diagnostic imaging an effective amount of the compound according to claim 1 and performing a radioactive scan to obtain an image.

6. A method of evaluation of cancer in tissues of a mammalian species which comprises administering to the mammalian species in need of such evaluation an effective amount of the compound according to claim 1 and performing a radioactive scan to obtain an image.

8. The method according to claim 6 wherein the cancer arises by mutation in the ras gene or mutation in a protein that can regulate Ras activity.

2. A radiolabeled compound of the formula ##STR81## or pharmaceutically acceptable salt thereof, which has been radiolabeled with a radionuclide selected from ³ H, ¹¹ C, ¹⁸ F, ¹²⁵ I and ¹²³ I, provided that if ³ H or ¹¹ C is selected, the radionuclide is incorporated at the terminal methyl moiety of the side chain attached to the C5 position of the piperazinone ring.

5. A method of diagnostic imaging of farnesyl-protein transferase binding sites in tissues of a mammalian species which comprises administering to the mammalian species in need of such diagnostic imaging an effective amount of the compound according to claim 2 and performing a radioactive scan to obtain an image.

7. A method of evaluation of cancer in tissues of a mammalian species which comprises administering to the mammalian species in need of such evaluation an effective amount of the compound according to claim 2 and performing a radioactive scan to obtain an image.