Radiolabelled benzamide analogues, their synthesis and use in diagnostic imaging

• US 7,659,400 B2
• Filed: 06/01/2007
• Issued: 02/09/2010
• Est. Priority Date: 07/31/2003
• Status: Active Grant

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Tu, Zhude, Mach, Robert H.
• Primary Examiner(s): Seaman; D. Margaret
• Assistant Examiner(s): Chandrakumar; Nizal S
• Application Number:
  US11/757,246
• Publication Number:
  US 20080107599A1
• Time in Patent Office: 984 Days
• Field of Search: 546/86, 546/87, 424/1.85, 424/1.81
• US Class Current: 546/86
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 51/04 Organic compounds
• CPC Class Codes: A61K 51/0497 conjugates with a carrier being an organic compounds
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07C 323/41 Y being a hydrogen or an acyclic carbon atom
• CPC Class Codes: C07D 217/04 with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• CPC Class Codes: C07D 257/02 not condensed with other rings
• CPC Class Codes: C07D 295/13 to an acyclic saturated chain

Abstract

Fluoroalkoxybenzamide compounds which selectively bind Sigma-2 receptors are disclosed. These compounds, when labelled with ¹⁸F, can be used as radiotracers for imaging of tumors by positron emission tomography (PET). In addition, these compounds, when labelled with ¹²³I, can be used as radiotracers for imaging of tumors by single photon emission computed tomography (SPECT). Methods for synthesis of these compounds are also disclosed.

Claims

1. A radiolabelled fluoroalkoxybenzamide compound of structure

2. A radiolabelled fluoroalkoxybenzamide compound or a salt thereof in accordance with claim 1, wherein the compound has a structure selected from the group consisting of

3. A radiolabelled fluoroalkoxybenzamide compound or a salt thereof in accordance with claim 1, wherein m=2, n=4, R₁ is H, and R₂ is CH₃.

4. A radiolabelled fluoralkoxybenzamide compound or a salt thereof in accordance with claim 1, wherein m=2, n=4, R₁ is H, and R₂ is Br.

5. A radiolabelled fluoroalkoxybenzamide compound or a salt thereof in accordance with claim 1, wherein m=2, n=4, R₁ is H, and R₂ is I.

6. A radiolabelled fluoroalkoxybenzamide compound or a salt thereof in accordance with claim 1, wherein m=2, n=4, R₁ is OCH₃, and R₂ is I.

7. A compound of structure

8. A compound or salt thereof in accordance with of claim 7, wherein m=2 and n=4.

9. A compound or salt thereof in accordance with claim 7, wherein R is selected from the group consisting of H and C_1-4 alkoxy.

10. A compound or salt thereof in accordance with claim 7, wherein the C_1-4 alkoxy is a methoxy.