RADIOLABELLED BENZAMIDE ANALOGUES, THEIR SYNTHESIS AND USE IN DIAGNOSTIC IMAGING

• US 20100150836A1
• Filed: 12/21/2009
• Published: 06/17/2010
• 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
• Granted Patent: US 7,947,838 B2
• Time in Patent Office: Days
• US Class Current: 424/1.890
• 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 method of imaging a tumor in a mammal, the method comprising:

administering to the mammal a radiolabelled fluoroalkoxybenzamide compound of structure

wherein m is an integer from 1 to about 10, n is an integer from 1 to about 10, and R₁ and R₂ are each independently selected from the group consisting of H, a halogen selected from the group consisting of I, Br, Cl and F, a C_1-4 alkoxy, a C_1-4 alkyl, a C_1-4 fluoroalkyl, a C_1-4 fluoroalkoxy, CF₃, OCF₃, SCH₃, SCF₃, and NH₂, or a salt thereof; and

subjecting the mammal to positron emission tomography (PET) scanning.

2. A method of imaging a tumor in accordance with claim 1, wherein m=2, n=4, R₁ is selected from the group consisting of H and OCH₃, and R₂ is selected from the group consisting of CH₃, Br and I.

3. A method of imaging a tumor in accordance with claim 1, wherein m=2, n=4, R₁ is H, and R₂ is CH₃.

4. A method of imaging a tumor in accordance with claim 1, wherein m=2, n=4, R₁ is H, and R₂ is Br.

5. A method of imaging a tumor in accordance with claim 1, wherein m=2, n=4, R₁ is H, and R₂ is I.

6. A method of imaging a tumor in accordance with claim 1, wherein m=2, n=4, R₁ is OCH₃, and R₂ is I.

7. A method of imaging a solid tumor in a mammal, the method comprising:

administering to the mammal a radiolabelled fluoroalkoxybenzamide compound of structure

wherein m is an integer from 1 to about 10, n is an integer from 1 to about 10, and R is selected from the group consisting of H, a halogen selected from the group consisting of I, Br, Cl and F, a C_1-4 alkoxy, a C_1-4 alkyl, a C_1-4 fluoroalkyl, a C_1-4 fluoroalkoxy, CF₃, OCF₃, SCH₃, SCF₃, and NH₂, or a salt thereof; and

subjecting the mammal to single photon emission computed tomography (SPECT) imaging.

8. A method in accordance with claim 7, wherein m=2, n=4 and R is selected from the group consisting of H and methoxy.