Sigma-2 receptor radiotracers for imaging the proliferative status of solid tumors

• US 7,390,902 B2
• Filed: 07/30/2004
• Issued: 06/24/2008
• Est. Priority Date: 07/31/2003
• Status: Expired due to Fees

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Rowland, Douglas J. Jr., Tu, Zhude, Welch, Michael J., Mach, Robert H.
• Primary Examiner(s): Seaman; D. Margaret
• Assistant Examiner(s): Chandrakumar; Nizal S.
• Application Number:
  US10/903,771
• Publication Number:
  US 20050107398A1
• Time in Patent Office: 1,425 Days
• Field of Search: 546/86, 546/87
• 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

Novel benzamide compounds of Formula (I), Formula (II) and Formula (III, salts, water soluble salts, analogs and radiolabeled counterparts thereof as sigma-2 receptor radiotracers for imaging the proliferative status of solid tumors. A method for diagnosing a mammal for the presence of a mammalian tumor therein comprises administering to the mammal a diagnostic imaging detectable effective amount of a benzamide compound having a structure illustrated in Formula (I), Formula (II) and Formula (III) and detecting binding of the compound to a tumor in the mammal. A method for diagnostic imaging of a mammalian tissue having cell surface sigma-2 receptors comprising administering to a mammal a diagnostic imaging amount of a compound having a structure illustrated in Formula (I) Formula (II) and Formula (III) and detecting an image of a tissue having an ample cells with sigma-2 receptors.

Claims

1. A radiolabeled compound or salt thereof of Formula

2. A compound of salt thereof in accordance with claim 1, wherein the at least one radioisotope is a ³H.

3. A compound of salt thereof in accordance with claim 1, wherein the at least one radioisotope is a ¹¹C.

4. A compound or salt thereof in accordance with claim 1, wherein the compound is selected from the group consisting of:

5. A compound or salt thereof in accordance with claim 1, wherein each of A and A₁ is a methoxyl.

6. A compound or salt thereof in accordance with claim 1, wherein the compound is Compound 6

7. A compound or salt thereof in accordance with claim 1, wherein the compound is Compound 10

8. A pharmaceutical composition comprising at least one compound or salt thereof of claim 1, and a pharmaceutically acceptable carrier.

9. A radioiodinated compound or salt thereof of Formula (I)

10. A radioiodinated compound or salt thereof of in accordance with claim 9, wherein the compound has the structure

11. A radioiodinated compound or salt thereof in accordance with claim 10, wherein the compound is selected from the group consisting of

12. A radioiodinated compound or salt thereof of in accordance with claim 9, wherein the radioiodine is an ¹²³I.

13. A radioiodinated compound or salt thereof of in accordance with claim 9, wherein the radioiodine is an ¹²⁵I.

14. A radioiodinated compound or salt thereof in accordance with claim 9, wherein each of A and A₁ is a methoxyl.

15. A pharmaceutical composition comprising at least one radioiodinated compound or salt thereof of claim 9, and a pharmaceutically acceptable carrier.