Radiolabeled prostate specific membrane antigen inhibitors

• US 8,926,944 B2
• Filed: 08/03/2012
• Issued: 01/06/2015
• Est. Priority Date: 08/05/2011
• Status: Active Grant

• Current Assignee: Molecular Insight Pharmaceuticals Incorporated (Lantheus Holdings, Inc.)
• Original Assignee: Molecular Insight Pharmaceuticals Incorporated (Lantheus Holdings, Inc.)
• Inventors: Babich, John W., Zimmerman, Craig, Joyal, John L., Lu, Genliang
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): SAMALA, JAGADISHWAR RAO
• Application Number:
  US13/566,849
• Publication Number:
  US 20130034494A1
• Time in Patent Office: 886 Days
• Field of Search: 424/1.1, 424/1.65, 424/1.85, 424/1.89, 424/9.1, 514/120, 514/121
• US Class Current: 424/1.65
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 51/0402 carboxylic acid carriers, fatty acids amino acids A61K51/0406
• CPC Class Codes: A61K 51/0478 complexes from non-cyclic ligands, e.g. EDTA, MAG3
• CPC Class Codes: A61K 51/0482 chelates from cyclic ligands, e.g. DOTA
• 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: C07D 255/02 not condensed with other rings
• CPC Class Codes: C07D 257/02 not condensed with other rings
• CPC Class Codes: C07D 403/14 containing three or more hetero rings
• CPC Class Codes: C07F 5/003 without C-Metal linkages

Abstract

Compounds according to Formula I and Formula II are potent inhibitors of PSMA activity:

The invention also provides pharmaceutical compositions of a complex of a radionuclide and a Formula I compound or a Formula II compound and methods of using the radionuclide complex of a Formula I compound or a Formula II compound for treating or diagnosis of a disease or a condition associated with PSMA activity.

Claims

1. A compound represented by formula II

2. The compound of claim 1, which is:

3. A metal complex comprising a radionuclide and the compound of claim 1.

4. The metal complex of claim 3, wherein the radionuclide is ¹¹¹In, ⁹⁰Y, ⁶⁸Ga, ⁶⁴Cu ¹⁵³Gd, ¹⁵⁵Gd, ¹⁵⁷Gd, Fe or ¹⁷⁷Lu.

5. The metal complex of claim 3, which is:

6. The compound of claim 1, wherein any aryl, arylalkylene, benzyl, heteroaryl, or cycloalkyl group is substituted with 1, 2, or 3 substituent groups selected from the group consisting of:

—

(C₁-C₁₀)alkyl, halogen, —

(C₁-C₁₀)haloalkyl, —

(C₁-C₁₀)aminoalkyl, —

(C₁-C₁₀)hydroxyalkyl, —

(CH₂)_p—

C(O)—

U and —

(C₃-C₈)cycloalkyl.

7. A pharmaceutical composition comprising the compound of claim 1 or the metal complex of claim 5, or a pharmaceutically acceptable salt, solvate, or ester thereof;

and a pharmaceutically acceptable carrier.