Heterodimers of glutamic acid

• US 9,309,193 B2
• Filed: 10/12/2011
• Issued: 04/12/2016
• Est. Priority Date: 11/08/2006
• 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 N., Maresca, Kevin P.
• Primary Examiner(s): Sznaidman, Marcos
• Assistant Examiner(s): Rodriguez, Rayna B
• Application Number:
  US13/271,549
• Publication Number:
  US 20120269726A1
• Time in Patent Office: 1,644 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 39/385 Haptens or antigens, bound to carriers
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07B 59/001 Acyclic or carbocyclic compounds
• CPC Class Codes: C07C 275/16 being further substituted by carboxyl groups
• CPC Class Codes: C07C 275/24 containing six-membered aromatic rings
• CPC Class Codes: C07C 275/30 being further substituted by halogen atoms, or by nitro or nitroso groups
• CPC Class Codes: C07C 311/19 to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
• CPC Class Codes: C07D 213/38 having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom

Abstract

Compounds of Formula (Ia)

• wherein R is a C₆-C₁₂ substituted or unsubstituted aryl, a C₆-C₁₂ substituted or unsubstituted heteroaryl, a C₁-C₆ substituted or unsubstituted alkyl or —NR′R′,
• Q is C(O), O, NR′, S, S(O)₂, C(O)₂ (CH2)p
• Y is C(O), O, NR′, S, S(O)₂, C(O)₂ (CH2)p
• Z is H or C₁-C₄ alkyl,
• R′ is H, C(O), S(O)₂, C(O)₂, a C₆-C₁₂ substituted or unsubstituted aryl, a C₆-C₁₂ substituted or unsubstituted heteroaryl or a C₁-C₆ substituted or unsubstituted alkyl, when substituted, aryl, heteroaryl and alkyl are substituted with halogen, C₆-C₁₂ heteroaryl, —NR′R′ or COOZ, which have diagnostic and therapeutic properties, such as the treatment and management of prostate cancer and other diseases related to NAALADase inhibition. Radiolabels can be incorporated into the structure through a variety of prosthetic groups attached at the X amino acid side chain via a carbon or hetero atom linkage.

Claims

1. A method of imaging one or more organs or tissues or both of a mammal comprising:

(A) administering to a mammal an effective amount of a compound of Formula (I)

2. The method of claim 1, wherein the one or more organs or tissues or both includes prostate, prostate tissue or prostate cancer tissue, kidney tissue, brain tissue, vascular tissue, or tumor tissue.

3. The method of claim 1, wherein

n is 0 or 1;

m is 4;

Y is C(O) or CH₂; and

R is a phenyl moiety substituted with a radiohalogen.

4. The method of claim 1, wherein the compound is:

5. The method of claim 1, wherein the compound is:

6. The method of claim 1, wherein the compound is of the Formula (II):

7. The method of claim 1, wherein the compound is of Formula Iib:

8. The method of claim 1, wherein the compound is of the following structure:

9. The method of claim 1, wherein the compound is selected from the group consisting of:

10. The method of claim 1, wherein the compound is selected from the group consisting of:

11. The method of claim 1, wherein the compound is selected from the group consisting of:

12. The method of claim 1, wherein the radiohalogen is an imaging radiohalogen or a therapeutic radiohalogen.

13. The method of claim 8 having the formula:

14. The method of claim 1, wherein the compound is of the following structure:

15. The method of claim 1, wherein the compound is of the following structure:

16. A method of imaging one or more organs or tissues or both of a mammal comprising administering to a mammal an effective amount of a compound having the formula:

17. A method of imaging one or more organs or tissues or both of a mammal comprising:

(A) administering to a mammal an effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein the compound is

18. The method of claim 17, wherein the one or more organs or tissues or both includes prostate, prostate tissue or prostate cancer tissue, kidney tissue, brain tissue, vascular tissue, or tumor tissue.

19. The method of claim 17, wherein the compound is administered in a pharmaceutically effective dosage.