PSMA imaging agents

Patent metadata

Field	Value
Publication number	US-12583887-B2
Application number	US-202016999541-A
Country	US
Kind code	B2
Filing date	Aug 21, 2020
Priority date	Aug 22, 2011
Publication date	Mar 24, 2026
Grant date	Mar 24, 2026

Abstract

Compounds for targeting and agents for imaging, prostate-specific membrane antigen (PSMA) are disclosed. Methods of synthesizing compounds and imaging agents, as well as methods for imaging PSMA are also disclosed. The imaging agents disclosed are suitable for PET and SPECT imaging.

First claim

We claim:

1 . A method comprising:
administering to a patient, a radio-labelled compound of Formula IV:

or a pharmaceutically acceptable salts or stereoisomers thereof,
wherein:
X 1 is CH 2 or NH;
X 14 is selected from the group consisting of C(O) and heteroaryl, wherein at least one H of the heteroaryl is substituted with NO 2 ;
X 15 is selected from the group consisting of NH, aryl, heteroaryl, cycloalkyl and heterocycloalkyl;
X 16 is at least one selected from the group consisting of

 a heteroaryl, (CH 2 ) 1-25 , wherein at least one CH 2 of (CH 2 ) 1-12 is optionally replaced with heteroaryl, CONH, and —O—; or
R 13 is selected from the group consisting of H, NO 2 , N 3 , alkyne, a protecting group, a halo and a radioisotope; or
administering to a patient, a radio-labelled compound of Formula V:

or a pharmaceutically acceptable salts or stereoisomers thereof,
wherein:
X 1 is CH 2 or NH;
X 17 s selected from the group consisting of: N and CH;
X 18 is selected from the group consisting of: (CH 2 ) 1-10 wherein at least one CH 2 of (CH 2 ) 1-10 is optionally replaced by NH, aryl, heteroaryl and wherein at least one His optionally substituted with NO 2 ; and
R 14 is selected from the group consisting of O and S; and
R 15 is selected from the group consisting of N 3 , alkyne, protecting group, halo and radioisotope;
scanning the patient using positron emission tomography or single photon emission computed tomography; and
imaging a tissue in the patient.

2 . The method of claim 1 , wherein in Formula IV, X 1 is NH.

3 . The method of claim 1 , wherein in Formula IV, X 15 is an aryl.

4 . The method of claim 1 , wherein in Formula IV, X 16 is

5 . The method of claim 1 , wherein in Formula IV, R 13 is a radioisotope.

6 . The method of claim 1 , wherein in Formula V, X 1 is CH 2 .

7 . The method of claim 1 , wherein in Formula V, X 1 is NH.

8 . The method of claim 1 , wherein in Formula V, X 17 is CH.

9 . The method of claim 1 , wherein in Formula V, X 17 is N.

10 . The method of claim 1 , wherein in Formula V, wherein one CH 2 in X 18 is replaced by an aryl.

11 . The method of claim 1 , wherein R 14 is O.

12 . The method of claim 1 , wherein R 14 is S.

13 . A compound of Formula IV:

or a pharmaceutically acceptable salt or stereoisomer thereof,
wherein:
X 1 is CH 2 or NH;
X 14 is selected from the group consisting of: C(O) and heteroaryl, wherein at least one H of the heteroaryl is substituted with NO 2 ;
X 15 is selected from the group consisting of NH, aryl, heteroaryl, cycloalkyl and heterocycloalkyl;
X 16 is at least one selected from the group consisting of:

 a heteroaryl, (CH 2 ) 1-25 , wherein at least one CH 2 of (CH 2 ) 1-12 is optionally replaced with heteroaryl, CONH, or —O—; and
R 13 is selected from the group consisting of H, NO 2 , N 3 , alkyne, a protecting group, a halo and a radioisotope.

14 . The compound, pharmaceutically acceptable salt, or stereoisomer thereof of claim 13 , wherein in Formula IV, X 1 is NH.

15 . The compound, pharmaceutically acceptable salt, or stereoisomer thereof of claim 13 , wherein in Formula IV, X 15 is an aryl.

16 . The compound, pharmaceutically acceptable salt, or stereoisomer thereof of claim 13 , wherein in Formula IV, X 16 is

17 . The compound, pharmaceutically acceptable salt, or stereoisomer thereof of claim 13 , wherein in Formula IV, R 13 is a radioisotope.

18 . The compound:

or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 10 is selected from the group consisting of radionuclide and halo.

19 . A compound of Formula V:

or a pharmaceutically acceptable salts or a stereoisomers thereof,
wherein:
X 1 is CH 2 or NH;
X 17 is selected from the group consisting of N and CH;
X 18 is selected from the group consisting of (CH 2 ) 1-10 wherein at least one CH 2 of (CH 2 ) 1-10 is optionally replaced by NH, aryl, heteroaryl, and wherein at least one His optionally substituted with NO 2 ; and
R 14 is selected from the group consisting of O and S; and
R 15 is selected from the group consisting of N 3 , alkyne, protecting group, halo and radioisotope.

20 . The compound, pharmaceutically acceptable salt, or stereoisomer thereof of claim 19 , wherein in Formula V, X 1 is CH 2 .

21 . The compound, pharmaceutically acceptable salt, or stereoisomer thereof of claim 19 , wherein in Formula V, X 1 is NH.

22 . The compound, pharmaceutically acceptable salt, or stereoisomer thereof of claim 19 , wherein in Formula V, X 17 is CH.

23 . The compound, pharmaceutically acceptable salt, or stereoisomer thereof of claim 19 , wherein in Formula V, X 17 is N.

24 . The compound, pharmaceutically acceptable salt, or stereoisomer thereof of claim 19 , wherein in Formula V, wherein one CH 2 in X 18 is replaced by an aryl.

25 . The compound pharmaceutically acceptable salt, or stereoisomer thereof of claim 19 , wherein R 14 is O.

26 . The compound, pharmaceutically acceptable salt or stereoisomer thereof of claim 19 , wherein R 14 is S.

Assignees

• Siemens Medical Solutions Usa Inc

Inventors

• Wang Eric
• Kolb Hartmuth C
• Szardenings Anna Katrin
• Liu Changhui
• Walsh Joseph C
• Chen Gang
• Sinha Anjana
• Kasi Dhanalakshmi
• Yu Chul
• Gangadharmath Umesh B
• Zhang Wei
• Zhao Tieming
• Mocharla Vani P

Classifications

• C07D249/04

  1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles · CPC title

• A61K51/0453

  having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole · CPC title

• A61K51/0497

  conjugates with a carrier being an organic compounds · CPC title

• A61K51/0402

  carboxylic acid carriers, fatty acids (amino acids A61K51/0406) · CPC title

• C07D209/48

  with oxygen atoms in positions 1 and 3, e.g. phthalimide · CPC title