18f-labeled triazole containing psma inhibitors

Patent metadata

Field	Value
Publication number	US-2022194904-A1
Application number	US-202117390284-A
Country	US
Kind code	A1
Filing date	Jul 30, 2021
Priority date	Jun 28, 2016
Publication date	Jun 23, 2022
Grant date	—

Abstract

The present technology is directed to compounds, intermediates thereof, compositions thereof, medicaments thereof, and methods related to the imaging of mammalian tissue overexpressing PSMA. The compounds are of Formula I

or a pharmaceutically acceptable salt thereof, wherein one of R 1 , R 2 , and R 3 is

and of Formula IV

or a pharmaceutically acceptable salt thereof.

First claim

What is claimed is:

1 . A compound of Formula I

or a pharmaceutically acceptable salt thereof, wherein
P 1 , P 2 , and P 3 are each independently H, methyl, benzyl, 4-methoxybenzyl, or tert-butyl;
W 1 is —C(O)— or —(CH 2 ) n —NH 2 —C(O)—;
one of R 1 , R 2 , and R 3 is

and the remaining two of R 1 , R 2 , and R 3 are each H;
X 1 is absent, O, S, or NH; m is 0, 1, 2, or 3; n is 1 or 2; p is 0, 1, 2, or 3, provided that when p is 0 then X 1 is absent; and q is 1 or 2.

2 . The compound of claim 1 , wherein P 1 , P 2 , and P 3 are each independently H or tert-butyl.

3 . The compound of claim 1 , wherein P 1 , P 2 , and P 3 are each independently H.

4 . An intermediate for preparing a compound of claim 1 , wherein the intermediate is of Formula II

wherein
P 4 , P 5 , and P 6 are each independently H, methyl, benzyl, 4-methoxybenzyl, or tert-butyl;
W 2 is —C(O)— or —(CH 2 ) s —NH 2 —C(O)—;
one of R 4 , R 5 , and R 6 is

and the remaining two of R 4 , R 5 , and R 6 are each H;
X 2 is absent, O, S, or NH; r is 0, 1, 2, or 3; s is 1 or 2; and t is 0, 1, 2, or 3, provided that when t is 0 then X 2 is absent.

5 . A composition comprising a compound of claim 3 and a pharmaceutically acceptable carrier.

6 . A pharmaceutical composition for detecting mammalian tissue overexpressing prostate specific membrane antigen (“PSMA”), the composition comprising an effective amount of the compound of claim 3 and a pharmaceutically acceptable carrier.

7 . The pharmaceutical composition of claim 6 , wherein the mammalian tissue comprises one or more of glioma, cervical carcinoma, vulvar carcinoma, endometrial carcinoma, primary ovarian carcinoma, metastatic ovarian carcinoma, non-small cell lung cancer, small cell lung cancer, bladder cancer, colon cancer, primary, gastric adenocarcinoma, primary colorectal adenocarcinoma, renal cell carcinoma, and prostate cancer.

8 . A method comprising
administering a compound of claim 3 to a subject; and subsequent to the administering, detecting one or more of positron emission, gamma rays from positron emission and annihilation, and Cerenkov radiation due to positron emission.

9 . The method of claim 8 , wherein the method comprises administering an effective amount of the compound to the subject.

10 . The method of claim 8 , wherein the subject is suspected of suffering from a mammalian tissue overexpressing prostate specific membrane antigen (“PSMA”).

11 . The method of claim 10 , wherein the mammalian tissue comprises one or more of glioma, cervical carcinoma, vulvar carcinoma, endometrial carcinoma, primary ovarian carcinoma, metastatic ovarian carcinoma, non-small cell lung cancer, small cell lung cancer, bladder cancer, colon cancer, primary, gastric adenocarcinoma, primary colorectal adenocarcinoma, renal cell carcinoma, and prostate cancer.

12 . The method of claim 8 , wherein the administering the compound comprises parenteral administration.

13 . A compound of Formula IV

wherein
P 7 , P 8 , and P 9 are each independently H, methyl, benzyl, 4-methoxybenzyl, or tert-butyl;
w is 1 or 2;
x is 0, 1, 2, or 3; and
y is 1 or 2.

14 . The compound of claim 13 , wherein P 7 , P 8 , and P 9 are each independently H or tert-butyl.

15 . The compound of claim 13 , wherein P 7 , P 8 , and P 9 are each independently H.

16 . An intermediate for preparing a compound of claim 13 , wherein the intermediate is of Formula V

wherein
P 10 , P 11 , and P 12 are each independently H, methyl, benzyl, 4-methoxybenzyl, or tert-butyl;
b is 1 or 2; and
d is 0, 1, 2, or 3.

17 . A composition comprising a compound of claim 15 and a pharmaceutically acceptable carrier.

18 . A pharmaceutical composition for detecting a mammalian tissue overexpressing prostate specific membrane antigen (“PSMA”), the composition comprising an effective amount of the compound of claim 15 and a pharmaceutically acceptable excipient.

19 . A method comprising
administering a compound of claim 15 to a subject; and subsequent to the administering, detecting one or more of positron emission, gamma rays from positron emission and annihilation, and Cerenkov radiation due to positron emission.

20 . The method of claim 19 , wherein the method comprises administering an effective amount of the compound to the subject.

Assignees

• Univ Cornell

Inventors

• Babich John W
• Kelly Jasmes M
• Amor-Coarasa Alejandro
• Ponnala Shashikanth

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K51/0497 Primary

  conjugates with a carrier being an organic compounds · CPC title

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• A61B6/032

  Transmission computed tomography [CT] · CPC title

• C07C275/16

  being further substituted by carboxyl groups · CPC title