US 11,931,431 B2 · PSMA-targeted radiopharmaceutical for diagnosing and treating prostate cancer

Abstract

The present invention relates to a pharmaceutical composition for diagnosing and treating prostate cancer, capable of targeting PSMA, and a compound provided by one aspect of the present invention has a glutamine-urea-lysine compound to which a radioactive metal-coupled chelator is structurally coupled and to which an aryl group that can additionally bind to PSMA protein is coupled. Coupling between the glutamine-urea-lysine compound and the chelator includes a polar spacer so as to serve the role of reducing in vivo nonspecific coupling and exhibit an effect of being rapidly removed from vital organs, but not from prostate cancer. These characteristics lower the radiation exposure, which is caused by a therapeutic radioisotope-coupled compound, to normal tissue and organs, and thus reduce side effects. In addition, a compound that contains a phenyl group having a coupling force with albumin has an increased residence time in the blood, thereby becoming more accumulated in prostate cancer.

Claims12

Dependent claims

A compound represented by formula 1, a stereoisomer thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof:

In formula 1,
L1 is —(CH2)a—, wherein a is an integer of 1 to 8;
U is a bond, or —C(O)—;
R1 is -L5-CO2H, wherein L5 is —(CH2)b—, wherein b is an integer of 1 to 6;
X is a bond, or —C(O)—;
W is a bond, or —NA1-, A1 is hydrogen, or —(CH2)c-pyridyl, wherein c is an integer of 0 to 3;
L2 is a bond, or —(CH2)d—, wherein d is an integer of 1 to 8;
Tz is a bond,
L3 is C1-12 straight or branched alkylene, wherein one or more carbon atoms in alkylene can be replaced by oxygen atoms;
L4 is —(CH2)e—, wherein e is an integer of 1 to 6;
n is an integer of 0 to 1;
R2 is hydrogen, C1-5 straight or branched alkyl, or halogen;
Y is oxygen or sulfur;
Z is a chelator including a radioactive metal, wherein the radioactive metal is Ga-68, Cu-64, Cu-67, Y-90, Sc-47, In-111, Sn-117m, Lu-177, Bi-212, Bi-213, Pb-212, Ra-223, or Ac-225, and the chelator is

11 more elements

A compound represented by formula 2, a stereoisomer thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof:

wherein in formula 2,
L1 is —(CH2)a—, wherein a is an integer of 1 to 8;
U is a bond, or —C(O)—;
R1 is -L5-CO2H, wherein L5 is —(CH2)b—, wherein b is an integer of 1 to 6;
X is a bond, or —C(O)—;
W is a bond or —NA1-, and A1 is hydrogen or —(CH2)c-pyridyl, wherein c is an integer of 0 to 3;
L2 is a bond or —(CH2)d—, wherein d is an integer of 1 to 8;
Tz is a bond,
L3 is C1-12 straight or branched alkylene, wherein one or more carbon atoms in alkylene can be replaced by oxygen atoms;
L4 is —(CH2)e—, wherein e is an integer of 1 to 6;
n is an integer of 0 to 1;
R2 is hydrogen, C1-5 straight or branched alkyl, or halogen;
Y is oxygen or sulfur;
Z′ is a chelator, and the chelator is

11 more elements

Dependencies are inferred from the claim text.

PSMA-targeted radiopharmaceutical for diagnosing and treating prostate cancer

Life of this patent

PSMA-targeted radiopharmaceutical for diagnosing and treating prostate cancer

Life of this patent

Abstract

Claims12