Peptide thiourea derivative, radioisotope labeled compound containing same, and pharmaceutical composition containing same as active ingredient for treating or diagnosing prostate cancer
The present invention relates to a peptide thiourea derivative, a pharmaceutically acceptable salt thereof, a radioisotope labeled compound comprising the same, and a pharmaceutical composition for treating or diagnosing prostate cancer comprising the same as an active ingredient. The peptide thiourea derivative of the present invention is excellent in stability in human serum when it is administered in vivo and not only binds well to PSMA expressed in prostate cancer but also inhibits excellently PSMA at a low concentration. Besides, the derivative of the invention has a high water-solubility and can be excreted through the kidney not through the bile passage so that a clear image of the tumor region of prostate cancer can be obtained. Therefore, the derivative of the present invention can be effectively used as a pharmaceutical composition for treating and diagnosing prostate cancer.
1. A compound represented by formula 1 below or a pharmaceutically acceptable salt of the same:
wherein
X is single bond;
n is an integer of 3;
Y is —N(CH 2 COOH)(CH 2 ) a CH 2 CH 2 —,
m is an integer of 1 or 2; and
a, b and c are independently an integer of 0 or 1.
2. The compound or the pharmaceutically acceptable salt of the same according to claim 1 , wherein X is single bond; and
3. A preparation method of the compound represented by formula 1 of claim 1 comprising the step of preparing the compound represented by formula 1 by reacting the compound represented by formula 2 and the compound represented by formula 3 (step 1), as shown in reaction formula 1 below:
4. A labeled compound prepared by coordinating a metallic radio-isotope to the compound represented by formula 1 of claim 1 or the pharmaceutically acceptable salt thereof.
5. The labeled compound according to claim 4 , wherein the metallic radio-isotope is 67 Ga, 68 Ga, 62 Cu, 64 Cu, 67 Cu, 111 In, 90 Y, 177 Lu, or 117m Sn.
6. A pharmaceutical composition for treating or diagnosing prostate cancer comprising the labeled compound of claim 4 as an active ingredient.
7. A radiopharmaceutical for imaging prostate cancer comprising the compound of claim 1 or the pharmaceutically acceptable salt thereof as an active ingredient.
8. A kit for treating or diagnosing prostate cancer comprising the compound of claim 1 or the pharmaceutically acceptable salt thereof.
9. The kit for treating or diagnosing prostate cancer according to claim 8 , wherein the kit contains a buffer having the pH of 1 to 9 and the concentration of 1 μM to 10 M.
10. The kit for treating or diagnosing prostate cancer according to claim 9 , wherein the buffer is acetic acid, phosphoric acid, citric acid, fumaric acid, ascorbic acid, butyric acid, succinic acid, tartaric acid, carbonic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glucaric acid, boric acid or their sodium salts or potassium salts.
11. A method of treating prostate cancer of a subject comprising administering an effective amount of the compound of claim 1 or the pharmaceutically acceptable salt thereof to the subject.
12. A method of diagnosing prostate cancer of a subject comprising administering an effective amount of the compound of claim 1 or the pharmaceutically acceptable salt thereof to the subject and detecting any absorbed compound indicative of prostate cancer tissue in the subject.