Cholecystokinin B receptor targeting for imaging and therapy

Patent metadata

Field	Value
Publication number	US-10765756-B2
Application number	US-201816105734-A
Country	US
Kind code	B2
Filing date	Aug 20, 2018
Priority date	Feb 24, 2012
Publication date	Sep 8, 2020
Grant date	Sep 8, 2020

Abstract

Conjugates are described herein where CCK2R targeting ligands are attached to an active moiety, such as therapeutic agent or an imaging agent, through a linker. The conjugates can be used in the detection, diagnosis, imaging and treatment of cancer.

First claim

What is claimed is:

1. A conjugate of the formula
B-L-D

wherein
B is a targeting ligand of Formula I

L is a bivalent or polyvalent linker; and
D is an optical dye; or a pharmaceutically acceptable salt thereof.

2. The conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the optical dye is of Formula II

wherein
X is selected from the group consisting of oxygen, nitrogen, and sulfur, and X is attached to the linker L;
Y is selected from the group consisting of OR a , NR a 2 , and NRa 3 + ;
Y′ is selected from the group consisting of O, NR a , and NR a 2 + ;
each R is independently selected from the group consisting of H, fluoro, sulfonic acid, sulfonate, and salts thereof; and
R a is hydrogen or alkyl.

3. The conjugate of claim 2 , or a pharmaceutically acceptable salt thereof, wherein X is nitrogen.

4. The conjugate of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R is H.

5. The conjugate of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R a is hydrogen.

6. The conjugate of claim 2 , or a pharmaceutically acceptable salt thereof, wherein Y′ is O.

7. The conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the optical dye is of Formula III

wherein X is selected from the group consisting of oxygen, nitrogen, and sulfur, and X is attached to linker L.

8. The conjugate of claim 7 , or a pharmaceutically acceptable salt thereof, wherein X is nitrogen.

9. The conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the optical dye is selected from the group consisting of fluorescein (FITC), rhodamine, S0456, IR800CW, and LS288.

10. The conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the linker L is a non-releasable linker.

11. The conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the linker L comprises one or more amino acids.

12. The conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the linker L comprises glutamic acid.

13. The conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the linker L comprises a carbamate moiety.

14. The conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the linker L is L1, L2 or L3
L1: HN-Glu-Arg-Asp-CO
L2: HN-Glu-PS-Glu-PS-CO
L3: HN-Octanoyl-Glu-PS-Glu-PS-CO

wherein PS is of the formula

15. A conjugate of the formula

Assignees

• Purdue Research Foundation

Inventors

• Low Philip S
• Wayua Charity

Classifications

• A61K51/0468

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• A61K38/07

  Tetrapeptides · CPC title

• A61K31/4409

  only substituted in position 4, e.g. isoniazid, iproniazid · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D243/12

  1,5-Benzodiazepines; Hydrogenated 1,5-benzodiazepines · CPC title