US 11,925,696 B2
Carbonic anhydrase IX targeting agents and methods
Philip S. Low, West Lafayette, IN (US); and Pengcheng Lu, Hoover, AL (US)
Assigned to Purdue Research Foundation, West Lafayette, IN (US)
Appl. No. 16/085,393
Filed by Purdue Research Foundation, West Lafayette, IN (US)
PCT Filed Mar. 16, 2017, PCT No. PCT/US2017/022785
§ 371(c)(1), (2) Date Sep. 14, 2018,
PCT Pub. No. WO2017/161170, PCT Pub. Date Sep. 21, 2017.
Claims priority of provisional application 62/309,264, filed on Mar. 16, 2016.
Claims priority of provisional application 62/309,268, filed on Mar. 16, 2016.
Prior Publication US 2019/0083663 A1, Mar. 21, 2019
Int. Cl. A61K 51/04 (2006.01); A61K 47/60 (2017.01); A61K 47/65 (2017.01); A61K 49/00 (2006.01)
CPC A61K 51/0497 (2013.01) [A61K 47/60 (2017.08); A61K 47/65 (2017.08); A61K 49/0032 (2013.01); A61K 49/0041 (2013.01); A61K 51/04 (2013.01); A61K 2123/00 (2013.01)] 10 Claims
 
1. A conjugate of the formula B-L-A, wherein B is a binding ligand of carbonic anhydrase IX (CA IX) having the formula

OG Complex Work Unit Chemistry
wherein
wherein each R6 and R7 is independently selected from the group consisting of H, OR9, —OC(O)R9, —OC(O)NR9R10, —OS(O)R9, —OS(O)2R9, —SR9, —S(O)R9, —S(O)2R9, —S(O)NR9R10, S(O)2NR9R10, —OS(O)NR9R10, —OS(O)2NR9R10, —NR9R10, —NR9C(O)R10, —NR9C(O)OR10, —NR9C(O)NR9R10, —NR9S(O)R10, —NR9S(O)2R10, —NR9S(O)NR9R10, —NR9S(O)2NR9R10, —C(O)R9, —C(O)OR9, and —C(O)NR9R10;
R8 is selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl, —C(O)R11, —C(O)OR11, and —C(O)NR11R12;
Y is —NR9′—;
Z is —NR10′—;
each R9, R10, R9′, R10′ R11 and R12 is independently selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
p is an integer from 1 to 4;
r is an integer from 0 to 4;
t is an integer from 1 to 3; and
* represents a covalent bond to L;
wherein L is a linker of 2 to 100 atoms in length covalently attached to B and A, and
wherein A is a therapeutic agent, or an imaging agent selected from a rhodamine dye and a single-photon emission computed tomography (SPECT) imaging agent, and A is covalently attached to L.