US 12,246,069 B2
Method of making prodrug for sustained and controlled release
Joo-Youp Lee, Cincinnati, OH (US); Edward Merino, Cincinnati, OH (US); Vishnu Sriram, Cincinnati, OH (US); and Mina Jafari, Cincinnati, OH (US)
Assigned to University of Cincinnati, Cincinnati, OH (US)
Appl. No. 17/442,949
Filed by University of Cincinnati, Cincinnati, OH (US)
PCT Filed Mar. 26, 2020, PCT No. PCT/US2020/024881
§ 371(c)(1), (2) Date Sep. 24, 2021,
PCT Pub. No. WO2020/198431, PCT Pub. Date Oct. 1, 2020.
Prior Publication US 2022/0184219 A1, Jun. 16, 2022
Int. Cl. A61K 47/59 (2017.01); A61K 47/54 (2017.01); A61K 47/60 (2017.01); A61P 35/00 (2006.01)
CPC A61K 47/593 (2017.08) [A61K 47/54 (2017.08); A61K 47/60 (2017.08); A61P 35/00 (2018.01)] 22 Claims
 
1. A compound of the formula:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or solvate thereof, wherein, independently for each occurrence:
X is NH or O;
Y is O, S, or NR2;
Z is OH, OR2, NHR2, or SR2;
R1 is a chemotherapeutic agent selected from the group consisting of alkylating agents;
purine and pyrimidine analogs and derivatives; topoisomerase inhibitors; taxanes;
antifolates; angiogenesis inhibitors; anti-tumor monoclonal antibodies; cytotoxic antibiotics; anthracycline antibiotics; triterpenoid Stat3 inhibitors; and physiologically acceptable salts thereof; and
R2 is a polymer selected from the group consisting of poly-L-lactic acid-polyethylene glycol (PLLA-PEG), poly-D,L-lactic acid-polyethylene glycol (PDLLA-PEG), poly(lactide-co-glycolide)-polyethylene glycol (PLGA-PEG), Poly (L-aspartic acid), Poly (L-lysine), Poly (L-glutamic acid), Poly (L-arginine), and Poly (L-ornithine); or R2 is a linkage to said polymer.