US 12,145,956 B2
Programmable polymeric drugs
Tracy Matray, Snohomish, WA (US); Sharat Singh, Rancho Santa Fe, CA (US); C. Frederick Battrell, Wenatchee, WA (US); and Michael Vanbrunt, Covington, WA (US)
Assigned to SONY GROUP CORPORATION, Tokyo (JP)
Appl. No. 16/639,496
Filed by SONY GROUP CORPORATION, Tokyo (JP)
PCT Filed Oct. 5, 2018, PCT No. PCT/US2018/054725
§ 371(c)(1), (2) Date Feb. 14, 2020,
PCT Pub. No. WO2019/071208, PCT Pub. Date Apr. 11, 2019.
Claims priority of provisional application 62/568,706, filed on Oct. 5, 2017.
Prior Publication US 2021/0032277 A1, Feb. 4, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07F 9/24 (2006.01); A61K 47/58 (2017.01); A61K 47/68 (2017.01); A61K 49/00 (2006.01)
CPC C07F 9/2408 (2013.01) [A61K 47/605 (2017.08); A61K 47/6809 (2017.08); A61K 47/6849 (2017.08); A61K 47/6851 (2017.08); A61K 47/6883 (2017.08); A61K 49/0043 (2013.01); A61K 49/0054 (2013.01)] 20 Claims
 
1. A compound having the following structure (IA):

OG Complex Work Unit Chemistry
or a stereoisomer, pharmaceutically acceptable salt or tautomer thereof, wherein:
M is, at each occurrence, independently a biologically active moiety selected from an NSAID, a kinase inhibitor, an anthracycline, an EGFR inhibitor, an alkylating agent, and anti-cancer drug; or a fluorescent dye, provided at least one occurrence of M is not a fluorescent dye;
L is a physiologically cleavable linker;
L2 and L3 are, at each occurrence, independently absent or an alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene or heteroatomic linker;
L4 is, at each occurrence, independently an alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene or heteroalkynylene linker;
R1 is, at each occurrence, independently H, alkyl or alkoxy;
R2 and R3 are each independently OH, SH, alkyl, alkoxy, alkylether, heteroalkyl, —OP(═Ra)(Rb)Rc, Q, or a protected form thereof, or L′;
R4 is, at each occurrence, independently OH, SH, O−, S−, ORd or SRd;
R5 is, at each occurrence, independently oxo, thioxo or absent;
Ra is O or S;
Rb is OH, SH, O−, S−, ORd or SRd;
Rc is OH, SH, O−, S−, ORd, OL′, SRd, alkyl, alkoxy, heteroalkyl, heteroalkoxy, alkylether, alkoxyalkylether, phosphate, thiophosphate, phosphoalkyl, thiophosphoalkyl, phosphoalkylether or thiophosphoalkylether;
Rd is a counter ion;
Q is, at each occurrence, independently a moiety comprising a reactive group, or protected form thereof, capable of forming a covalent bond with a complementary reactive group Q′ on a targeting moiety;
L′ is, at each occurrence, independently a linker comprising a covalent bond to Q, a targeting moiety, a linker comprising a covalent bond to a targeting moiety, a linker comprising a covalent bond to a solid support, a linker comprising a covalent bond to a solid support residue, a linker comprising a covalent bond to a nucleoside or a linker comprising a covalent bond to a further compound of structure (IA);
m is, at each occurrence, independently an integer of zero or greater; and
n is an integer of one or greater.