US 12,290,571 B2
Programmable dendritic drugs
Tracy Matray, Snohomish, WA (US); and Hesham Sherif, Redmond, WA (US)
Assigned to Sony Group Corporation, Tokyo (JP)
Appl. No. 16/639,499
Filed by SONY GROUP CORPORATION, Tokyo (JP)
PCT Filed Oct. 5, 2018, PCT No. PCT/US2018/054648
§ 371(c)(1), (2) Date Feb. 14, 2020,
PCT Pub. No. WO2019/071153, PCT Pub. Date Apr. 11, 2019.
Claims priority of provisional application 62/568,681, filed on Oct. 5, 2017.
Prior Publication US 2020/0222554 A1, Jul. 16, 2020
Int. Cl. A61K 47/68 (2017.01); A61K 47/54 (2017.01); A61K 47/59 (2017.01)
CPC A61K 47/6889 (2017.08) [A61K 47/545 (2017.08); A61K 47/59 (2017.08); A61K 47/6801 (2017.08)] 16 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 non-steroidal anti-inflammatory drug (NSAID), a kinase inhibitor, an anthracycline, an epidermal growth factor receptor (EGFR) inhibitor, an alkylating agent, and an anti-cancer drug, or a fluorescent dye, provided at least one occurrence of M is not a fluorescent dye;
L1 and L2 are, at each occurrence, independently an alkylene, heteroalkylene, or heteroatomic linker, wherein the heteroatomic linker is one or more heteroatoms;
L4 is, at each occurrence, independently an alkylene or heteroalkylene, or absent;
L5 is, at each occurrence, independently an alkylene or absent;
L6 is, at each occurrence, independently a linker comprising an amide bond, an ester bond, a disulfide bond, a double bond, a triple bond, an ether bond, a ketone, a diol, a cyano, a nitro or combinations thereof;
L7 and L8 are, at each occurrence, independently an alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene or heteroalkynylene linker;
R1 is, at each occurrence, independently H, alkyl or alkoxy;
R2 is —OP(═Ra)(Rb)Rc;
R3 is, at each occurrence, independently OH, —OP(═Ra)(Rb)Rc, Q or has the following structure:

OG Complex Work Unit Chemistry
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;
R4 is, at each occurrence, independently OH, SH, O−, S−, ORd or SRd;
R5 is, at each occurrence, independently oxo, thioxo or absent;
Q is, at each occurrence, independently a moiety having one of the following structures:

OG Complex Work Unit Chemistry

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wherein:
each X is independently a halogen; and
EWG is an electron withdrawing group;
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), wherein the targeting moiety is an antibody or cell surface receptor antagonist;
L2′ is, at each occurrence, independently a direct bond, an optional alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene or heteroatomic linker;
L3 is, at each occurrence, independently an alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene linker, or absent;
n is, at each occurrence, independently an integer of one or greater;
m is, at each occurrence, independently an integer of one or greater;
p is, at each occurrence, independently an integer of one to ten; and
q is, at each occurrence, independently an integer of zero or greater;
wherein R2 or at least one of occurrence of R3 has the following structure:

OG Complex Work Unit Chemistry