US 12,472,261 B2
Conjugated inhibitors of DNA damage response
Shaun D. Fontaine, Concord, CA (US); Brian R. Hearn, Moraga, CA (US); and Daniel V. Santi, San Francisco, CA (US)
Assigned to ProLynx LLC, San Francisco, CA (US)
Appl. No. 17/639,234
Filed by ProLynx LLC, San Francisco, CA (US)
PCT Filed Aug. 28, 2020, PCT No. PCT/US2020/048608
§ 371(c)(1), (2) Date Feb. 28, 2022,
PCT Pub. No. WO2021/041964, PCT Pub. Date Mar. 4, 2021.
Claims priority of provisional application 62/893,075, filed on Aug. 28, 2019.
Prior Publication US 2022/0331437 A1, Oct. 20, 2022
Int. Cl. A61K 47/60 (2017.01); A61K 31/4155 (2006.01); A61K 31/4745 (2006.01); A61K 31/553 (2006.01)
CPC A61K 47/60 (2017.08) [A61K 31/4155 (2013.01); A61K 31/4745 (2013.01); A61K 31/553 (2013.01)] 16 Claims
 
1. A conjugate having the formula

OG Complex Work Unit Chemistry
wherein M is PEG;
y is a number describing the number of linker-drugs L-D attached to M, wherein L is —Z*—(CH2)n—C(R4)2—CH(CH(R1)(R2)—O—C(═O)—Y—;
D is selected from the group consisting of rucaparib, talazoparib, and olaparib;
Z* is a carboxamide, carbamate, urea, oxime, thioether, or triazole;
n is 0-6;
R1 and R2 are each independently H, CN, or SO2R5, wherein R5 is optionally substituted C1-C6 alkyl, optionally substituted aryl, optionally substituted heteroaryl, or N(R6)2, wherein each R6 is independently optionally substituted C1-C6 alkyl, optionally substituted aryl, optionally substituted heteroaryl, or wherein N(R6)2 forms a ring of 4-8 atoms;
each R4 is independently H or C1-C3 alkyl or both R4 groups taken together form a 3-6 membered ring;
Y has the formula N(R7)CH2, wherein R7 is optionally substituted C1-C4 alkyl or optionally substituted aryl;
and wherein at least one of R1 and R2 is other than H.