US 12,319,681 B2
Tripartite androgen receptor eliminators, methods and uses thereof
Zory Shaposhnik, Northridge, CA (US)
Assigned to SPG Therapeutics, Inc., Northridge, CA (US)
Filed by SPG Therapeutics, Inc., Northridge, CA (US)
Filed on Sep. 13, 2022, as Appl. No. 17/931,773.
Application 17/931,773 is a division of application No. 16/608,749, granted, now 11,447,483, previously published as PCT/US2018/030538, filed on May 1, 2018.
Claims priority of provisional application 62/492,822, filed on May 1, 2017.
Prior Publication US 2023/0092979 A1, Mar. 23, 2023
Int. Cl. C07D 417/14 (2006.01); C07C 43/196 (2006.01); C07C 53/138 (2006.01); C07C 69/708 (2006.01); C07C 233/21 (2006.01); C07D 405/14 (2006.01); C07D 417/12 (2006.01); C07J 71/00 (2006.01)
CPC C07D 417/14 (2013.01) [C07C 43/196 (2013.01); C07C 53/138 (2013.01); C07C 69/708 (2013.01); C07C 233/21 (2013.01); C07D 405/14 (2013.01); C07D 417/12 (2013.01); C07J 71/0005 (2013.01)] 19 Claims
 
1. A compound of formula (I),
ARA-L-EE  (I)
wherein
ARA is an androgen receptor (AR) antagonist that is spironolactone
having the following structure:

OG Complex Work Unit Chemistry
L is a linker molecule of formula (III), (IV), (V), (VI), (VII), (VIII), (IX) or (X):

OG Complex Work Unit Chemistry
wherein each n is independently any integer from 0 to 10;
and
EE is an E3 ligase-recruiting moiety selected from the group consisting of a nutlin moiety, a bestatin moiety, a phthalimide moiety, and a moiety according to formula (XII):

OG Complex Work Unit Chemistry
wherein R8 is OH, COOH, NH2, a halogen, R9OH, R9COOH, ROC(O) NH2 or R6C(O) R10,
wherein R9 is C1-10 alkyl, C2-10 alkenyl, or C2-10 alkynyl, and R10 is a halogen;
wherein ARA is conjugated to EE via the linker molecule, and wherein the linker molecule is covalently attached to each of ARA and EE.