US 12,295,939 B2
Substituted benzothiophene analogs as selective estrogen receptor degraders
Gregory R Thatcher, Tucson, AZ (US); Rui Xiong, Chicago, IL (US); Jiong Zhao, Chicago, IL (US); Yunlong Lu, Chicago, IL (US); Lauren Gutgesell, Chicago, IL (US); Carlo Ivan Rosales, Chicago, IL (US); and Yangfeng Li, Chicago, IL (US)
Assigned to The Board of Trustees of the University of Illinois, Urbana, IL (US)
Filed by The Board of Trustees of the University of Illinois, Urbana, IL (US)
Filed on Aug. 3, 2023, as Appl. No. 18/364,621.
Application 18/364,621 is a division of application No. 16/967,188, granted, now 11,759,450, previously published as PCT/US2019/016793, filed on Feb. 6, 2019.
Claims priority of provisional application 62/657,046, filed on Apr. 13, 2018.
Claims priority of provisional application 62/626,785, filed on Feb. 6, 2018.
Prior Publication US 2023/0381137 A1, Nov. 30, 2023
Int. Cl. A61K 31/397 (2006.01); A61K 31/138 (2006.01); A61K 31/167 (2006.01); A61K 31/277 (2006.01); A61K 31/4025 (2006.01); A61K 31/4196 (2006.01); A61K 31/4535 (2006.01); A61K 31/565 (2006.01); A61K 31/566 (2006.01); A61K 31/573 (2006.01); A61K 38/09 (2006.01); A61K 39/395 (2006.01); A61K 45/06 (2006.01); C07D 409/12 (2006.01)
CPC A61K 31/397 (2013.01) [A61K 31/138 (2013.01); A61K 31/167 (2013.01); A61K 31/277 (2013.01); A61K 31/4025 (2013.01); A61K 31/4196 (2013.01); A61K 31/4535 (2013.01); A61K 31/565 (2013.01); A61K 31/566 (2013.01); A61K 31/573 (2013.01); A61K 38/09 (2013.01); A61K 39/3955 (2013.01); A61K 45/06 (2013.01); C07D 409/12 (2013.01); C07B 2200/05 (2013.01)] 15 Claims
 
1. A method for the treatment of breast cancer in a mammal comprising the step of administering to the mammal a therapeutically effective amount of a compound having a structure represented by a formula:

OG Complex Work Unit Chemistry
wherein m is selected from 0 and 1;
wherein p is selected from 0, 1, and 2;
wherein q is selected from 0, 1, and 2;
wherein each of Z1 and Z2 is independently selected from —CH— or —N—; provided Z1 and Z2 are not simultaneously —CH— or —N—; and provided when Z1 is —CH— and m is 1, that p and q are not both 0;
wherein Z10 is selected from —O— or —NH;
wherein Z11 is, when present, —CH2CH2;
wherein Z40 is —(CH2)n—, wherein n is selected from 1, 2, 3, or 4;
wherein each of R10a and R10b are independently selected from hydrogen, deuterium, halogen, and C1-C3 methyl;
wherein R is C1-C6 alkyl, C1-C6 haloalkyl, halogen, or hydroxy; and
r is 0, 1, 2, 3, or 4;
or a pharmaceutically acceptable salt thereof.