US 11,766,433 B2
Small molecule inhibitors of the nuclear translocation of androgen receptor for the treatment of castration-resistant prostate cancer
Peter Wipf, Pittsburgh, PA (US); James K. Johnson, Silver Spring, MD (US); Erin M. Skoda, Silver Spring, MD (US); Joel B. Nelson, Pittsburgh, PA (US); Zhou Wang, Pittsburgh, PA (US); Serene Tai, Pittsburgh, PA (US); Keita Takubo, Pittsburgh, PA (US); and John Milligan, Philadelphia, PA (US)
Assigned to University of Pittsburgh - Of the Commonwealth System of Higher Education, Pittsburgh, PA (US)
Filed by University of Pittsburgh - Of the Commonwealth System of Higher Education, Pittsburgh, PA (US)
Filed on Nov. 4, 2020, as Appl. No. 17/89,519.
Application 17/089,519 is a continuation of application No. 16/139,950, filed on Sep. 24, 2018, granted, now 10,980,806.
Application 16/139,950 is a continuation in part of application No. PCT/US2017/024105, filed on Mar. 24, 2017.
Application PCT/US2017/024105 is a continuation in part of application No. 15/080,237, filed on Mar. 24, 2016, abandoned.
Claims priority of provisional application 62/671,254, filed on May 14, 2018.
Prior Publication US 2021/0186963 A1, Jun. 24, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/495 (2006.01); A61K 31/504 (2006.01); A61K 31/4985 (2006.01); A61K 31/497 (2006.01); A61K 31/4439 (2006.01); A61K 31/401 (2006.01); A61K 31/407 (2006.01); A61K 31/122 (2006.01); A61K 31/47 (2006.01); A61K 9/00 (2006.01); A61P 35/00 (2006.01); A61K 31/167 (2006.01); A61K 31/4166 (2006.01); A61K 31/58 (2006.01)
CPC A61K 31/504 (2013.01) [A61K 9/0053 (2013.01); A61K 31/122 (2013.01); A61K 31/167 (2013.01); A61K 31/401 (2013.01); A61K 31/407 (2013.01); A61K 31/4439 (2013.01); A61K 31/47 (2013.01); A61K 31/497 (2013.01); A61K 31/4985 (2013.01); A61P 35/00 (2018.01); A61K 31/4166 (2013.01); A61K 31/58 (2013.01); A61K 2300/00 (2013.01)] 16 Claims
 
1. A compound, or a stereoisomer, pharmaceutically acceptable salt, or ester thereof, selected from:
a compound according to formula III

OG Complex Work Unit Chemistry
where the bond represented by “-----” is a single or double bond,
R20 is (a) phenyl substituted with C1-C3 perfluoroalkyl, halo, or pentafluorosulfanyl,
(b) thiophenyl substituted with C1-C3 alkyl, or (c) cycloalkyl substituted with C1-C3 perfluoroalkyl,
R23 is (a) phenyl mono- or di-substituted with substituents selected from halo, C1-C3 alkyl, C1-C3 perfluoroalkyl, pentafluorosulfanyl, cyano, —C(O)Oalkyl, or —C(O)N(H)alkyl, (b) cycloalkyl, or
(c) heterocycloalkyl,
R24 and R25 are absent if the bond represented by “-----” is a double bond, or R24 and R25 independently are hydrogen, deuterium, C1-C3 perhaloalkyl, halo, or cyano, or R24 and R25 together form —CH2—, and
R26 and R27 independently are hydrogen, deuterium, or halo,
wherein if R24-R27 are hydrogen, then R20 is not halo-substituted phenyl, and
if R24-R27 are hydrogen and R23 is phenyl mono- or di-substituted with substituents selected from halo, C1-C3 alkyl, C1-C3 perfluoroalkyl, pentafluorosulfanyl, cyano, —C(O)Oalkyl, or —C(O)N(H)alkyl, then R20 is (a) pentafluorosulfanyl-substituted phenyl, (b) thiophenyl substituted with C1-C3 alkyl, or (c) cycloalkyl substituted with C1-C3 perfluoroalkyl.