US 12,378,220 B2
WNT signaling pathway inhibitors for treatments of disease
Fengtian Xue, Potomac, MD (US); and Yan Shu, Clarksville, MD (US)
Assigned to University of Maryland, Baltimore, Baltimore, MD (US)
Filed by University of Maryland, Baltimore, Baltimore, MD (US)
Filed on May 19, 2023, as Appl. No. 18/320,805.
Application 18/320,805 is a continuation of application No. 16/900,616, filed on Jun. 12, 2020, granted, now 11,655,233.
Application 16/900,616 is a continuation of application No. 16/081,657, granted, now 10,882,841, issued on Jan. 5, 2021, previously published as PCT/US2017/020224, filed on Mar. 1, 2017.
Claims priority of provisional application 62/352,634, filed on Jun. 21, 2016.
Claims priority of provisional application 62/301,882, filed on Mar. 1, 2016.
Claims priority of provisional application 62/301,863, filed on Mar. 1, 2016.
Prior Publication US 2024/0208927 A1, Jun. 27, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 401/12 (2006.01); A61K 31/353 (2006.01); A61K 31/4184 (2006.01); A61K 31/422 (2006.01); A61K 31/4245 (2006.01); A61K 31/427 (2006.01); A61K 31/4439 (2006.01); A61K 31/4725 (2006.01); A61K 31/497 (2006.01); A61K 31/5377 (2006.01); A61K 31/541 (2006.01); A61P 1/16 (2006.01); A61P 3/10 (2006.01); A61P 35/00 (2006.01); C07D 207/34 (2006.01); C07D 207/416 (2006.01); C07D 231/14 (2006.01); C07D 249/06 (2006.01); C07D 401/14 (2006.01); C07D 403/12 (2006.01); C07D 405/12 (2006.01); C07D 413/12 (2006.01); C07D 413/14 (2006.01); C07D 417/12 (2006.01); C07D 417/14 (2006.01)
CPC C07D 401/12 (2013.01) [A61K 31/353 (2013.01); A61K 31/4184 (2013.01); A61K 31/422 (2013.01); A61K 31/4245 (2013.01); A61K 31/427 (2013.01); A61K 31/4439 (2013.01); A61K 31/4725 (2013.01); A61K 31/497 (2013.01); A61K 31/5377 (2013.01); A61K 31/541 (2013.01); A61P 1/16 (2018.01); A61P 3/10 (2018.01); A61P 35/00 (2018.01); C07D 207/34 (2013.01); C07D 207/416 (2013.01); C07D 231/14 (2013.01); C07D 249/06 (2013.01); C07D 401/14 (2013.01); C07D 403/12 (2013.01); C07D 405/12 (2013.01); C07D 413/12 (2013.01); C07D 413/14 (2013.01); C07D 417/12 (2013.01); C07D 417/14 (2013.01)] 9 Claims
 
1. A method of treating or preventing a disease alleviated by inhibiting Wnt/β-catenin signaling in a patient in need of said treatment or prevention, the method comprising administering a therapeutically effective amount of one or more compounds having the formula (II):

OG Complex Work Unit Chemistry
wherein R7 represents a substituent selected from the group consisting of substituted or unsubstituted isoquinolin-3-yl, quinolin-2-yl, quinolin-3-yl, naphthyl, thiazolyl, isooxazolyl, benzothiazolyl, benzimidizolyl, benzopyronyl,

OG Complex Work Unit Chemistry
R8 represents a substituent selected from the group consisting of H, OH, NO2, CN, halo, and substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, amino, and alkoxy;
R9, R10, R11, R12, and R13 each can independently represent a substituent selected from the group consisting of H, OH, NO2, CN, halo, and substituted or unsubstituted alkyl, alkylcarbonyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, heteroaryl, amino, alkoxy, carboxy, carbalkoxy, carboxamido, sulfonyl, sulfonamido, sulfinyl, monoalkylaminosulfinyl, dialkylaminosulfinyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, alkylsulfonylamino, hydroxysulfonyloxy, alkoxysulfonyloxy, alkylsulfonyloxy, hydroxysulfonyl, alkoxysulfonyl, alkylsulfonylalkyl, monoalkylaminosulfonylalkyl, dialkylaminosulfonylalkyl, monoalkylaminosulfinylalkyl, and dialkylaminosulfinylalkyl;
X4 represents N or CR14;
X5 represents N;
R14 independently represents a substituent selected from the group consisting of H, OH, NO2, CN, halo, and substituted or unsubstituted alkyl, alkylcarbonyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, heteroaryl, amino, alkoxy, carboxy, carbalkoxy, carboxamido, sulfonyl, sulfonamido, sulfinyl, monoalkylaminosulfinyl, dialkylaminosulfinyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, alkylsulfonylamino, hydroxysulfonyloxy, alkoxysulfonyloxy, alkylsulfonyloxy, hydroxysulfonyl, alkoxysulfonyl, alkylsulfonylalkyl, monoalkylaminosulfonylalkyl, dialkylaminosulfonylalkyl, monoalkylaminosulfinylalkyl, and dialkylaminosulfinylalkyl; or the pharmaceutically acceptable salts of the compound.