US 11,654,147 B2
ALK2 inhibitors and methods for inhibiting BMP signaling
Paul B. Yu, Boston, MA (US); Wenwei Huang, Rockville, MD (US); Philip Edward Sanderson, Bethesda, MD (US); Jian-Kang Jiang, Columbia, MD (US); Khalida Shamim, Gaithersburg, MD (US); Wei Zheng, Potomac, MD (US); Xiuli Huang, Potomac, MD (US); Gregory Tawa, Doylestown, PA (US); Arthur Lee, San Jose, CA (US); Asaf Alimardanov, North Bethesda, MD (US); and Junfeng Huang, Woodstock, MD (US)
Assigned to The Brigham and Women's Hospital, Inc., Boston, MA (US); and The United States of America, as Represented by the Secretary, Dept. of Health and Human Services, Bethesda, MD (US)
Filed by The Brigham and Women's Hospital, Inc., Boston, MA (US); and The United States of America, as Represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US)
Filed on Jun. 7, 2021, as Appl. No. 17/340,589.
Application 17/340,589 is a continuation of application No. 16/608,489, granted, now 11,026,947, previously published as PCT/US2018/029626, filed on Apr. 26, 2018.
Claims priority of provisional application 62/490,772, filed on Apr. 27, 2017.
Prior Publication US 2023/0000869 A1, Jan. 5, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/519 (2006.01); A61P 19/08 (2006.01); A61K 31/5377 (2006.01); A61K 31/551 (2006.01); A61K 31/675 (2006.01); A61K 45/06 (2006.01); C07D 487/04 (2006.01); C07D 519/00 (2006.01); C07F 9/6561 (2006.01)
CPC A61K 31/519 (2013.01) [A61K 31/5377 (2013.01); A61K 31/551 (2013.01); A61K 31/675 (2013.01); A61K 45/06 (2013.01); A61P 19/08 (2018.01); C07D 487/04 (2013.01); C07D 519/00 (2013.01); C07F 9/6561 (2013.01)] 13 Claims
 
1. A compound of formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
A1 is NR4a or CR4bR5;
B1 is N or CR2;
Z1 is N or CR3;
R1 is selected from cycloalkyl, aryl, heteroaryl, and heterocyclyl;
R2 is H, CN, NO2, alkyl, or amino;
R3 is selected from H, CN, NO2, alkyl, alkoxy, heterocyclyloxy, heteroaryloxy, aryloxy, cycloalkyloxy, carbonyl, amino, amido, sulfonyl, sulfonamido, cycloalkyl, aryl, heterocyclyl, and heteroaryl;
R4a is selected from alkyl, alkenyl, alkynyl, carbonyl, O, alkoxycarbonyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl;
R4b is selected from halo, CN, NO2, hydroxy, alkyl, alkenyl, alkynyl, alkoxy, heterocyclyloxy, heteroaryloxy, aryloxy, cycloalkyloxy, amino, amido, carbonyl, alkoxycarbonyl, carboxy, sulfonyl, sulfonamido, thio, cycloalkyl, aryl, heterocyclyl, and heteroaryl;
R5 is selected from H, halo, hydroxy and alkyl, or R4b and R5 together with A1 form a ring selected from cycloalkyl and heterocyclyl;
each R6 is independently selected from H, halo, CN, NO2, hydroxy, alkyl, alkenyl, alkynyl, alkoxy, heterocyclyloxy, heteroaryloxy, aryloxy, cycloalkyloxy, amino, amido, carbonyl, alkoxycarbonyl, carboxy, sulfonyl, sulfonamido, thio, cycloalkyl, aryl, heterocyclyl, and heteroaryl and oxo;
n is 0 or 1;
m is 0 or 1; and
x is 0, 1, 2, 3, or 4.