US 10,889,593 B2
Compounds targeting proteins, compositions, methods, and uses thereof
Kyle W. H. Chan, San Diego, CA (US); Paul E. Erdman, San Diego, CA (US); Leah Fung, San Diego, CA (US); Frank Mercurio, Rancho Santa Fe, CA (US); Robert Sullivan, Vista, CA (US); and Eduardo Torres, San Diego, CA (US)
Assigned to BioTheryX, Inc., Chappaqua, NY (US)
Filed by BioTheryX, Inc., Chappaqua, NY (US)
Filed on Jun. 28, 2019, as Appl. No. 16/457,409.
Application 16/457,409 is a continuation of application No. 16/011,090, filed on Jun. 18, 2018, granted, now 10,336,771.
Application 16/011,090 is a continuation of application No. 15/847,628, filed on Dec. 19, 2017, granted, now 10,040,804, issued on Aug. 7, 2018.
Claims priority of provisional application 62/437,400, filed on Dec. 21, 2016.
Claims priority of provisional application 62/485,563, filed on Apr. 14, 2017.
Claims priority of provisional application 62/538,203, filed on Jul. 28, 2017.
Prior Publication US 2019/0322683 A1, Oct. 24, 2019
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 495/04 (2006.01); C07D 519/00 (2006.01); A61P 29/00 (2006.01); A61P 19/02 (2006.01); A61P 35/00 (2006.01); A61P 1/00 (2006.01); A61P 11/00 (2006.01); A61P 25/28 (2006.01); A61P 17/06 (2006.01)
CPC C07D 495/04 (2013.01) [A61P 1/00 (2018.01); A61P 11/00 (2018.01); A61P 17/06 (2018.01); A61P 19/02 (2018.01); A61P 25/28 (2018.01); A61P 29/00 (2018.01); A61P 35/00 (2018.01); C07D 519/00 (2013.01)] 27 Claims
 
1. A method of treating cancer associated with a cytokine, aiolos, ikaros, helios, CKla, or GSPT1, comprising administering a compound of Formula (IIa) or a pharmaceutically acceptable salt thereof to a subject in need thereof,

OG Complex Work Unit Drawing
wherein:
R1 and R2 are each independently H, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C6-C10 aryl, optionally substituted 3 to 10-membered heterocyclyl, or optionally substituted 5 to 10-membered heteroaryl; or
one of R1 and R2 is H, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C6-C10 aryl, optionally substituted 3 to 10-membered

OG Complex Work Unit Drawing
heterocyclyl, optionally substituted 5 to 10-membered heteroaryl, or L-Y; and
the other of R1 and R2 is optionally substituted C3-C8 cycloalkyl, optionally substituted C6-C10 aryl, optionally substituted 3 to 10-membered heterocyclyl, optionally substituted 5 to 10-membered heteroaryl, or L-Y;

OG Complex Work Unit Drawing

OG Complex Work Unit Drawing
provided that when one of R1 and R2 is then the other R1 and R2 is not L-Y;
R5 is H, deuterium, or optionally substituted C1-C6 alkyl;
n is 2 or 3;
each of Qa and Qb is independently C═O, C=S, or CH2;
X is CH2 or C(═O);
X1 is H, deuterium, halogen, or optionally substituted C1-C6 alkyl;
m is 1, 2, 3, 4, or 5;
X2 is (CH2)a, C═O, NH, or N—(optionally substituted C1-C6 alkyl);
X3 is 0, NI-2 or S;
a is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
R8 is optionally substituted C3-C10 cycloalkyl, optionally substituted C6-C10 aryl, optionally substituted 5 to 10-membered heteroaryl, optionally substituted 3 to 10-membered heterocyclyl, optionally substituted C3-C10 cycloalkyl(C1-C6 alkyl), optionally substituted C6-C10 aryl(C1-C6 alkyl), optionally substituted 5 to 10 membered heteroaryl(C1-C6 alkyl), or optionally substituted 3 to 10 membered heterocyclyl(C1-C6 alkyl);

OG Complex Work Unit Drawing
L is each Z1 and Z2 arc each is —CH2-;
each R6 is absent or independently absent or C1-C6 alkyl; and
each Y is independently selected from a group consisting of

OG Complex Work Unit Drawing

OG Complex Work Unit Drawing
wherein * represents the point of attachment to L.