US 11,753,418 B2
Compounds for the modulation of Myc activity
Jason J. Marineau, Franklin, MA (US); Peter B. Rahl, Natick, MA (US); Kevin Sprott, Needham, MA (US); Stephane Ciblat, Montreal (CA); Boubacar Sow, Saint-Laurent (CA); Robin Larouche-Gauthier, Montreal (CA); Lauren Berstler, Somerville, MA (US); Christopher Roberts, Belmont, MA (US); Yi Zhang, Belmont, MA (US); Francis Beaumier, Mont-Saint-Hilaire (CA); and Luce Lépissier, Montreal (CA)
Assigned to Syros Pharmaceuticals, Inc., Cambridge, MA (US)
Filed by Syros Pharmaceuticals, Inc., Cambridge, MA (US)
Filed on Aug. 25, 2021, as Appl. No. 17/411,965.
Application 17/411,965 is a continuation of application No. 15/579,830, granted, now 11,124,527, previously published as PCT/US2016/035690, filed on Jun. 3, 2016.
Claims priority of provisional application 62/171,766, filed on Jun. 5, 2015.
Prior Publication US 2022/0048927 A1, Feb. 17, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 513/04 (2006.01); A61P 35/00 (2006.01); C07D 495/04 (2006.01)
CPC C07D 513/04 (2013.01) [A61P 35/00 (2018.01); C07D 495/04 (2013.01)] 30 Claims
 
1. A compound of structural formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
each of X1, X2, X3 and X4 is independently selected from the group consisting of C(R), N and N(O), wherein one or two of X1, X2, X3 and X4 is N or one of X1, X2, X3 and X4 is N(O);
each R is independently selected from the group consisting of hydrogen, halogen, —CN, C1-C8 alkyl, C1-C8 heteroalkyl, N(R3a)(R3b), C(O)(C1-C6 alkyl), C(O)O(C1-C6 alkyl), (C0-C6 alkylene)-carbocyclyl, (C1-C6 heteroalkylene)-carbocyclyl, (C0-C6 alkylene)-heterocyclyl, (C1-C6 heteroalkylene)-heterocyclyl, (C0-C6 alkylene)-aryl, (C1-C6 heteroalkylene)-aryl, and (C0-C6 alkylene)-heteroaryl, wherein any alkyl, alkylene, heteroalkyl, heteroalkylene, carbocyclyl, heterocyclyl, aryl or heteroaryl portion of R is optionally and independently substituted;
Y is selected from the group consisting of O, S and N(R3a);
Z is selected from the group consisting of C(R4a)(N(R5)(R6)) and N(R1);
R1 is selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, (C0-C6 alkylene)-carbocyclyl, (C1-C6 heteroalkylene)-carbocyclyl, (C0-C6 alkylene)-heterocyclyl, (C1-C6 heteroalkylene)-heterocyclyl, (C0-C6 alkylene)-aryl, (C1-C6 heteroalkylene)-aryl, (C0-C6 alkylene)-heteroaryl, (C1-C6 heteroalkylene)-heteroaryl, CH2C(O)OR7, CH2C(O)N(R10)(R11), and CH2CH2N(R10)(R11) wherein:
R10 is selected from the group consisting of hydrogen and C1-C4 alkyl;
R11 is selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 heteroalkyl, (C0-C4 alkylene)-carbocyclyl, (C0-C4 alkylene)-heterocyclyl, (C0-C4 alkylene)-aryl, (C0-C4 alkylene)-heteroaryl, (C1-C4 alkyl)-O—(C1-C4 alkyl), (C1-C4 alkyl)-N—(C1-C4 alkyl)2, (C1-C4 alkyl)-NH—(C1-C4 alkyl), C(O)—(C1-C4 alkyl), and C(O)—O—(C1-C4 alkyl), or
R10 and R11 are taken together with the nitrogen atom to which they are commonly bound to form a 4-11 membered heterocyclyl or heteroaryl; and any alkyl, alkylene, heteroalkyl, heteroalkylene, heterocyclyl, heteroaryl, aryl or carbocyclyl portion of R1 is optionally substituted;
R2 is selected from the group consisting of C(R2a)(R2b)(R2c), carbocyclyl, aryl, heterocyclyl and heteroaryl, wherein any carbocyclyl, aryl, heterocyclyl and heteroaryl is optionally substituted;
R2a is selected from the group consisting of hydrogen, halogen, —CN, C1-C4 alkyl, C1-C4 heteroalkyl and C1-C4 haloalkyl, wherein any alkyl, heteroalkyl or haloalkyl is optionally substituted;
each of R2b and R2c is independently selected from the group consisting of hydrogen, halogen, —CN, C1-C6 alkyl, C1-C6 heteroalkyl, C(O)(C1-C6 alkyl), C(O)(C1-C6 heteroalkyl), C(O)O(C1-C6 alkyl), C(O)O(C1-C6 heteroalkyl), C(O)N(R3a)(R3b), (C0-C6 alkylene)-carbocyclyl, (C1-C6 heteroalkylene)-carbocyclyl, (C0-C6 alkylene)-heterocyclyl, (C1-C6 heteroalkylene)-heterocyclyl, (C0-C6 alkylene)-aryl, (C1-C6 heteroalkylene)-aryl, (C0-C6 alkylene)-heteroaryl and (C1-C6 heteroalkylene)-heteroaryl, wherein any alkyl, alkylene, heteroalkyl, heteroalkylene, carbocyclyl, heterocyclyl, aryl or heteroaryl portion of R2b and R2c is optionally and independently substituted;
each of R3a and R3b is independently selected from the group consisting of hydrogen, C1-C6 alkyl, or C1-C6 heteroalkyl, each of which is optionally substituted;
each R4 is independently selected from the group consisting of halogen, —CN, C1-C8 alkyl, C1-C8 heteroalkyl, N(R3a)(R3b), C(O)(C1-C6 alkyl), C(O)(C1-C6 heteroalkyl), C(O)O(C1-C6 alkyl), C(O)N(R3a)(R3b), (C0-C6 alkylene)-carbocyclyl, (C1-C6 heteroalkylene)-carbocyclyl, (C0-C6 alkylene)-heterocyclyl, (C1-C6 heteroalkylene)-heterocyclyl, (C0-C6 alkylene)-aryl, (C1-C6 heteroalkylene)-aryl, (C0-C6 alkylene)-heteroaryl, and (C1-C6 heteroalkylene)-heteroaryl, wherein any alkyl, alkylene, heteroalkyl, heteroalkylene, carbocyclyl, heterocyclyl, aryl or heteroaryl portion of R4 is optionally and independently substituted;
R4a is selected from the group consisting of hydrogen and C1-C6 alkyl;
each of R5 and R6 is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C(O)(C1-C6 alkyl), C(O)O(C1-C6 alkyl), (C0-C6 alkylene)-carbocyclyl, (C1-C6 heteroalkylene)-carbocyclyl, (C0-C6 alkylene)-heterocyclyl, (C1-C6 heteroalkylene)-heterocyclyl, (C0-C6 alkylene)-aryl, (C1-C6 heteroalkylene)-aryl, (C0-C6 alkylene)-heteroaryl, and (C1-C6 heteroalkylene)-heteroaryl, wherein any alkyl, alkylene, heteroalkyl, heteroalkylene, carbocyclyl, heterocyclyl, aryl or heteroaryl portion of each of R5 and R6 is optionally and independently substituted; or
R5 and R6 are taken together with the nitrogen atom to which they are commonly bound to form an optionally substituted heterocyclyl;
R7 is selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, (C0-C3 alkylene)-carbocyclyl, and (C0-C3 alkylene)-heterocyclyl;
R12 is selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, (C0-C3 alkylene)-carbocyclyl, and (C0-C3 alkylene)-heterocyclyl;
n is 0, 1 or 2;
m is 0, 1 or 2;
n+m=1, 2 or 3; and
p is 0, 1, 2, 3, 4, 5 or 6.