US 9,809,541 B2
LSD1 inhibitors
Matthew Arnold Marx, San Diego, CA (US); Arkadii Vaisburg, Kirkland (CA); James Gail Christensen, San Diego, CA (US); and Robert Anthony Galemmo, Jr., San Francisco, CA (US)
Assigned to Mirati Therapeutics, Inc., San Diego, CA (US)
Filed by Mirati Therapeutics, Inc., San Diego, CA (US)
Filed on Nov. 3, 2016, as Appl. No. 15/343,008.
Claims priority of provisional application 62/272,082, filed on Dec. 29, 2015.
Claims priority of provisional application 62/295,369, filed on Feb. 15, 2016.
Prior Publication US 2017/0183308 A1, Jun. 29, 2017
Int. Cl. C07D 211/58 (2006.01); C07D 205/04 (2006.01); C07D 211/76 (2006.01); C07D 211/88 (2006.01); C07D 221/22 (2006.01); C07D 401/12 (2006.01); C07D 413/12 (2006.01); C07D 413/14 (2006.01); C07D 417/12 (2006.01); C07D 265/10 (2006.01); C07D 213/64 (2006.01)
CPC C07D 211/58 (2013.01) [C07D 205/04 (2013.01); C07D 211/76 (2013.01); C07D 211/88 (2013.01); C07D 213/64 (2013.01); C07D 221/22 (2013.01); C07D 265/10 (2013.01); C07D 401/12 (2013.01); C07D 413/12 (2013.01); C07D 413/14 (2013.01); C07D 417/12 (2013.01)] 62 Claims
 
1. A compound of formula (I) or formula (II):

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof:
wherein:
R1 is hydrogen, C1-C4 alkyl or C1-C4 acyl;
L is —(CH2)s—CR2R3—(CH2)n—;
R2 and R3 are each independently hydrogen, C1-C4 alkyl, —OR4 or aralkyl;
each R4 is independently hydrogen or C1-C4 alkyl;
X is —W—R5 or Y—R6;
W is —NR4— or —O—;
Y is —C(O)—, —S—, —SO—, —SO2—, —NR4SO2—, —SO2NR4— or —NR4C(O)—;
R5 is acyl, C1-C4 alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein each of said cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally independently substituted with one or more R8;
R6 is C1-C6 alkyl, aryl, —NR4R7 or heterocyclyl optionally independently substituted on one or more carbon atoms with C1-C6 alkyl, halogen, cyano, haloalkyl or optionally independently substituted on one or more nitrogen atom with —C(O)C1-C6alkyl;
—C(O)OC1-C6 alkyl; —C(O)NR4C1-C6alkyl, or —S(O)2NR4C1-C6 alkyl;
R7 is hydroxyl, alkoxy, —SO2C1-C6alkyl; —SO2cycloalkyl, or —SO2aryl, wherein the cycloalkyl or aryl of each of the —SO2cycloalkyl and —SO2aryl is optionally independently substituted with one or more R8;
each R8 is halogen, hydroxyl, amino, cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, haloalkyl, alkoxy, alkylamino, dialkylamino, cycloalkyl, aryl, heteroaryl, heterocyclyl, aralkyl, heteroarylalkyl, —(CH2)nCOOR4, —(CH2)nC(O)NR4OC1-C6alkyl;
—(CH2)nC(O)NR4SO2C1-C6alkyl, —(CH2)nC(O)NR4SO2cycloalkyl, —(CH2)nC(O)NR4SO2aryl, —C2-C6 alkenylC(O)OR4, —C2-C6 alkenylC(O)NR4SO2 C1-C4 alkyl, or —C2-C6 alkenylC(O) NR4SO2aryl, wherein each of the cycloalkyl, aryl, heteroaryl, heterocyclyl is optionally independently substituted with one or more C1-C3 alkyl or —CH2NR4SO2aryl;
m is 0 or 1;
s is 0 or 1;
each n is 0, 1, or 2;
each p is 0, 1 or 2;
each RA group is independently oxo or C1-C3 alkyl, or two RA groups on different ring atoms together form a C1-C3 bridge in which one of the bridge carbons is optionally replaced with —NH—; and
each Q1, Q2 and Q3 is independently hydrogen, halogen, haloalkyl, C1-C4-alkyl, or C1-C4-alkoxy.