US 11,884,664 B2
Protein tyrosine phosphatase inhibitors
James Francis Blake, Longmont, CO (US); Mark Laurence Boys, Lyons, CO (US); Mark Joseph Chicarelli, Longmont, CO (US); Adam Wade Cook, Broomfield, CO (US); Mohamed S. A. Elsayed, Boulder, CO (US); Jay Bradford Fell, Denver, CO (US); John P. Fischer, Longmont, CO (US); Ronald Jay Hinklin, Longmont, CO (US); Yutong Jiang, Longmont, CO (US); Oren Teague McNulty, Nederland, CO (US); Macedonio J. Mejia, Denver, CO (US); Martha E. Rodriguez, Lafayette, CO (US); and Christina Elizabeth Wong, Boulder, CO (US)
Assigned to Array BioPharma Inc., Boulder, CO (US)
Filed by Array BioPharma Inc., Boulder, CO (US)
Filed on Apr. 13, 2022, as Appl. No. 17/720,070.
Application 17/720,070 is a continuation of application No. 16/835,702, filed on Mar. 31, 2020, granted, now 11,634,417.
Claims priority of provisional application 62/992,558, filed on Mar. 20, 2020.
Claims priority of provisional application 62/828,356, filed on Apr. 2, 2019.
Prior Publication US 2022/0251083 A1, Aug. 11, 2022
Int. Cl. C07D 401/04 (2006.01); A61K 31/53 (2006.01); C07D 471/04 (2006.01); A61P 35/00 (2006.01); C07D 401/14 (2006.01); C07D 471/10 (2006.01); C07D 513/10 (2006.01); A61K 45/06 (2006.01)
CPC C07D 471/04 (2013.01) [A61P 35/00 (2018.01); C07D 401/14 (2013.01); C07D 471/10 (2013.01); C07D 513/10 (2013.01); A61K 45/06 (2013.01)] 16 Claims
 
1. A compound selected from Formula I:

OG Complex Work Unit Chemistry
or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein:
L1 is O;
R1 is selected from hydrogen and methyl;
R2 is selected from (a) phenyl, (b) a 5 to 6 membered heteroaryl wherein the heteroaryl contains one to four heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, wherein one nitrogen heteroatom may be substituted with oxygen to form an oxide, (c) an 8-10 membered bicyclic cycloalkyl, (d) a 10 membered bicyclic aryl, (e) a 9-10 membered bicyclic heterocycle wherein the heterocycle contains one to three heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and (f) a 9-10 membered bicyclic heteroaryl wherein the bicyclic heteroaryl contains one to three heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, wherein the phenyl, heteroaryl, bicyclic cycloalkyl, bicyclic aryl, bicyclic heterocycle and bicyclic heteroaryl are optionally substituted with one or more groups selected from the group consisting of halogen, cyano, oxo, C1-C3 alkyl optionally substituted with 1 to 3 groups selected from halogen, cyano and OH, C3-C6 cycloalkyl, C1-C3 alkoxy optionally substituted with 1 to 3 groups selected from halogen, cyano and OH, NHRa, and a 3 to 6 membered heterocycle optionally substituted with 1 to 3 groups selected from halogen, cyano and OH, wherein the heterocycle contains one or two heteroatoms selected from nitrogen, oxygen and sulfur;
R3 is selected from the group consisting of:

OG Complex Work Unit Chemistry
X10 is CR9 or O,
X11 is CH2 or O, wherein only one of X10 and X11 may be O;
R4 and R5 are independently selected from hydrogen and C1-C3 alkyl;
R6 is selected from the group consisting of hydrogen, OH and C1-C3 alkyl optionally substituted with an OH group, or
R6 and R9 together with the atoms to which they are attached form a 6 membered aryl or a 5 to 6 membered heteroaryl, wherein the heteroaryl contains 1 or 2 heteroatoms selected from nitrogen, oxygen and sulfur, wherein the aryl and heteroaryl are optionally substituted with 1 or 2 groups selected from the group consisting of halogen, cyano, C1-C3 alkyl and C1-C3 alkoxy;
R7 and R8 are hydrogen, or
R7 and R8 together with the atoms to which they are attached form an ethyl bridge such that R3 is an azabicyclic ring;
R99 is hydrogen or deuterium;
x is 1 or 2;
y is 0 or 1; and
Ra is hydrogen or C1-C4 alkyl optionally substituted with 1 to 3 groups selected from OH, methoxy, halogen and cyano.