	US 12,187,721 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, Longmont, CO (US); John Peter Fischer, Longmont, CO (US); Ronald Jay Hinklin, 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)
Appl. No. 17/285,997
Filed by Array BioPharma Inc., Boulder, CO (US)
PCT Filed Oct. 17, 2019, PCT No. PCT/US2019/056786 § 371(c)(1), (2) Date Apr. 16, 2021, PCT Pub. No. WO2020/081848, PCT Pub. Date Apr. 23, 2020.
Claims priority of provisional application 62/916,119, filed on Oct. 16, 2019.
Claims priority of provisional application 62/746,952, filed on Oct. 17, 2018.
Prior Publication US 2021/0380582 A1, Dec. 9, 2021
Int. Cl. C07D 471/04 (2006.01); C07D 519/00 (2006.01)

CPC C07D 471/04 (2013.01) [C07D 519/00 (2013.01)]

22 Claims

1. A compound selected from Formula Ia:

or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein:

X₁is selected from CH and N;

X₂is selected from CH and N;

X₃is selected from CH and N;

L₁is S;

R¹is selected from phenyl, heteroaryl, bicyclic aryl, bicyclic heterocyclyl, and bicyclic heteroaryl,

wherein the phenyl, heteroaryl, bicyclic aryl, bicyclic heterocyclyl and bicyclic heteroaryl are optionally substituted with one or more groups selected from the group consisting of halogen, OH, oxo, cyano, alkyl optionally substituted with halogen, cyano or OH, —O(alkyl) optionally substituted with halogen, cyano or OH, NHR^a, and a heterocycle optionally substituted with halogen, cyano, OH or alkyl optionally substituted with OH or oxo;

R²is:

X₁₁is selected from CR¹³R¹⁴, SiR¹³R¹⁴, NH and O;

X₁₂is selected from CHR¹⁵and NH, wherein one or both of X₁₁and X₁₂must be carbon;

R¹⁰is selected from hydrogen and alkyl;

R¹¹is selected from hydrogen, OH and CH₂NH₂;

R¹², R¹⁶and R¹⁷are hydrogen;

R¹³is selected from hydrogen, OH, and (C₀-C₃alkyl)NR^bR^c;

R¹⁴is selected from hydrogen, OH, alkyl optionally substituted with halogen, OH, methyl, OCH₃and a heteroaryl;

R¹⁵is selected from hydrogen or NH₂;

or one of the following groups may join together:

R¹⁰and R¹¹may join together as CH₂NHCH₂to form a fused bicyclic,

R¹⁰and R¹⁵may join together as alkyl to form a bridged bicyclic,

R¹¹and R¹²may join together as alkyl substituted with NH₂to form a spirocycle,

R¹³and R¹⁴may join together as a group selected from cycloalkyl, heterocycle, bicyclic carbocycle, and bicyclic heterocycle, wherein the cycloalkyl, heterocycle, carbocycle and heterocycle are optionally substituted with F, Cl, OH, OCH₃, CN, methyl or NH₂to form a spirocycle,

R¹⁰and R¹⁶may join together as alkyl, O or NH to form a bridged bicyclic,

R¹¹and R¹⁵may join together as alkyl to form a bridged bicyclic,

R¹¹and R¹⁶may join together as alkyl or O to form a bridged bicyclic,

R¹¹and R¹⁷may join together as alkyl to form a bridged bicyclic, or

R¹³and R¹⁵may join together as NHCH₂, or cycloalkyl wherein the cycloalkyl is substituted with NH₂to form a fused bicyclic;

R⁴⁸is selected from hydrogen and methyl;

R^ais hydrogen, alkyl optionally substituted with OH, methoxy, halogen or cyano, or cyclopropyl;

R^band R^care independently selected from hydrogen, alkyl and a Boc group; and

a, b, c and d are selected from 0 and 1.