US 12,275,717 B2
6-heteroaryloxy benzimidazoles and azabenzimidazoles as JAK2 inhibitors
Craig E. Masse, Cambridge, MA (US); Jeremy R. Greenwood, Brooklyn, NY (US); Sayan Mondal, New York, NY (US); Jiayi Xu, Marlboro, NJ (US); Phani Ghanakota, Edison, NJ (US); Fiona Michelle McRobb, Brooklyn, NY (US); and Nicholas Boyles, Hillsboro, OR (US)
Assigned to Ajax Therapeutics, Inc., New York, NY (US)
Filed by Ajax Therapeutics, Inc., New York, NY (US)
Filed on Apr. 26, 2023, as Appl. No. 18/307,490.
Application 18/307,490 is a continuation of application No. 17/308,740, filed on May 5, 2021, granted, now 11,691,963.
Claims priority of provisional application 63/130,254, filed on Dec. 23, 2020.
Claims priority of provisional application 63/087,717, filed on Oct. 5, 2020.
Claims priority of provisional application 63/020,645, filed on May 6, 2020.
Prior Publication US 2023/0265075 A1, Aug. 24, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 401/14 (2006.01); C07D 401/12 (2006.01); C07D 405/14 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01); C07D 471/04 (2006.01)
CPC C07D 401/14 (2013.01) [C07D 401/12 (2013.01); C07D 405/14 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07D 471/04 (2013.01)] 29 Claims
 
1. A method of treating a hematological malignancy, comprising administering to a subject in need thereof a compound of Formula I-1:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
W is CRw or N;
X is CRx or N;
Y is CRy or N;
Z is —O— or —NRz—;
R″, Rx, and Ry are each independently hydrogen, halogen, —OR3, —N(R3) 2, —SR3, optionally substituted C1-6 aliphatic, or —CN;
Rz is hydrogen or optionally substituted C1-6 aliphatic;
R1 is —N(R)2, —N(R) C(O) R′, —C(O) N(R)2, or —N(R) C(O) N(R)2;
R2 is optionally substituted C1-6 aliphatic;
R3 is hydrogen or optionally substituted C1-6 aliphatic;
Ring A is optionally substituted 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, optionally substituted 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, optionally substituted 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclyl, optionally substituted 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or optionally substituted 7- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
L is a covalent bond or a bivalent C1-3 straight or branched hydrocarbon chain;
Ra is hydrogen, halogen, optionally substituted C1-6 aliphatic, optionally substituted phenyl, optionally substituted 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, optionally substituted 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclyl, optionally substituted 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or optionally substituted 7- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
each R is independently hydrogen, optionally substituted C1-6 aliphatic, optionally substituted 3- to 7-membered saturated or partially unsaturated carbocyclyl, or optionally substituted 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or two R when attached to the same nitrogen atom are taken together form an optionally substituted 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen, and sulfur; and
each R′ is independently optionally substituted C1-6 aliphatic or optionally substituted 3- to 7-membered saturated or partially unsaturated carbocyclyl.