US 12,133,853 B2
Pyruvate kinase activators for use in treating blood disorders
Giovanni Cianchetta, Boxford, MA (US); Tao Liu, Wellesley, MA (US); Anil Kumar Padyana, Lexington, MA (US); Zhihua Sui, Audubon, PA (US); Zhenwei Cai, Princeton, NJ (US); Dawei Cui, Shanghai (CN); and Jingjing Ji, Shanghai (CN)
Assigned to Agios Pharmaceuticals, Inc., Cambridge, MA (US)
Filed by Agios Pharmaceuticals, Inc., Cambridge, MA (US)
Filed on Jan. 20, 2023, as Appl. No. 18/099,311.
Application 18/099,311 is a continuation of application No. 16/639,081, granted, now 11,590,132, previously published as PCT/US2018/000128, filed on Aug. 15, 2018.
Claims priority of provisional application 62/673,526, filed on May 18, 2018.
Claims priority of provisional application 62/673,533, filed on May 18, 2018.
Prior Publication US 2023/0226055 A1, Jul. 20, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 241/36 (2006.01); A61K 31/5025 (2006.01); A61K 31/506 (2006.01); A61K 31/519 (2006.01); A61P 7/06 (2006.01); A61P 7/08 (2006.01); A61P 31/10 (2006.01); C07D 513/04 (2006.01); C07D 513/14 (2006.01); A61K 45/06 (2006.01)
CPC A61K 31/5025 (2013.01) [A61K 31/506 (2013.01); A61K 31/519 (2013.01); C07D 241/36 (2013.01); C07D 513/14 (2013.01); A61K 45/06 (2013.01)] 25 Claims
 
1. A compound represented by the following structural formula:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
R1 is hydrogen, an optionally substituted alkyl, an optionally substituted haloalkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted heterocyclyl, an optionally substituted aryl, —ORo1, —C(═O)Rc1, or a nitrogen protecting group; wherein:
Ro1 is hydrogen, optionally substituted alkyl, or an oxygen protecting group;
Rc1 is optionally substituted alkyl or —N(Rcn)2, wherein each instance of Rcn is independently hydrogen, —C1-6 alkyl, or a nitrogen protecting group;
R2 is an optionally substituted 5- or 6-membered monocyclic heteroaryl;
Q is an optionally substituted 5-membered monocyclic heteroaryl;
Ra and Rb are each independently hydrogen, a halogen, —CN, —NO2, —N3, an optionally substituted alkyl, —ORo3, —N(Rn1)2, —C(═O)N(Rn1)2, or —C(═O)Rc2; or alternatively Ra and Rb can be taken together with the carbon atom to which they are attached to form an optionally substituted cycloalkyl or an optionally substituted heterocyclyl; wherein:
each instance of Rn1 is independently hydrogen, an optionally substituted —C1-C6 alkyl, or a nitrogen protecting group;
Ro3 is hydrogen, an optionally substituted —C1-C6 alkyl, or an oxygen protecting group; and
Rc2 is an optionally substituted —C1-C6 alkyl; and
Rj and Rk are each independently hydrogen, a halogen, —CN, —ORo7, —N(Rn5)2, —N(Rn5)C(═O) Rc5, —C(═O)N(Rn5)2, —C(═O)Rc5, —C(═O)ORo7, —SRjs, —S(═O)2Rjs,
—S(═O)Rjs, or an optionally substituted —C1-C6 alkyl; or alternatively Rj and Rk can be taken together with the carbon atom to which they are attached to form C═O, an optionally substituted C1-C6 monocyclic cycloalkyl ring, or an optionally substituted C3-C6 monocyclic heterocyclyl ring; wherein:
each instance of Rn5 is independently hydrogen, an optionally substituted —C1-C6 alkyl, —ORo8, or a nitrogen protecting group, wherein Ro8 is hydrogen, an optionally substituted —C1-C6 alkyl, or an oxygen protecting group;
each instance of Ro7 is independently hydrogen, an optionally substituted —C1-C6 alkyl, or an oxygen protecting group;
each instance of Rc5 is independently an optionally substituted —C1-C6 alkyl; and
each instance of Rjs is independently an optionally substituted
—C1-C6 alkyl, an optionally substituted C6-12 aryl, an optionally substituted heteroaryl, or a sulfur protecting group.