	US 12,234,220 B2
	Immunomodulatory compounds
Nathanael Gray, Boston, MA (US); Tinghu Zhang, Brookline, MA (US); Eric Fischer, Chestnut Hill, MA (US); Alyssa Verano, Allston, MA (US); Zhixiang He, Brookline, MA (US); Guangyan Du, Jamaica Plain, MA (US); Katherine Donovan, Boston, MA (US); Radoslaw Nowak, Boston, MA (US); Jing Ting Christine Yuan, Brookline, MA (US); and Hu Liu, Newton, MA (US)
Assigned to DANA-FARBER CANCER INSTITUTE, INC., Boston, MA (US)
Appl. No. 17/255,738
Filed by DANA-FARBER CANCER INSTITUTE, INC., Boston, MA (US)
PCT Filed Jun. 27, 2019, PCT No. PCT/US2019/039509 § 371(c)(1), (2) Date Dec. 23, 2020, PCT Pub. No. WO2020/006233, PCT Pub. Date Jan. 2, 2020.
Claims priority of provisional application 62/692,176, filed on Jun. 29, 2018.
Prior Publication US 2021/0284624 A1, Sep. 16, 2021
Int. Cl. C07D 401/12 (2006.01)

CPC C07D 401/12 (2013.01)

42 Claims

1. A compound having a structure represented by formula (I):

wherein A represents:

wherein X is C and X₁is N, or

X and X₁are both C, or

X and X₁are both N;

wherein R₁is absent if X₁represents N, and if X₁represents C, R₁represents H, or together with R₂and the other atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group or an optionally substituted 6-membered heterocyclic group;

R₂represents H, halo, hydroxy, optionally substituted C1-C4 alkoxy, 1-benzyl-4-piperidinoxy, optionally substituted 5- or 6-membered carbocyclic group, optionally substituted 5- or 6-membered heterocyclic group, optionally substituted aryl, optionally substituted heteroaryl, or NR₆R₇, wherein each of R₆and R₇independently represents H or a substituent or R₂together with R₁and the other atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group or an optionally substituted 6-membered heterocyclic group;

if X represents N, R₃is absent, and if X represents C, R₃independently represents H, halo, hydroxy, optionally substituted amine, 1-benzyl-4-piperidinoxy, optionally substituted 5- or 6-membered carbocyclic group, optionally substituted 5- or 6-membered heterocyclic group, optionally substituted aryl, optionally substituted heteroaryl, or NR₆R₇, or wherein R₂and R₃, or R₃and R₄, together with the atoms to which they are bound form an optionally substituted 6-membered heterocyclic group;

R₄, and R₅each independently represents H, halo, hydroxy, optionally substituted amine, 1-benzyl-4-piperidinoxy, optionally substituted 5- or 6-membered carbocyclic group, optionally substituted 6-membered heterocyclic group, optionally substituted aryl, or NR₆R₇, or wherein R₄and R₅, together with the atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group or an optionally substituted 6-membered heterocyclic group;

wherein R₈represents H, optionally substituted C1-C4 alkyl, optionally substituted amine, optionally substituted C1-C4 alkoxy, optionally substituted aryl, or an optionally substituted heteroaryl group, and R₉represents H, halo, hydroxy, optionally substituted C1-C4 alkyl, optionally substituted amine, optionally substituted C1-C4 alkoxy, optionally substituted 5- or 6-membered carbocyclic group, or an optionally substituted 5- or 6-membered heterocyclic group;

wherein R₁₀represents H, optionally substituted C1-C4 alkyl, optionally substituted amine, optionally substituted C1-C4 alkoxy, optionally substituted aryl, or an optionally substituted heteroaryl group, and R₁₁, R₁₂, R₁₃, R₁₄, and R₁₅each independently represents H, halo, hydroxy, optionally substituted C1-C4 alkoxy, optionally substituted aryl, optionally substituted heteroaryl, or NR₆R₇, wherein each of R₆and R₇independently represents H or a substituent, or R₁₁together with R₁₂and the other atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group or an optionally substituted 5- or 6-membered heterocyclic group, or R₁₂together with R₁₃and the other atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group or an optionally substituted 5- or 6-membered heterocyclic group, or R₁₃together with R₁₄and the other atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group or an optionally substituted 5- or 6-membered heterocyclic group, or R₁₄together with R₁₅and the other atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group or an optionally substituted 5- or 6-membered heterocyclic group;

wherein R₁₆, R₁₇, R₁₈and R₁₉independently represent H or a substituent, or wherein R₁₆and R₁₇together with the atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group, or wherein R₁₆and R₁₇together with the atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group, an optionally substituted 5- or 6-membered heterocyclic group, or wherein R₁₈and R₁₉together with the atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group, or an optionally substituted 5- or 6-membered heterocyclic group; or

wherein R₂₀, R₂₁, R₂₂and R₂₃independently represent H or a substituent, or wherein R₂₀and R₂₁together with the atoms to which they are bound form an optionally substituted 5- or 6-membered heterocyclic group, or wherein R₂₁and R₂₂together with the atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group, an optionally substituted 5- or 6-membered heterocyclic group, or wherein R₂₂and R₂₃together with the atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group, or an optionally substituted 5- or 6-membered heterocyclic group;

wherein each optional substituent is independently alkyl, alkoxy, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, heteroaryl, aralkyl, halo, hydroxyl, aryloxy, alkylthio, arylthio, cyano, carbonyl, carboxyl, amino, amido, sulfonyl, or an amino acid,

or a pharmaceutically acceptable salt or stereoisomer thereof.