	US 12,220,399 B2
	Pharmaceutical compositions comprising one or more pyrone compounds, and their use for treating inflammatory and neurodegenerative diseases
Armen Manoukian, North York (CA); Fabrizio Mastronardi, Maple (CA); Sam Scanga, Burlington (CA); Frank Mercurio, Rancho Santa Fe, CA (US); and Kyle W. H. Chan, San Diego, CA (US)
Assigned to Adiptotec, Inc., San Diego, CA (US)
Filed by NeuroTheryX Canada LTD, Toronto (CA)
Filed on Sep. 1, 2022, as Appl. No. 17/929,285.
Application 17/929,285 is a division of application No. 15/288,780, filed on Oct. 7, 2016, granted, now 11,433,047, issued on Sep. 6, 2022.
Claims priority of provisional application 62/239,783, filed on Oct. 9, 2015.
Prior Publication US 2023/0136999 A1, May 4, 2023
Int. Cl. A61K 31/366 (2006.01); A61K 31/382 (2006.01); A61K 31/4433 (2006.01)

CPC A61K 31/366 (2013.01) [A61K 31/382 (2013.01); A61K 31/4433 (2013.01)]

17 Claims

1. A method for treating, preventing, or ameliorating one or more symptoms of an inflammatory, neurodegenerative, or immune-mediated disease in a subject, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a compound of Formula I:

or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof, or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; and a pharmaceutically acceptable excipient; wherein:

R³is hydrogen or deuterium; and R⁵is (a) hydrogen, deuterium, cyano, halo, or nitro; or (b) C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-7cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl; or

R³is (a) hydrogen, deuterium, cyano, halo, or nitro; or (b) C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-7cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl; and R⁵is hydrogen or deuterium;

R⁴is (a) hydrogen, deuterium, cyano, halo, or nitro; (b) C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-7cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl; or (c) -C(O)R^1a,-C(O)OR^1a,-C(O)NR^1bR^1c,-C(O)SR^1a,-C(NR^1a) NR^1bR^1c,-C(S)R^1a,-C(S)OR^1a, —C(S)NR^1bR^1c,-OR^1a,-OC(O)R^1a,-OC(O)OR^1a,-OC(O)NR^1bR^1c,-OC(O)SR^1a, —OC(═NR^1a)NR^1bR^1c,-OC(S)R^1a,-OC(S)OR^1a,-OC(S)NR^1bR^1c,-OS(O)R^1a,-OS(O)₂R^1a, -OS(O)NR^1bR^1c,-OS(O)₂NR^1bR^1c,-NR^1bR^1c,-NR^1aC(O)R^1d,-NR^1aC(O)OR^1d, -NR^1aC(O)NR^1bR^1c,-NR^1aC(O)SR^1d,-NR^1aC(═NR^1d) NR^1bR^1c,-NR^1aC(S)R^1d,-NR^1aC(S)OR^1d, —NR^eC(O)NR^fRg,-NR^eC(O)SR^f,-NR^eC(═NR^h)NR^fR^g,-NR^eC(S)R^h,-NR^eC(S)OR^f, —NR^eC(S)NR^fR^g,-NR^eS(O)R^h,-NR^eS(O)₂R^h,-NR^eS(O)NR^fR^g,-NR^eS(O)₂NR^fR^g,-SR^e, —S(O)R^e,-S(O)₂R^e,-S(O)NR^fR^g, and -S(O)₂NR^fR^g; wherein each R^e, R^f, R^g, and R^his independently (i) hydrogen or deuterium; (ii) C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-7cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl; or (iii) R^fand R^gtogether with the N atom to which they are attached form heterocyclyl.