	US 11,859,021 B2
	Compounds for regulating trained immunity, and their methods of use
Henricus Marie Janssen, Eindhoven (NL); Freek Johannes Maria Hoeben, Liessel (NL); Bas Van Genabeek, Sint-Michielsgestel (NL); Serge Hendrikus Mathijs Sontjens, Eindhoven (NL); and Willem J. M. Mulder, New York, NY (US)
Assigned to Icahn School of Medicine at Mount Sinai, New York, NY (US); and Trained Therapeutix Discovery, Inc., Dallas, TX (US)
Filed by Trained Therapeutix Discovery, Inc., Dallas, TX (US); and Icahn School of Medicine at Mount Sinai, New York, NY (US)
Filed on Mar. 18, 2022, as Appl. No. 17/698,971.
Claims priority of provisional application 63/163,428, filed on Mar. 19, 2021.
Prior Publication US 2022/0332762 A1, Oct. 20, 2022
Int. Cl. C07K 9/00 (2006.01); A61K 9/51 (2006.01); C07K 16/28 (2006.01); B82Y 5/00 (2011.01)

CPC C07K 9/001 (2013.01) [A61K 9/5123 (2013.01); A61K 9/5169 (2013.01); A61K 9/5192 (2013.01); C07K 16/2818 (2013.01); B82Y 5/00 (2013.01)]

40 Claims

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof,

wherein:

R¹is —H or —C(O)—R^X;

R²and R³are each independently selected from the group consisting of —H, alkyl, aryl, alkylene-aryl, —C(O)-alkyl, and —C(O)-aryl;

R⁴, R⁵, and R^5′ are each alkyl;

R⁶and R¹¹are each independently —H or alkyl;

R⁷is —Y-triazolyl-L;

Y is alkylene;

L is selected from the group consisting of a fatty acid chain, -alkylene-C(O)—W, -alkylene-O—C(O)—W, -alkylene-N-(alkylene-C(O)—NR¹¹-alkylene-NR¹¹—C(O)—W)₂, and -alkylene-N-(alkylene-C(O)—W)₂;

W is a fatty acid chain, —O-alkylene-C(H)(OR⁸)-alkylene-OR⁹, a phospholipid, or a sterol;

R⁸and R⁹are each independently R^Xor —C(O)—R^X;

R²², R³³, R^33′, R⁴⁴, R^44′, R⁵⁵, and R^55′ are each independently H or R^A;

R^Xis a fatty acid chain;

wherein each aforementioned alkyl, alkylene, alkylene-aryl, aryl, and triazolyl is optionally substituted with one or more R^A, wherein R^Ais independently selected for each occurrence from the group consisting of hydrogen, halo, alkoxy, haloalkoxy, cyano, hydroxyl, —N(R^C)(R^D), —C(O)N(R^C)(R^D), —N(R^C)C(O)R^B, —OC(O)NR^CR^D, —NR^CC(O)OR^B, —OC(O)R^B, —C(O)OR^B, —C(O)R^B, —CO₂H, —NO₂, —SH, S(O)_XR^B, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, and R^B; wherein X is 0, 1, or 2,

R^Cand R^Dare independently selected for each occurrence from the group consisting of hydrogen, alkyl, haloalkyl —C(O)R^B, and —C(O)OR^B; or R^Cand R^Dare taken together with the nitrogen to which they are attached to form a heterocyclic ring optionally substituted with R^A; and

R^Bis alkyl, alkenyl, or alkynyl optionally substituted with one or more fluoro.