	US 11,718,595 B2
	Non-ATP/catalytic site p38 Mitogen Activated Protein Kinase inhibitors
Paul S. Shapiro, Baltimore, MD (US); Alexander D. Mackerell, Jr., Baltimore, MD (US); Jeffrey D. Hasday, Timonium, MD (US); and Steven Fletcher, Baltimore, MD (US)
Assigned to University of Maryland, Baltimore, Baltimore, MD (US)
Filed by University of Maryland, Baltimore, Baltimore, MD (US)
Filed on Jun. 16, 2021, as Appl. No. 17/349,468.
Application 17/349,468 is a continuation of application No. 16/872,114, filed on May 11, 2020, granted, now 11,078,171.
Application 16/872,114 is a continuation of application No. PCT/US2019/064960, filed on Dec. 6, 2019.
Claims priority of provisional application 62/776,837, filed on Dec. 7, 2018.
Prior Publication US 2021/0317097 A1, Oct. 14, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 295/03 (2006.01)

CPC C07D 295/03 (2013.01)

19 Claims

1. A compound of Formula 1:

or a pharmaceutically acceptable salt thereof, wherein in Formula 1,

L¹is selected from —CH₂—, —C(CH₃)₂—, and —C(CH₂CH₂)—;

L²is selected from —NH—SO₂—, —NHCH₂—, —CH₂NH—, —NHCO—, —CONH, and —SO₂NH—;

each of R³, R⁴, R⁵, and R⁶is hydrogen; and

Ar¹is selected from:

wherein,

one of R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹²and R¹³is selected from hydrogen and —NR^1aR^2a, and each of the other of R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹²and R¹³is hydrogen; and

each of R^1aand R^2ais independently selected from hydrogen, C_1-10alkyl, and C_1-10alkyl substituted by one or more of substituents which are independently hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, —OR^a, —SR^a, —S(O)_tR^a(where t is 1 or 2), —OC(O)—R^a, —N(R^a)₂, —C(O)R^a, —C(O)OR^a, —OC(O)N(R^a)₂, —C(O)N(R^a)₂, —N(R^a)C(O)OR^a, —N(R^a)C(O)R^a, —N(R^a)C(O)N(R^a)₂, —N(R^a)C(NR^a)N(R^a)₂, —N(R^a)S(O)_tR^a(where t is 1 or 2), —S(O)_tR^a(where t is 1 or 2), —S(O)_tOR^a(where t is 1 or 2), —S(O)_tN(R^a)₂(where t is 1 or 2), or —PO(OR^a)₂where each R^ais independently hydrogen and C_1-3alkyl; and

—NR¹R²is selected from: