US 12,258,314 B2
EBNA1 inhibitors and their method of use
Troy E. Messick, Upper Darby, PA (US); Garry R. Smith, Royersford, PA (US); Allen B. Reitz, Lansdale, PA (US); Paul M. Lieberman, Wynnewood, PA (US); Mark E. McDONNELL, Lansdale, PA (US); Yan Zhang, Fort Washington, PA (US); and Venkata Velvadapu, Ankeny, IA (US)
Assigned to THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, Philadelphia, PA (US)
Filed by THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, Philadelphia, PA (US)
Filed on Dec. 22, 2021, as Appl. No. 17/558,877.
Application 17/558,877 is a continuation of application No. 16/519,590, filed on Jul. 23, 2019, granted, now 11,242,317.
Application 16/519,590 is a continuation of application No. 15/814,600, filed on Nov. 16, 2017, granted, now 10,421,718, issued on Sep. 24, 2019.
Application 15/814,600 is a continuation of application No. 15/036,211, granted, now 9,856,214, issued on Jan. 2, 2018, previously published as PCT/US2014/065765, filed on Nov. 14, 2014.
Claims priority of provisional application 61/904,555, filed on Nov. 15, 2013.
Prior Publication US 2022/0396551 A1, Dec. 15, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 207/327 (2006.01); A61K 31/192 (2006.01); A61K 31/404 (2006.01); A61K 31/44 (2006.01); A61K 31/4439 (2006.01); A61K 31/496 (2006.01); C07C 53/18 (2006.01); C07C 63/66 (2006.01); C07C 65/19 (2006.01); C07C 65/28 (2006.01); C07C 211/27 (2006.01); C07C 217/84 (2006.01); C07C 229/56 (2006.01); C07C 229/64 (2006.01); C07C 233/11 (2006.01); C07C 233/64 (2006.01); C07C 233/65 (2006.01); C07C 235/58 (2006.01); C07C 255/54 (2006.01); C07C 255/55 (2006.01); C07C 311/08 (2006.01); C07C 311/16 (2006.01); C07C 311/17 (2006.01); C07C 317/14 (2006.01); C07C 317/44 (2006.01); C07D 207/08 (2006.01); C07D 207/12 (2006.01); C07D 207/14 (2006.01); C07D 207/16 (2006.01); C07D 209/08 (2006.01); C07D 211/70 (2006.01); C07D 213/55 (2006.01); C07D 213/64 (2006.01); C07D 213/74 (2006.01); C07D 215/14 (2006.01); C07D 231/12 (2006.01); C07D 235/06 (2006.01); C07D 239/26 (2006.01); C07D 249/06 (2006.01); C07D 277/30 (2006.01); C07D 295/155 (2006.01); C07D 307/79 (2006.01); C07D 333/54 (2006.01); C07D 401/04 (2006.01); C07D 401/10 (2006.01); C07D 403/10 (2006.01); C07D 409/10 (2006.01); C07D 417/10 (2006.01); C07D 471/04 (2006.01); C07D 487/04 (2006.01)
CPC C07D 207/327 (2013.01) [A61K 31/192 (2013.01); A61K 31/404 (2013.01); A61K 31/44 (2013.01); A61K 31/4439 (2013.01); A61K 31/496 (2013.01); C07C 53/18 (2013.01); C07C 63/66 (2013.01); C07C 65/19 (2013.01); C07C 65/28 (2013.01); C07C 211/27 (2013.01); C07C 217/84 (2013.01); C07C 229/56 (2013.01); C07C 229/64 (2013.01); C07C 233/11 (2013.01); C07C 233/64 (2013.01); C07C 233/65 (2013.01); C07C 235/58 (2013.01); C07C 255/54 (2013.01); C07C 255/55 (2013.01); C07C 311/08 (2013.01); C07C 311/16 (2013.01); C07C 311/17 (2013.01); C07C 317/14 (2013.01); C07C 317/44 (2013.01); C07D 207/08 (2013.01); C07D 207/12 (2013.01); C07D 207/14 (2013.01); C07D 207/16 (2013.01); C07D 209/08 (2013.01); C07D 211/70 (2013.01); C07D 213/55 (2013.01); C07D 213/64 (2013.01); C07D 213/74 (2013.01); C07D 215/14 (2013.01); C07D 231/12 (2013.01); C07D 235/06 (2013.01); C07D 239/26 (2013.01); C07D 249/06 (2013.01); C07D 277/30 (2013.01); C07D 295/155 (2013.01); C07D 307/79 (2013.01); C07D 333/54 (2013.01); C07D 401/04 (2013.01); C07D 401/10 (2013.01); C07D 403/10 (2013.01); C07D 409/10 (2013.01); C07D 417/10 (2013.01); C07D 471/04 (2013.01); C07D 487/04 (2013.01); C07C 2601/02 (2017.05)] 7 Claims
 
1. A method of treating or ameliorating a disease caused by EBNA1 activity in a subject, wherein the disease caused by EBNA1 activity is at least one selected from the group consisting of infectious mononucleosis, chronic fatigue syndrome, multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis,
the method comprising administering to the subject a therapeutically effective amount of a compound of formula (IX):

OG Complex Work Unit Chemistry
or a solvate or salt thereof, wherein:
R1 is selected from the group consisting of optionally substituted thiazolyl, optionally substituted pyridyl, optionally substituted benzyl,

OG Complex Work Unit Chemistry
R2 is

OG Complex Work Unit Chemistry
R3 is CO2R4d;
R4d is selected from the group consisting of hydrogen, optionally substituted C1-6 linear alkyl, and optionally substituted C3-6 branched alkyl;
R8a, R8b, R8c, R8d, and R8e are each independently selected from the group consisting of hydrogen, optionally substituted C1-6 linear alkyl, and optionally substituted C3-6 branched alkyl;
R9a, R9b, R9c, R9d, and R9e are each independently selected from the group consisting of hydrogen, optionally substituted C1-6 linear alkyl, and optionally substituted C3-6 branched alkyl;
L2 is (CH2)m; and
m is 0, 1, 2, or 3.