US 12,459,967 B2
Modulators of 5′-nucleotidase, ecto and the use thereof
Laurent Pierre Paul Debien, San Francisco, CA (US); Juan Carlos Jaen, Burlingame, CA (US); Jaroslaw Kalisiak, Newark, CA (US); Kenneth V. Lawson, San Francisco, CA (US); Manmohan Reddy Leleti, Dublin, CA (US); Erick Allen Lindsey, San Diego, CA (US); Dillon Harding Miles, Berkeley, CA (US); Eric Newcomb, Boulder, CO (US); Jay Patrick Powers, Sisters, OR (US); Brandon Reid Rosen, San Mateo, CA (US); and Ehesan Ui Sharif, Castro Valley, CA (US)
Assigned to Arcus Biosciences, Inc., Hayward, CA (US)
Filed by Arcus Biosciences, Inc., Hayward, CA (US)
Filed on Nov. 21, 2023, as Appl. No. 18/516,459.
Application 18/516,459 is a continuation of application No. 18/298,174, filed on Apr. 10, 2023, abandoned.
Application 18/298,174 is a continuation of application No. 17/206,896, filed on Mar. 19, 2021, granted, now 11,667,662, issued on Jun. 6, 2023.
Application 17/206,896 is a continuation of application No. 17/009,590, filed on Sep. 1, 2020, granted, now 11,001,603, issued on May 11, 2021.
Application 17/009,590 is a continuation of application No. 16/273,843, filed on Feb. 12, 2019, granted, now 10,981,944, issued on Apr. 20, 2021.
Application 16/273,843 is a continuation of application No. 15/400,748, filed on Jan. 6, 2017, granted, now 10,239,912, issued on Mar. 26, 2019.
Claims priority of provisional application 62/324,077, filed on Apr. 18, 2016.
Claims priority of provisional application 62/276,564, filed on Jan. 8, 2016.
Prior Publication US 2024/0352057 A1, Oct. 24, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07H 19/23 (2006.01); A61K 31/70 (2006.01); A61K 31/7052 (2006.01); A61K 31/706 (2006.01); A61K 31/7064 (2006.01); A61K 31/7076 (2006.01); A61K 45/06 (2006.01); C07F 9/6561 (2006.01); C07H 19/04 (2006.01); C07H 19/14 (2006.01); C07H 19/16 (2006.01); C07H 19/20 (2006.01); C07H 19/207 (2006.01)
CPC C07H 19/23 (2013.01) [A61K 31/70 (2013.01); A61K 31/7052 (2013.01); A61K 31/706 (2013.01); A61K 31/7064 (2013.01); A61K 31/7076 (2013.01); A61K 45/06 (2013.01); C07F 9/6561 (2013.01); C07F 9/65616 (2013.01); C07H 19/04 (2013.01); C07H 19/14 (2013.01); C07H 19/16 (2013.01); C07H 19/20 (2013.01); C07H 19/207 (2013.01)] 11 Claims
 
1. A compound having the formula:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein,
each R1 is independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted aryl, and —C(R2R2)—O—C(O)—OR3, or two R1 groups are optionally combined to form a 5- to 7-membered ring;
each R2 is independently selected from the group consisting of H and optionally substituted C1-C6alkyl;
each R3 is independently selected from the group consisting of H, C1-C6 alkyl, and optionally substituted aryl;
R5 is selected from the group consisting of H and optionally substituted C1-C6 alkyl;
X is selected from the group consisting of O, CH2, and S;
A is selected from the group consisting of:

OG Complex Work Unit Chemistry
each of which is optionally substituted with from 1 to 5 R6 substituents, and wherein the subscript n is an integer from 0 to 3;
Z is selected from the group consisting of CH2, CHR6, NR6, and O;
each R6 is independently selected from the group consisting of H, CH3, OH, CN, F, optionally substituted C1-C6 alkyl, and OC(O)—C1-C6 alkyl; and optionally two R6 groups on adjacent ring vertices are joined together to form a 5- to 6-membered ring having at least one heteroatom as a ring vertex; and
Het is selected from the group consisting of:

OG Complex Work Unit Chemistry
wherein the wavy line indicates the point of attachment to the remainder of the compound, and wherein:
Ra is selected from the group consisting of H, NH2, NHR7, NHC(O)R7, NR7R7, R7, OH, SR7, and OR7;
Rb is selected from the group consisting of H, halogen, NH2, NHR7, NR7R7, R7, OH, and OR7;
Rc is selected from the group consisting of H, halogen, haloalkyl, NH2, NHR7, NR7R7, R7, OH, OR7, SR7, SO2R7, —X1—NH2, —X1—NHR7, —X1—NR7R7, —X1—OH, —X1—OR7, —X1—SR7, and —X1—SO2R7;
Re and Rf are independently selected from the group consisting of H, halogen, and optionally substituted C1-C6 alkyl;
each X1 is C1-C4alkylene; and
each R7 is independently selected from the group consisting of optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, optionally substituted C3-C7 cycloalkyl, optionally substituted C3-C7 cycloalkylC1-C4alkyl, optionally substituted 4-7 membered cycloheteroalkyl, optionally substituted 4-7 membered cycloheteroalkylC1-C4alkyl, optionally substituted aryl, optionally substituted arylC1-C4alkyl, optionally substituted arylC2-C4alkenyl, optionally substituted arylC2-C4alkynyl, optionally substituted heteroaryl, optionally substituted heteroarylC1-C4alkyl, optionally substituted heteroarylC1-C4alkenyl, optionally substituted heteroarylC2-C4alkynyl, and optionally, two R7 groups attached to a nitrogen atom are joined together to form a 4- to 7-membered heterocyclic ring, optionally fused to an aryl ring.