Granted Patent B2

US 12,459,967 · App. 18/516,459 · Granted Nov 4, 2025

Inventors: Laurent Pierre Paul Debien (San Francisco, CA); Juan Carlos Jaen (Burlingame, CA); Jaroslaw Kalisiak (Newark, CA); Kenneth V. Lawson (San Francisco, CA); Manmohan Reddy Leleti (Dublin, CA); Erick Allen Lindsey (San Diego, CA); Dillon Harding Miles (Berkeley, CA); Eric Newcomb (Boulder, CO); Jay Patrick Powers (Sisters, OR); Brandon Reid Rosen (San Mateo, CA); Ehesan Ui Sharif (Castro Valley, CA)

Assignee: Arcus Biosciences, Inc.

C07H19/23A61K31/70A61K31/7052A61K31/706A61K31/7064A61K31/7076A61K45/06C07F9/6561C07F9/65616C07H19/04C07H19/14C07H19/16C07H19/20C07H19/207

Abstract

Claims (46)

1. A compound having the formula:

or a pharmaceutically acceptable salt thereof, wherein,

each R 1 is independently selected from the group consisting of hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted aryl, and —C(R 2 R 2 )—O—C(O)—OR 3 , or two R 1 groups are optionally combined to form a 5- to 7-membered ring;

each R 2 is independently selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl;

each R 3 is independently selected from the group consisting of H, C 1 -C 6 alkyl, and optionally substituted aryl;

R 5 is selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl;

X is selected from the group consisting of O, CH 2 , and S;

A is selected from the group consisting of:

each of which is optionally substituted with from 1 to 5 R 6 substituents, and wherein the subscript n is an integer from 0 to 3;

Z is selected from the group consisting of CH 2 , CHR 6 , NR 6 , and O;

each R 6 is independently selected from the group consisting of H, CH 3 , OH, CN, F, optionally substituted C 1 -C 6 alkyl, and OC(O)—C 1 -C 6 alkyl; and optionally two R 6 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:

wherein the wavy line indicates the point of attachment to the remainder of the compound, and wherein:

R a is selected from the group consisting of H, NH 2 , NHR 7 , NHC(O)R 7 , NR 7 R 7 , R 7 , OH, SR 7 , and OR 7 ;

R b is selected from the group consisting of H, halogen, NH 2 , NHR 7 , NR 7 R 7 , R 7 , OH, and OR 7 ;

R c is selected from the group consisting of H, halogen, haloalkyl, NH 2 , NHR 7 , NR 7 R 7 , R 7 , OH, OR 7 , SR 7 , SO 2 R 7 , —X 1 —NH 2 , —X 1 —NHR 7 , —X 1 —NR 7 R 7 , —X 1 —OH, —X 1 —OR 7 , —X 1 —SR 7 , and —X 1 —SO 2 R 7 ;

R e and R f are independently selected from the group consisting of H, halogen, and optionally substituted C 1 -C 6 alkyl;

each X 1 is C 1 -C 4 alkylene; and

each R 7 is independently selected from the group consisting of optionally substituted C 1 -C 10 alkyl, optionally substituted C 2 -C 10 alkenyl, optionally substituted C 2 -C 10 alkynyl, optionally substituted C 3 -C 7 cycloalkyl, optionally substituted C 3 -C 7 cycloalkylC 1 -C 4 alkyl, optionally substituted 4-7 membered cycloheteroalkyl, optionally substituted 4-7 membered cycloheteroalkylC 1 -C 4 alkyl, optionally substituted aryl, optionally substituted arylC 1 -C 4 alkyl, optionally substituted arylC 2 -C 4 alkenyl, optionally substituted arylC 2 -C 4 alkynyl, optionally substituted heteroaryl, optionally substituted heteroarylC 1 -C 4 alkyl, optionally substituted heteroarylC 1 -C 4 alkenyl, optionally substituted heteroarylC 2 -C 4 alkynyl, and optionally, two R 7 groups attached to a nitrogen atom are joined together to form a 4- to 7-membered heterocyclic ring, optionally fused to an aryl ring.

2. The compound of claim 1 , wherein R 5 is H, X is O, each R 1 is H, R e is H, and R a is selected from the group consisting of NH 2 , NHR 7 , and N(R 7 ) 2 .

3. The compound of claim 1 , wherein R 5 is H, X is O, each R 1 is H, R e is H, R c is other than H, and R a is NHR 7 .

4. A compound having the formula:

or a pharmaceutically acceptable salt thereof, wherein,

each R 1 is independently selected from the group consisting of hydrogen and —C(R 2 R 2 )—O—C(O)—OR 3 ;

each R 2 is H;

each R 3 is independently selected from the group consisting of H and C 1 -C 6 alkyl;

R 5 is H;

X is O;

A is

 optionally substituted with from 1 to 5 R 6 substituents;

Z is O;

each R 6 is independently selected from the group consisting of H, OH, and F;

Het is

 wherein the wavy line indicates the point of attachment to the remainder of the compound, and wherein:

R a is selected from the group consisting of NHR 7 and NR 7 R 7 ;

R b is H;

R c is H or halogen;

R e is H; and

each R 7 is independently selected from the group consisting of C 1 -C 10 alkyl, C 3 -C 7 cycloalkyl, 4-7 membered cycloheteroalkyl, and optionally substituted arylC 1 -C 4 alkyl; wherein the aryl is optionally substituted with halogen in a number up to the total number of open valences.

5. The compound of claim 4 , wherein A is selected from the group consisting of:

6. The compound of claim 4 , each R 1 is H.

7. The compound of claim 4 , wherein R a is N(R 7 ) 2 .

8. The compound of claim 4 , wherein R a is NHR 7 .

9. A compound which is:

10. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

11. A pharmaceutical composition comprising a compound of claim 4 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

Assignments (1)

Continuity (8)

References Cited (83)