IP Library › Granted Patent US 12,492,172

Granted Patent B2

US 12,492,172 · App. 17/785,648 · Granted Dec 9, 2025

Substituted quinazolinyl compounds useful as T cell activators

Inventors: Upender Velaparthi (Princeton Junction, NJ); Richard E. Olson (Cambridge, MA); Jayakumar Sankara Warrier (Bangalore, IN); Hasibur Rahaman (Bangalore, IN)

Assignee: Bristol-Myers Squibb Company

C07D239/80

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Quick Facts

Patent No.: US 12,492,172
App. No.: 17/785,648
Granted: Dec 9, 2025
Kind: B2

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Abstract

Disclosed are compounds of Formula (I): (I) or a salt thereof, wherein: R 1 , R 2 , R 4 , R 5 , R 6 , and m are defined herein. Also disclosed are methods of using such compounds to inhibit the activity of one or both of diacylglycerol kinase alpha (DGKα) and diacylglycerol kinase zeta (DGKζ), and pharmaceutical compositions comprising such compounds. These compounds are useful in the treatment of viral infections and proliferative disorders, such as cancer.

Claims (81)

1 . A compound of Formula (I):

or a salt thereof, wherein:

R 1 is F, Cl, Br, —CN, C 1-3 alkyl substituted with zero to 4 R 1a , C 3-4 cycloalkyl substituted with zero to 4 R 1a , C 1-3 alkoxy substituted with zero to 4 R 1a , —C(O)NR a R a , —NR a R a , —S(O) n R e , or —P(O)R e R e ;

each R 1a is independently F, Cl, —CN, —OH, —OCH 3 , or —NR a R a ;

each R a is independently H or C 1-3 alkyl;

each R e is independently C 3-4 cycloalkyl or C 1-3 alkyl substituted with zero to 4 R 1a ;

R 2 is H, C 1-3 alkyl substituted with zero to 4 R 2a , C 2-3 alkenyl substituted with zero to 4 R 2a , or C 3-4 cycloalkyl substituted with zero to 4 R 2a ;

each R 2a is independently F, Cl, —CN, —OH, —O(C 1-2 alkyl), C 3-4 cycloalkyl, C 3-4 alkenyl, or C 3-4 alkynyl;

R 4 is —CH 2 R 4a , —CH 2 CH 2 R 4a , —CH 2 CHR 4a R 4d , —CHR 4a R 4b , or —CR 4a R 4b R 4c ;

R 4a and R 4b are independently:

(i) C 1-6 alkyl substituted with zero to 4 substituents independently selected from F, Cl, —CN, —OH, —OCH 3 , —SCH 3 , C 1-3 fluoroalkoxy, —NR a R a , —S(O) 2 R e , or —NR a S(O) 2 R e ;

(ii) C 3-6 cycloalkyl, heterocyclyl, phenyl, or heteroaryl, each substituted with zero to 4 substituents independently selected from F, Cl, Br, —CN, —OH, C 1-6 alkyl, C 1-3 fluoroalkyl, C 1-4 hydroxyalkyl, —(CH 2 ) 1-2 O(C 1-3 alkyl), C 1-4 alkoxy, —O(C 1-4 hydroxyalkyl), —O(CH) 1-3 O(C 1-3 alkyl), C 1-3 fluoroalkoxy, —O(CH) 1-3 NR c R c , —OCH 2 CH═CH 2 , —OCH 2 C≡CH, —C(O)(C 1-4 alkyl), —C(O)OH, —C(O)O(C 1-4 alkyl), —NR c R c , —NR a S(O) 2 (C 1-3 alkyl), —NR a C(O)(C 1-3 alkyl), —NR a C(O)O(C 1-4 alkyl), —P(O)(C 1-3 alkyl) 2 , —S(O) 2 (C 1-3 alkyl), —O(CH 2 ) 1-2 (C 3-6 cycloalkyl), —O(CH 2 ) 1-2 (morpholinyl), cyclopropyl, cyanocyclopropyl, methylazetidinyl, acetylazetidinyl, (tert-butoxycarbonyl) azetidinyl, triazolyl, tetrahydropyranyl, morpholinyl, thiophenyl, methylpiperidinyl, and R d ; or

(iii) C 1-4 alkyl substituted with one cyclic group selected from C 3-6 cycloalkyl, heterocyclyl, aryl, and heteroaryl, said cyclic group substituted with zero to 3 substituents independently selected from F, Cl, Br, —OH, —CN, C 1-6 alkyl, C 1-3 fluoroalkyl, C 1-3 alkoxy, C 1-3 fluoroalkoxy, —OCH 2 CH═CH 2 , —OCH 2 C≡CH, —NR c R c , —NR a S(O) 2 (C 1-3 alkyl), —NR a C(O)(C 1-3 alkyl), —NR a C(O)O(C 1-4 alkyl), and C 3-6 cycloalkyl;

or R 4a and R 4b together with the carbon atom to which they are attached form a C 3-6 cycloalkyl or a 3- to 6-membered heterocyclyl, each substituted with zero to 3 R f ;

each R f is independently F, Cl, Br, —OH, —CN, C 1-6 alkyl, C 1-3 fluoroalkyl, C 1-3 alkoxy, C 1-3 fluoroalkoxy, —OCH 2 CH═CH 2 , —OCH 2 C≡CH, —NR c R c , or a cyclic group selected from C 3-6 cycloalkyl, 3- to 6-membered heterocyclyl, phenyl, monocyclic heteroaryl, and bicyclic heteroaryl, each cyclic group substituted with zero to 3 substituents independently selected from F, Cl, Br, —OH, —CN, C 1-6 alkyl, C 1-3 fluoroalkyl, C 1-3 alkoxy, C 1-3 fluoroalkoxy, and —NR c R c ;

R 4c is C 1-6 alkyl or C 3-6 cycloalkyl, each substituted with zero to 4 substituents independently selected from F, Cl, —OH, C 1-2 alkoxy, C 1-2 fluoroalkoxy, and —CN;

R 4d is —OCH 3 ;

each R c is independently H or C 1-2 alkyl;

R d is phenyl substituted with zero to 1 substituent selected from F, Cl, —CN, —CH 3 , and —OCH 3 ;

each R 5 is independently F, Cl, —CN, —OH, C 1-6 alkyl substituted with zero to 4 R g , C 1-3 alkoxy substituted with zero to 4 R g , C 2-4 alkenyl substituted with zero to 4 R g , C 2-4 alkynyl substituted with zero to 4 R g , C 3-4 cycloalkyl substituted with zero to 4 R g , phenyl substituted with zero to 4 R g , oxadiazolyl substituted with zero to 3 R g , pyridinyl substituted with zero to 4 R g , —(CH 2 ) 1-2 (heterocyclyl substituted with zero to 4 R g ), —(CH 2 ) 1-2 NR c C(O)(C 1-4 alkyl), (CH 2 ) 1-2 NR c C(O)O(C 1-4 alkyl), —(CH 2 ) 1-2 NR c S(O) 2 (C 1-4 alkyl), —C(O)(C 1-4 alkyl), —C(O)OH, —C(O)O(C 1-4 alkyl), —C(O)O(C 3-4 cycloalkyl), —C(O)NR a R a , or —C(O)NR a (C 3-4 cycloalkyl), or two R 5 attached to the same carbon atom form ═O;

each R g is independently F, Cl, —CN, —OH, C 1-3 alkoxy, C 1-3 fluoroalkoxy, —O(CH 2 ) 1-2 O(C 1-2 alkyl), C 3-5 cycloalkyl, or —NR c R c ;

each R 6 is H, F, Cl, —CN, —CH 3 , —CH 2 F, —CHF 2 , —CF 3 , or —OCH 3 ;

m is zero, 1, 2, or 3; and

n is zero, 1, or 2.

2 . The compound according to claim 1 or a salt thereof, wherein:

R 1 is F, Cl, Br, —CN, C 1-3 alkyl substituted with zero to 4 R 1a , cyclopropyl substituted with zero to 3 R 1a , C 1-3 alkoxy substituted with zero to 3 R 1a , —C(O)NR a R a , —NR a R a , —S(O) n CH 3 , or —P(O)(CH 3 ) 2 ;

each R 1a is independently F, Cl, or —CN;

each R a is independently H or C 1-3 alkyl;

R 2 is H, C 1-2 alkyl substituted with zero to 2 R 2a , or C 2-3 alkenyl substituted with zero to 2 R 2a ;

each R 2a is independently F, Cl, —CN, —OH, —O(C 1-2 alkyl), cyclopropyl, C 3-4 alkenyl, or C 3-4 alkynyl;

R 4a and R 4b are independently:

(i) C 1-4 alkyl substituted with zero to 4 substituents independently selected from F, Cl, —CN, —OH, —OCH 3 , —SCH 3 , C 1-3 fluoroalkoxy, and —NR a R a ;

(ii) C 3-6 cycloalkyl, heterocyclyl, phenyl, or heteroaryl, each substituted with zero to 4 substituents independently selected from F, Cl, Br, —CN, —OH, C 1-6 alkyl, C 1-3 fluoroalkyl, —CH 2 OH, —(CH 2 ) 1-2 O(C 1-2 alkyl), C 1-4 alkoxy, —O(C 1-4 hydroxyalkyl), —O(CH) 1-2 O(C 1-2 alkyl), C 1-3 fluoroalkoxy, —O(CH) 1-2 NR c R c , —OCH 2 CH═CH 2 , —OCH 2 C≡CH, —C(O)(C 1-4 alkyl), —C(O)OH, —C(O)O(C 1-4 alkyl), —NR c R c , —NR a S(O) 2 (C 1-3 alkyl), —NR a C(O)(C 1-3 alkyl), —NR a C(O)O(C 1-4 alkyl), —P(O)(C 1-2 alkyl) 2 , —S(O) 2 (C 1-3 alkyl), —O(CH 2 ) 1-2 (C 3-4 cycloalkyl), —O(CH 2 ) 1-2 (morpholinyl), cyclopropyl, cyanocyclopropyl, methylazetidinyl, acetylazetidinyl, (tert-butoxycarbonyl) azetidinyl, triazolyl, tetrahydropyranyl, morpholinyl, thiophenyl, methylpiperidinyl, and R d ; or

(iii) C 1-3 alkyl substituted with one cyclic group selected from C 3-6 cycloalkyl, heterocyclyl, phenyl, and heteroaryl, said cyclic group substituted with zero to 3 substituents independently selected from F, Cl, Br, —OH, —CN, C 1-3 alkyl, C 1-2 fluoroalkyl, C 1-3 alkoxy, C 1-2 fluoroalkoxy, —OCH 2 CH═CH 2 , —OCH 2 C≡CH, —NR c R c , —NR a S(O) 2 (C 1-3 alkyl), —NR a C(O)(C 1-3 alkyl), —NR a C(O)O(C 1-4 alkyl), and C 3-4 cycloalkyl;

or R 4a and R 4b together with the carbon atom to which they are attached, form a C 3-6 cycloalkyl or a 3- to 6-membered heterocyclyl, each substituted with zero to 3 R f ;

each R f is independently F, Cl, Br, —OH, —CN, C 1-4 alkyl, C 1-2 fluoroalkyl, C 1-3 alkoxy, C 1-2 fluoroalkoxy, —OCH 2 CH═CH 2 , —OCH 2 C≡CH, —NR c R c , or a cyclic group selected from C 3-6 cycloalkyl, 3- to 6-membered heterocyclyl, phenyl, monocyclic heteroaryl, and bicyclic heteroaryl, each cyclic group substituted with zero to 3 substituents independently selected from F, Cl, Br, —OH, —CN, C 1-4 alkyl, C 1-2 fluoroalkyl, C 1-3 alkoxy, C 1-2 fluoroalkoxy, and —NR c R c ;

R 4c is C 1-4 alkyl or C 3-6 cycloalkyl, each substituted with zero to 4 substituents independently selected from F, Cl, —OH, C 1-2 alkoxy, C 1-2 fluoroalkoxy, and —CN;

each R 5 is independently F, —CN, —OH, C 1-5 alkyl substituted with zero to 4 R g , C 1-2 alkoxy substituted with zero to 3 R g , C 2-3 alkenyl substituted with zero to 4 R g , C 2-3 alkynyl substituted with zero to 4 R g , C 3-4 cycloalkyl substituted with zero to 4 R g , phenyl substituted with zero to 3 R g , oxadiazolyl substituted with zero to 3 R g , pyridinyl substituted with zero to 3 R g , —(CH 2 ) 1-2 (heterocyclyl substituted with zero to 4 R g ), —(CH 2 ) 1-2 NR c C(O)(C 1-4 alkyl), (CH 2 ) 1-2 NR c C(O)O(C 1-4 alkyl), —(CH 2 ) 1-2 NR c S(O) 2 (C 1-4 alkyl), —C(O)(C 1-4 alkyl), —C(O)OH, —C(O)O(C 1-4 alkyl), —C(O)O(C 3-4 cycloalkyl), —C(O)NR a R a , or —C(O)NR a (C 3-4 cycloalkyl), or two R 5 attached to the same carbon atom form ═O;

each R 6 is H, F, or —CH 3 ; and

m is zero, 1, 2, or 3.

3 . The compound according to claim 1 or a salt thereof, wherein:

R 1 is F, —CN, or —OCH 3 ;

R 2 is H, —CH 3 , —CH 2 CN, —CH 2 CH 2 F, or —CH 2 CH═CH 2 ;

R 4 is —CH 2 R 4a or —CHR 4a R 4b ;

R 4a is phenyl, naphthalenyl, or indolyl, each substituted with zero to 2 substituents independently selected from F, —CH 3 , —CH 2 CH 3 , and —OCH 3 ;

R 4b is phenyl or fluorophenyl;

each R 5 is —CH 3 , or two R 5 attached to the same carbon atom form ═O; and

m is zero, 1, or 2.

4 . The compound according to claim 1 or a salt thereof, having the structure:

wherein R 5a and R 5c are independently selected from R 5 .

5 . The compound according to claim 1 or a salt thereof, having the structure:

6 . The compound according to claim 1 or a salt thereof, wherein R 4 is —CH 2 R 4a or —CH 2 CH 2 R 4a .

7 . The compound according to claim 1 or a salt thereof, wherein R 4 is —CH 2 R 4a .

8 . The compound according to claim 1 or a salt thereof, wherein R 4 is —CHR 4a R 4b or —CR 4a R 4b R 4c .

9 . The compound according to claim 1 or a salt thereof, wherein R 4 is —CHR 4a R 4b .

10 . The compound according to claim 1 or a salt thereof, wherein R 4 is —CH 2 R 4a or —CHR 4a R 4b .

11 . A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically-acceptable salt thereof; and a pharmaceutically acceptable carrier.

12 . A compound of Formula (I):

or a salt thereof, wherein:

R 1 is H, F, Cl, Br, —CN, C 1-3 alkyl substituted with zero to 4 R 1a , C 3-4 cycloalkyl substituted with zero to 4 R 1a , C 1-3 alkoxy substituted with zero to 4 R 1a , —C(O)NR a R a , —NR a R a , —S(O) n R e , or —P(O)R e R e ;

each R 1a is independently F, Cl, —CN, —OH, —OCH 3 , or —NR a R a ;

each R a is independently H or C 1-3 alkyl;

each R e is independently C 3-4 cycloalkyl or C 1-3 alkyl substituted with zero to 4 R 1a ;

R 2 is H, C 1-3 alkyl substituted with zero to 4 R 2a , C 2-3 alkenyl substituted with zero to 4 R 2a , or C 3-4 cycloalkyl substituted with zero to 4 R 2a ;

each R 2a is independently F, Cl, —CN, —OH, —O(C 1-2 alkyl), C 3-4 cycloalkyl, C 3-4 alkenyl, or C 3-4 alkynyl;

R 4 is —CH 2 R 4a , —CH 2 CH 2 R 4a , —CH 2 CHR 4a R 4d , —CHR 4a R 4b , or —CR 4a R 4b R 4c ;

R 4a and R 4b are independently:

(ii) C 3-6 cycloalkyl, heterocyclyl, phenyl, or heteroaryl, each substituted with zero to 4 substituents independently selected from F, Cl, Br, —CN, —OH, C 1-6 alkyl, C 1-3 fluoroalkyl, C 1-4 hydroxyalkyl, —(CH 2 ) 1-2 O(C 1-3 alkyl), C 1-4 alkoxy, —O(C 1-4 hydroxyalkyl), O(CH) 1-3 O(C 1-3 alkyl), C 1-3 fluoroalkoxy, —O(CH) 1-3 NR c R c , —OCH 2 CH═CH 2 , OCH 2 C≡CH, —C(O)(C 1-4 alkyl), —C(O)OH, —C(O)O(C 1-4 alkyl), —NR c R c , —NR a S(O) 2 (C 1-3 alkyl), —NR a C(O)(C 1-3 alkyl), —NR a C(O)O(C 1-4 alkyl), —P(O)(C 1-3 alkyl) 2 , —S(O) 2 (C 1-3 alkyl), —O(CH 2 ) 1-2 (C 3-6 cycloalkyl), —O(CH 2 ) 1-2 (morpholinyl), cyclopropyl, cyanocyclopropyl, methylazetidinyl, acetylazetidinyl, (tert-butoxycarbonyl) azetidinyl, triazolyl, tetrahydropyranyl, morpholinyl, thiophenyl, methylpiperidinyl, and R a ; or

or R 4a and R 4b together with the carbon atom to which they are attached form a C 3-6 cycloalkyl or a 3- to 6-membered heterocyclyl, each substituted with zero to 3 R f ;

R 4c is C 1-6 alkyl or C 3-6 cycloalkyl, each substituted with zero to 4 substituents independently selected from F, Cl, —OH, C 1-2 alkoxy, C 1-2 fluoroalkoxy, and —CN;

R 4d is —OCH 3 ;

each R c is independently H or C 1-2 alkyl;

R d is phenyl substituted with zero to 1 substituent selected from F, Cl, —CN, —CH 3 , and —OCH 3 ;

each R 5 is independently F, Cl, —CN, —OH, C 1-6 alkyl substituted with zero to 4 R g , C 1-3 alkoxy substituted with zero to 4 R g , C 2-4 alkenyl substituted with zero to 4 R g , C 2-4 alkynyl substituted with zero to 4 R g , C 3-4 cycloalkyl substituted with zero to 4 R g , phenyl substituted with zero to 4 R g , oxadiazolyl substituted with zero to 3 R g , pyridinyl substituted with zero to 4 R g , —(CH 2 ) 1-2 (heterocyclyl substituted with zero to 4 R g ), —(CH 2 ) 1-2 NR c C(O)(C 1-4 alkyl), (CH 2 ) 1-2 NR c C(O)O(C 1-4 alkyl), —(CH 2 ) 1-2 NR c S(O) 2 (C 1-4 alkyl), —C(O)(C 1-4 alkyl), —C(O) OH, —C(O)O(C 1-4 alkyl), —C(O)O(C 3-4 cycloalkyl), —C(O)NR a R a , or —C(O)NR a (C 3-4 cycloalkyl), or two R 5 attached to the same carbon atom form ═O;

each R g is independently F, Cl, —CN, —OH, C 1-3 alkoxy, C 1-3 fluoroalkoxy, —O(CH 2 ) 1-2 O(C 1-2 alkyl), C 3-5 cycloalkyl, or —NR c R c ;

each R 6 is H, F, Cl, —CN, —CH 3 , —CH 2 F, —CHF 2 , —CF 3 , or —OCH 3 ;

m is 1, 2, or 3; and

n is zero, 1, or 2.

Priority Claims (1)

IN 201911053553 · Dec 23, 2019 · national

Continuity (1)

Related Publication 20230094758A1 · Mar 30, 2023

References Cited (82)

US 4324893A · Scotese et al. · 1982 [cited by applicant]

US 7084141B2 · Gaeta et al. · 2006 [cited by applicant]

US 7173036B2 · Sircar et al. · 2007 [cited by applicant]

US 7220856B2 · Dunning et al. · 2007 [cited by applicant]

US 7279481B2 · Bergauer et al. · 2007 [cited by applicant]

US 7381401B2 · Gajewski · 2008 [cited by applicant]

US 9050334B2 · Gaweco et al. · 2015 [cited by applicant]

US 9133164B2 · Gaweco et al. · 2015 [cited by applicant]

US 10532042B2 · Lanman et al. · 2020 [cited by applicant]

US 10669272B2 · Velaparthi et al. · 2020 [cited by applicant]

US 20050124604A1 · Sircar et al. · 2005 [cited by applicant]

US 20050266510A1 · Gajewski · 2005 [cited by applicant]

US 20110281908A1 · Sun et al. · 2011 [cited by applicant]

US 20150224142A1 · Albelda et al. · 2015 [cited by applicant]

US 20180334454A1 · Lanman et al. · 2018 [cited by applicant]

US 20200115384A1 · Wu et al. · 2020 [cited by applicant]

US 20210061802A1 · Velaparthi et al. · 2021 [cited by applicant]

JP 6461468 · 1989 [cited by applicant]

JP S6461468 · 1989 [cited by applicant]

JP B002544939 · 1996 [cited by applicant]

JP 2544939B2 · 1996 [cited by examiner]

WO 2004056824A2 · 2004 [cited by applicant]

WO 2004074218A2 · 2004 [cited by applicant]

WO 2004087880A2 · 2004 [cited by applicant]

WO 2005009967A2 · 2005 [cited by applicant]

WO 2005021546A1 · 2005 [cited by applicant]

WO 2007109251A2 · 2007 [cited by applicant]

WO 2007132948A1 · 2007 [cited by applicant]

WO 2007136125A1 · 2007 [cited by applicant]

WO 2010042489A2 · 2010 [cited by applicant]

WO 2010088408A2 · 2010 [cited by applicant]

WO 2012009649A1 · 2012 [cited by applicant]

WO 2012142498A2 · 2012 [cited by applicant]

WO 2013118071A1 · 2013 [cited by applicant]

WO 16096631A1 · 2016 [cited by applicant]

WO 2016164675A1 · 2016 [cited by applicant]

WO 2017106607A1 · 2017 [cited by applicant]

WO 2017177037A1 · 2017 [cited by applicant]

WO 2018119183A2 · 2018 [cited by applicant]

WO 2018134685A2 · 2018 [cited by applicant]

WO 2019005883A1 · 2019 [cited by applicant]

WO 19213516A1 · 2019 [cited by applicant]

WO 2020006016A1 · 2020 [cited by applicant]

WO 2020006018A1 · 2020 [cited by applicant]

WO 2020071550A1 · 2020 [cited by applicant]

WO 2021105115A1 · 2021 [cited by applicant]

WO 2021105116 · 2021 [cited by applicant]

WO 2021105117A1 · 2021 [cited by applicant]

Abdel-Magid, “Cancer Immunotherapy through the Inhibition of Dlacylglycerol Kinases Alpha and Zeta”, ACS Med. Chem. Lett. 2020, 11,1083-1085. [cited by applicant]

Avila-Flores, A. et al., “Predominant Contribution of DGKξ over DGKα in the Control of PKC/PDK-1-Regulated Functions in T Cells”, Immunology and Cell Biology (2017) 95: 549-563. [cited by applicant]

Barraza et al., “Discovery of Anthranilamides as a Novel Class of Inhyibitors of Neurotropic Alphavirus Replication”, Bloorg. Med. Chem 23 (2015) 1569-1587. [cited by applicant]

Boroda et al., “Dual Activites of Ritanserin and R59022 as DGKα inhibitors and Serotonin Receptor Antagonists” Biochemical Pharmacology 123 (2017) 29-39. [cited by applicant]

Chen et al., “Diacyiglycerol Kinases in T Cell Tolerance and Effector Function”, Frontiers in Cell and Development Biology vol. 4 pp. 1-13, (2016). [cited by applicant]

Dagia et al., “A fluorinated Analog of ISO-1 blocks the Recognition and Biological Function of MIF and is Orally Efficacious in a Murine Model of Colitis” Eur. J. Pharmacology 607 (2009) 201-212. [cited by applicant]

Database Registry Chemical Abstracts Service: Database RN 2249638-34-2 (Entered STN Nov. 19, 2018). [cited by applicant]

Facciabene, et al. “T-Regulartory Cells: Key Players in Tumor Immune Escape and Angiogenesis” Cancer Res. 72(9) 2162-2171 (2012). [cited by applicant]

Franks et al., “The Ligand Binding Landscape of Dlacylglycerol Kinases” Cell Chem Bio 24, 870-880 (2017). [cited by applicant]

Ganesan et al., “Comprehensive in vitro Characterization of PD-L1 Small Molecule Inhibitors”, Scientific Reports 9, Article No. 12392 (2019). [cited by applicant]

IInternational Preliminary Report on Patentability for PCT Application PCT/US2020/066508, mailed Jun. 28, 2022. [cited by applicant]

Jiang et al., “Selectivity of the Diacylglycerol Kinase Inhibitor 3-2,3-dihydro-2-thioxo-4(1H)quinazolinone (R59949) among Diacylglycerol Kinase Subtypes”, Biochemochemical Pharmacology 59, 763-772, 2000. [cited by applicant]

Jing et al., “T Cells Deficient In Diacylglycerol Kinase ξ are Resistance to PD-1 Inhibition and Help Create Persistent Host Immunity to Leukemia” Cancer Res 77(20) 5676-5686 (2017). [cited by applicant]

Krishna et al., “Regulation of Lipid Signaling by Diacylglycerol Kinases During T Cell Development and Function” Front Immunolog. (2013) 4: Article 178. [cited by applicant]

Liu et al., “A Novel Diacyiglycerol Kinase a-Selective Inhibitor CU-3, Induces Cancer Cell Apoptosis and Enhances Immune Response” J. Lipid Res. 57, 368-379 (2016). [cited by applicant]

McCloud et al., “Deconstructing Lipid Kinase Inhibitors By Chemical Proteomics” Biochem. 2018, 57, 231-236. [cited by applicant]

McLean et al., “Fragment Screening of Inhibitors for MIF Tautomerase Reveals a Cryptic Surface Binding Site” Bio. Med. Chem. Lett. 20 (2010) 1821-1824. [cited by applicant]

Mellman et al. “Cancer Immunotherapy Comes of Age” Nature 480 480-489 (2011). [cited by applicant]

Merida et al., “Redundant and Specialized Roles for Diacylglycerol Kinases α and ξ in the Control of T cell Functions” Science Signaling 8 (374), re6 (2015). [cited by applicant]

Merida I., Arranz-Nicolás J., et al., “Diacylglycerol Kinase Malfunction in Human Disease and the Search for Specific Inhibitors”, Handbook of Experimental Pharmacology. Springer, Berlin, Heidelberg (2019). First Online… [cited by applicant]

Mizoguchi et al., “Alterations in Signal Transduction Molecules in T Lumphocytes from Tumor-Bearing Mice” (1992) Science 258:1795-98. [cited by applicant]

Noessner, “DGK-α: A Checkpoint in Cancer-Mediated Immuno-Inhibition and Target for Immunotherapy” Front Cell Dev Bio 2017 5, Article 16. [cited by applicant]

Olenchock et al., “Disruption of the Diacylglycerol Metabolism Impairs the Induction of T cell Anergy”, Nature Immunology 7(11) 1174-1181 (2006). [cited by applicant]

Prinz et al., “High DGK-α and Disabled MAPK Pathways Cause Dysfunction of Human Tumor-Infiltrating CD8+ T Cells that Is Reversible by Pharmacologic Intervention”, J Immunology 188(12) 5990-6000 (2012). [cited by applicant]

Purow, B. “Molecular Pathways: Targeting Diacylglycerol Kinase Aplha in Cancer” Clin. Cancer Res. 21(22) 5008-5012 (2015). [cited by applicant]

Riese et al., “Decreased Dlacylglycerol Metabolism Enhances ERK Activation and Augments DC8+ T Cell Functional Responses”, J Bio Chem 286(7) 5254-5265 (2011). [cited by applicant]

Riese et al., “Diacylglycerol Kinases (DGKs): Novel Targets for Improving T Cell Activity in Cancer” Frontiers Cell Dev Bio (2016) 4, Article 108. [cited by applicant]

Santilli et al., “2-Oxo-1,8-naphthyridine-3-carboxylic Acid Derivaties with Potent Gastric Antisecretory Properties” J. Med. Chem. 1987, 30, 2270-2277. [cited by applicant]

Sjoblom et al. “The Consensus Coding Sequences of Human Breast and Colorectal Cancers” Science 314 268-274 (2006). [cited by applicant]

Tominaga et al., “Studies on Positive Inotropic Agents. I. Synthesis of 3,4-Dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-pierazinyi]-2(1H)-quinolinone and Related Compounds”, Chem. Pharm. Bull. 32(6) 2100-2110 (1984). [cited by applicant]

Topalian et al., “Targetomg the PD-1/B7-H1 (PD-L1) Pathway to Activate Anti-tumor Immunity”, Curr. Opin. Immunol. 2012, 24:207-212. [cited by applicant]

Velnati et al., “Identification of a Novel DGKα Inhibitor for XLP-1 Therapy by Virtual Screening”, Eur J Med Chem 164 (2019) 378-390. [cited by applicant]

Wesley et al., “Diacylglycerol Kinase ξ (DGKξ) and Casitas b-Lineage Proto-Oncogene b-Deficient Mice Have Similar Functional Outcomes in T Cells but DGK ξ-Deficient Mice have Increased T Cell Activatin and Turnor Cleara… [cited by applicant]

Zha Y et al., “T Cell Anergy is Reversed by Active Ras and is Regulated by Diacylglycerol Kinase-α” Nature Immunology, (2006) 7(11) 1166-1173; Erratum 7(12) 1343. [cited by applicant]