US 11,866,430 B2
Naphthyridinone compounds useful as T cell activators
Louis S. Chupak, Old Saybrook, CT (US); Min Ding, Stow, MA (US); Robert G. Gentles, Killingworth, CT (US); Yazhong Huang, Wallingford, CT (US); Scott W. Martin, Middletown, CT (US); Ivar M. Mcdonald, Woodstock, CT (US); Stephen E. Mercer, Wakefield, MA (US); Richard E. Olson, Cambridge, MA (US); Upender Velaparthi, Princeton Junction, NJ (US); Michael Wichroski, Yardley, PA (US); and Xiaofan Zheng, Cheshire, CT (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Appl. No. 17/254,914
Filed by BRISTOL-MYERS SQUIBB COMPANY, Princeton, NJ (US)
PCT Filed Jun. 26, 2019, PCT No. PCT/US2019/039131
§ 371(c)(1), (2) Date Dec. 22, 2020,
PCT Pub. No. WO2020/006016, PCT Pub. Date Jan. 2, 2020.
Claims priority of provisional application 62/690,444, filed on Jun. 27, 2018.
Prior Publication US 2021/0277004 A1, Sep. 9, 2021
Int. Cl. C07D 471/04 (2006.01); A61K 31/4375 (2006.01); A61P 35/00 (2006.01)
CPC C07D 471/04 (2013.01) [A61K 31/4375 (2013.01); A61P 35/00 (2018.01)] 11 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a salt thereof, wherein:
R1 is H, Cl, Br, —CN, C1-4 alkyl, C2-3 alkenyl, C1-3 alkoxy, —C(O)OH, —C(O)O(C1-3 alkyl), —C(O)NRaRa, —NRaRa, —NRaC(O)O(C1-4 alkyl), or —NRaC(O)NRa(C1-4 alkyl);
each Ra is independently H or C1-2 alkyl;
R2 is C1-6 alkyl, C1-4 cyanoalkyl, C1-4 fluoroalkyl, C2-4 alkenyl, —(CH2)1-3CH═CF2, C3-5 alkynyl, —(CH2)1-4O(C1-3 alkyl), —(CH2)1-4O(CH2)1-3O(C1-3 alkyl), —(CH2)1-3C(O)(C1-3 alkyl), —(CH2)1-3C(O)O(C1-3 alkyl), —(CH2)1-3Rb, —(CH2)1-3ORb, or —(CH2)1-3OCH2Rb;
Rb is C3-6 cycloalkyl or dioxanyl, each substituted with zero to 2 substituents independently selected from F, —CN, —CH3, and —OCH3;
R3 is H, F, Cl, Br, —CN, C1-3 alkyl, C1-3 fluoroalkyl, —NO2, —C(O)(C1-3 alkyl), —C(O)O(C1-3 alkyl), or —C(O)(C1-3 fluoroalkyl);
R4 is:
(a) 2,3-dihydro-1H-indenyl substituted with zero to 2 substituents independently selected from F, Cl, —OH, C1-2 alkyl, C1-2 fluoroalkyl, C1-2 alkoxy, and —OCH2CH═CH2; or
(b) —CH2Ry, —C(CH3)2Ry, —CHRxRy, —CH2CH(OH)Rx, —CH(CH3)(CH2CH2OCH3), or C3-6 cycloalkyl substituted with fluorophenyl;
Rx is C1-6 alkyl, C1-3 hydroxyalkyl, C1-2 aminoalkyl, C3-6 cycloalkyl, or phenyl substituted with zero to 2 substituents independently selected from F, Cl, —OH, C1-3 alkyl, C1-2 fluoroalkyl, C1-2 alkoxy, —OCH2CH═CH2, and —OCH2C≡CH;
Ry is 1,3-benzodiazolyl, indazolyl, indolyl, indolinyl, naphthalenyl, oxoindolinyl, pyridinyl, pyrimidinyl, or phenyl, each substituted with zero to 3 substituents independently selected from F, Cl, Br, —OH, —CN, C1-6 alkyl, C1-3 fluoroalkyl, C1-3 alkoxy, C1-3 fluoroalkoxy, —OCH2CH═CH2, —OCH2C≡CH, —OCH2(cyanopyridinyl), —NRcRc, —NRaS(O)2(C1-3 alkyl), —NRaC(O)(C1-3 alkyl), —NRaC(O)O(C1-4 alkyl), —NRaC(O)Rd, —NRaC(O)NRaRd, and Rd;
each Rc is independently H or C1-2 alkyl; and
Rd is phenyl substituted with zero to 1 substituent selected from Cl, —CH3, and —OCH3.