US 12,145,927 B2
Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
James Aaron Balog, Princeton, NJ (US); Steven P. Seitz, Princeton, NJ (US); Jay A. Markwalder, Princeton, NJ (US); David K. Williams, Princeton, NJ (US); Weifang Shan, Princeton, NJ (US); Susheel Jethanand Nara, Bangalore (IN); Saumya Roy, Bangalore (IN); Srinivas Cheruku, Bangalore (IN); and Nagalakshmi Pulicharla, Bangalore (IN)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Appl. No. 17/261,968
Filed by BRISTOL-MYERS SQUIBB COMPANY, Princeton, NJ (US)
PCT Filed Jul. 22, 2019, PCT No. PCT/US2019/042773
§ 371(c)(1), (2) Date Jan. 21, 2021,
PCT Pub. No. WO2020/023356, PCT Pub. Date Jan. 30, 2020.
Claims priority of provisional application 62/701,895, filed on Jul. 23, 2018.
Prior Publication US 2021/0355113 A1, Nov. 18, 2021
Int. Cl. C07D 405/14 (2006.01); C07D 307/79 (2006.01); C07D 313/08 (2006.01); C07D 405/10 (2006.01); C07D 413/10 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01); C07K 16/28 (2006.01)
CPC C07D 405/14 (2013.01) [C07D 307/79 (2013.01); C07D 313/08 (2013.01); C07D 405/10 (2013.01); C07D 413/10 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07K 16/2818 (2013.01)] 11 Claims
 
1. A compound of formula (I):

OG Complex Work Unit Chemistry
wherein:
A is —CR7R8—, —CR9R10CR11R12—, —CR13R14CR15R16CHR17—, or —CR14═CR16CHR17—;
Q is (C2-C6 alkyl substituted with (C(O)OH and R3), (C3-C6 cycloalkyl substituted with W) or (phenyl substituted with W and R3);
X is a bond, C(O), —C(O)CR4R5— or —C(O)NR6—;
W is selected from: C(O)ORa, C(O)NH2, —S(O)2NHRb,

OG Complex Work Unit Chemistry
R1 is selected from: C1-C6 alkyl, C3-C6 cycloalkyl, tetrahydro-2H-pyranyl, morpholinyl, phenyl, naphthalenyl, thiophenyl, thiazolyl, isoxazolyl, 1H-imidazolyl, pyrazolyl, 1,2,4-oxadiazolyl, 1,3,4-thiadiazolyl, 1H-tetrazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, benzo[b]thiophenyl, benzo[d]thiazolyl, benzo[d]oxazolyl, benzo[d]imidazolyl, pyrazolo[1,5-a]pyrimidinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, 7H-pyrrolo[2,3-d]pyrimidinyl, and quinolin-2-yl; wherein each moiety is substituted with 0 to 2Rc;
R2 is selected from: C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, and (phenyl substituted with 0 to 2 Rd);
R3 is independently H, halo, C1-C4 alkyl, C1-C4 halolkyl, C1-C4 alkoxy or C1-C4 halolkoxy;
R4 and R5 are independently H, halo, or C1-C4 alkyl;
R6 is H or C-C4 alkyl;
R7 is H, halo, C1-C4 alkyl, C2-C4 alkenyl, or cyclopropyl;
R8 is H, halo, or C1-C4 alkyl;
R9, R10, R11 and R12 are H, halo, or C1-C4 alkyl;
R13 and R15 are independently H, OH, halo or C1-C4 alkyl;
R14, R16 and R17 are independently H, halo or C1-C4 alkyl;
Ra is H or C1-C6 alkyl;
Rb is H, or C(O)(C1-C4 alkyl), or C(O)Ph;
Rc is independently selected from: halo, CN, C1-C6 alkyl, C1-C6 halolkyl, C1-C6, alkoxy, C1-C6 halolkoxy, CH2OH, C(O)OH, C(O)NH2, —S(O)2(C1-C4 alkyl), C3-C6 cycloalkyl, and (phenyl substituted with 0 to 2 Re); and
Rd and Re are independently selected from halo, C1-C4 alkyl, C1-C4 halolkyl, C1-C4 alkoxy and C1-C4 halolkoxy;
or a pharmaceutically acceptable salt thereof.