US 11,952,434 B2
Immunomodulators
Kevin W. Gillman, Madison, CT (US); Jason Goodrich, Wallingford, CT (US); Kenneth M. Boy, Southborough, MA (US); Yunhui Zhang, Princeton, NJ (US); Claudio Mapelli, Linden, NJ (US); Michael A. Poss, Lawrenceville, NJ (US); Paul Michael Scola, Glastonbury, CT (US); David R. Langley, Meriden, CT (US); and Nicholas A. Meanwell, Yardley, PA (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Filed by Bristol-Myers Squibb Company, Princeton, NJ (US)
Filed on Apr. 20, 2022, as Appl. No. 17/725,340.
Application 17/725,340 is a continuation of application No. 16/711,105, filed on Dec. 11, 2019, granted, now 11,358,988.
Application 16/711,105 is a continuation of application No. 15/822,744, filed on Nov. 27, 2017, granted, now 10,633,419, issued on Apr. 28, 2020.
Application 15/822,744 is a continuation of application No. 14/938,327, filed on Nov. 11, 2015, granted, now 9,856,292, issued on Jan. 2, 2018.
Claims priority of provisional application 62/204,689, filed on Aug. 13, 2015.
Claims priority of provisional application 62/111,388, filed on Feb. 3, 2015.
Claims priority of provisional application 62/079,944, filed on Nov. 14, 2014.
Prior Publication US 2023/0101323 A1, Mar. 30, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 7/08 (2006.01); A61K 38/00 (2006.01); A61K 38/10 (2006.01); A61K 45/06 (2006.01); A61K 51/08 (2006.01); C07K 7/56 (2006.01)
CPC C07K 7/08 (2013.01) [A61K 38/10 (2013.01); A61K 45/06 (2013.01); A61K 51/088 (2013.01); C07K 7/56 (2013.01); A61K 38/00 (2013.01); Y02A 50/30 (2018.01)] 6 Claims
 
1. A method of enhancing, stimulating, and/or increasing an immune response in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of formula (I)

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
A is

OG Complex Work Unit Chemistry
wherein:
custom character denotes the point of attachment to the carbonyl group and custom character denotes the point of attachment to the nitrogen atom;
m is 1;
w is 0;
R14 and R15 are hydrogen;
R16a is hydrogen;
R16 is —(C(R17a)2)2-X-R30,
X is a chain of between 8 and 46 atoms wherein the atoms are selected from carbon and oxygen and wherein the chain may contain one, two, or three C(O)NH groups embedded therein;
and wherein the chain is optionally substituted with one or two groups independently selected from —CO2H, —C(O)NH2, —CH2C(O)NH2, and —CH2CO2H;
R30 is selected from —CO2H, —C(O)NRwRx, and —CH3 wherein Rw and Rx are hydrogen, provided that when X is all carbon, R30 is other than —CH3;
each R17a is hydrogen,
each of Rc, Rf, Rh, Ri, Rm, and Rn is hydrogen;
Ra, Re, Rj, and Rk, are each independently selected from hydrogen and methyl;
R1 is methyl;
R1 is phenylC1-C3alkyl wherein the phenyl part is optionally substituted with hydroxyl, halo, or methoxy;
R2 is C1-C7alkyl and Rb is methyl; or, R2 and Rb, together with the atoms to which they are attached, form a piperidine ring;
R3 is NRxRy(C1-C7alkyl), NRuRvcarbonylC1-C3alkyl, or carboxyC1-C3alkyl;
R4 and Rd, together with the atoms to which they are attached, form a pyrrolidine ring;
R5 is hydroxyC1-C3alkyl, imidazolylC1-C3alkyl, or NRxRy(C1-C7alkyl);
R6 is carboxyC1-C3alkyl, NRuRvcarbonylC1-C3alkyl, NRxRy(C1-C7alkyl), or C1-C7alkyl;
R7 and Rg, together with the atoms to which they are attached, form a pyrrolidine ring optionally substituted with hydroxy;
R8 and R10 are benzothienyl or indolylC1-C3alkyl optionally substituted with carboxyC1-C3alkyl;
R9 is hydroxyC1-C3alkyl, aminoC1-C3alkyl, or C1-C7alkyl;
R11 is C1-C3alkoxyC1-C3alkyl or C1-C7alkyl;
R12 is C1-C7alkyl or hydroxyC1-C3alkyl; and
R13 is C1-C7 alkyl, carboxyC1-C3alkyl, or —(CH2)3NHC(NH)NH2.