US 9,809,625 B2
Immunomodulators
Kenneth M. Boy, Durham, CT (US); and Paul Michael Scola, Glastonbury, CT (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Filed by BRISTOL-MYERS SQUIBB COMPANY, Princeton, NJ (US)
Filed on Mar. 14, 2016, as Appl. No. 15/68,993.
Claims priority of provisional application 62/134,686, filed on Mar. 18, 2015.
Prior Publication US 2016/0272680 A1, Sep. 22, 2016
Int. Cl. C07K 7/64 (2006.01); C07K 7/08 (2006.01); A61K 39/00 (2006.01); A61K 45/06 (2006.01)
CPC C07K 7/64 (2013.01) [A61K 39/0005 (2013.01); A61K 45/06 (2013.01); C07K 7/08 (2013.01)] 2 Claims
 
1. A compound of formula (I)

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

OG Complex Work Unit Drawing
wherein:
denotes the point of attachment to the carbonyl group and denotes the point of attachment to the nitrogen atom;
m is 1;
w is 0
R14 and R15 are hydrogen;
R16a is selected from hydrogen and C1-C6 alkyl;
R16 is
—(C(R17a)2)—C(O)—NR50R51;
wherein:
each R17a is independently selected from hydrogen and C1-C6alkyl;
one of R50 and R51 is selected from hydrogen and C1-C6alkyl and the other is selected from —(CH2)n′X, C1-C6alkyl, C3-C7cycloalkyl, heterocyclyl, and phenyl, wherein the cycloalkyl is optionally substituted with one, two, or three groups independently selected from C1-C3alkoxy, C1-C3alkyl, amino, cyano, and hydroxy, or;
R50 and R51, together with the nitrogen atom to which they are attached, form a four-, five- six- or seven-membered saturated or unsaturated ring optionally containing one or two additional heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein said ring is optionally substituted with one, two, or three groups selected from C1-C6alkoxy, C1-C3alkyl, cyano, halo, haloC1-C3alkyl, hydroxy, hydroxy(C1-C3alkyl), —NR70R71, oxo, and phenyl; wherein the phenyl is further optionally substituted with one, two, or three groups independently selected from C1-C3alkoxy, cyano, and halo;
n′ is 1-5;
X is selected from —C≡CH,

OG Complex Work Unit Drawing
C2-C6alkoxymethyl, C1-C6alkoxycarbonylmethyl, C1-C6alkylsulfanylmethyl, C1-C6alkylsulfonylmethyl, azidomethyl, tert-butoxymethyl, C3-C7cycloalkyl, haloalkoxymethyl, halomethyl, heterocyclyl, hydroxymethyl, isopropoxymethyl, (NR70R71)methyl, phenyl, phenoxymethyl, and phenylsulfanylmethyl,
one of R70 and R71 is selected from hydrogen, C1-C6alkyl, and hydroxyC2-C6alkyl and the other is selected from C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl, C1-C6alkylsulfonyl, and hydroxyC2-C6alkyl;
Rc, Rf, Rh, Ri, Rm, and Rn are hydrogen;
Ra, Re, and Rj are hydrogen;
Rb, Rk, and Rl are methyl;
R1 is phenylmethyl wherein the phenyl is substituted with hydroxy;
R2 is methyl;
R3 is selected from —CH2C(O)NH2 and —CH2CO2H;
R5 is selected from —CH2NH2, —CH2OH, and —CH2C(O)NH2;
R6 is selected from —CH2CH(CH3)2, —(CH2)2CO2H, and (CH2)2C(O)NH2;
R8 and R10 are —CH2(indolyl), wherein the indolyl is optionally substituted with —CH2CO2H;
R9 is selected from hydrogen, —(CH2)2NH2, CH2OH, and —CH2C(O)NH2;
R11 and R12 are —(CH2)3CH3;
R13 is selected from methyl, —CH2CH(CH3)2, and —(CH2)2CO2H;
Rd and R4, together with the atoms to which they are attached, form a pyrollidine ring; and
Rg and R7, together with the atoms to which they are attached, form a pyrollidine ring, wherein said ring is optionally substituted with one hydroxy group.