Immunomodulator compounds and methods of use

Abstract

Compositions and methods for inducing PD-L1 internalization are disclosed. The methods include reducing the amount of cell surface PD-L1 by contacting a cell expressing PD-L1 with a compound that binds to cell surface PD-L1 and induces PD-L1 internalization. Compounds that induce PD-L1 internalization can be used to enhance, stimulate and/or increase an immune response and treat a PD-1-related disease or condition.

What is claimed is: 
     
         1 . A method of treating a PD-1-related disease or condition in a human subject in need thereof, the method comprising administering to the human subject a therapeutically effective amount of a compound that binds to cell surface PD-L1 and induces PD-L1 internalization. 
     
     
         2 . A method of reducing the amount of cell surface PD-L1, the method comprising contacting a cell expressing PD-L1 with an effective amount of a compound that binds to cell surface PD-L1 and induces PD-L1 internalization. 
     
     
         3 . A method of decreasing or reducing the interaction of PD-1 and PD-L1, the method comprising contacting a cell expressing PD-L1 with an effective amount of a compound that binds to cell surface PD-L1 and induces PD-L1 internalization. 
     
     
         4 . The method of  claim 2 , wherein the cell is an immune cell or a tumor cell. 
     
     
         5 . The method of  claim 4 , wherein the immune cell is a monocyte or macrophage. 
     
     
         6 . A method of enhancing, stimulating and/or increasing an immune response in a human subject in need thereof, the method comprising administering to the human subject a therapeutically effective amount of a compound that binds to cell surface PD-L1 and induces PD-L1 internalization. 
     
     
         7 . The method of  claim 6 , wherein the immune response is a T cell immune response. 
     
     
         8 . The method of  claim 7 , wherein the T cell immune response is a cytotoxic or effector T cell response. 
     
     
         9 . The method of  claim 1 , wherein the PD-1-related disease or condition is a cancer. 
     
     
         10 . The method of  claim 9 , wherein the cancer is melanoma, renal cancer, prostate cancer, breast cancer, colon cancer, lung cancer, squamous cell cancer, head and neck cancer, urothelial cancer, or a cancer with high microsatellite instability (MSI high ). 
     
     
         11 . The method of  claim 1 , wherein the PD-1-related disease or condition is sepsis. 
     
     
         12 . The method of  claim 1 , wherein the PD-1-related disease or condition is a viral, bacterial, fungal, or parasitic infection. 
     
     
         13 . The method of  claim 1 , wherein the compound induces PD-L1 internalization with an IC 50  of 500 nM or lower. 
     
     
         14 . The method of  claim 1 , wherein the compound induces PD-L1 internalization with an IC 50  of 100 nM or lower. 
     
     
         15 . The method of  claim 1 , wherein the compound induces PD-L1 internalization with an IC 50  of 50 nM or lower. 
     
     
         16 . The method of  claim 1 , wherein the compound induces PD-L1 dimerization, and wherein the dimerization occurs prior to PD-L1 internalization. 
     
     
         17 . The method of  claim 16 , wherein the compound induces PD-L1 dimerization with a score in the range of 2.0 to 2.2 in a PD-L1 homogeneous time-resolved fluorescence dimerization assay. 
     
     
         18 . The method of  claim 1 , wherein the compound inhibits binding between PD-L1 and PD-1. 
     
     
         19 . The method of  claim 18 , wherein the compound inhibits binding between PD-L1 and PD-1 with an IC 50  of less than 1 nM. 
     
     
         20 . The method of  claim 1 , comprising administering a second therapeutic agent in combination with the compound. 
     
     
         21 . The method of  claim 20 , wherein the second therapeutic agent is a chemotherapeutic, an immunomodulatory agent, or a kinase inhibitor. 
     
     
         22 . A method for assessing the ability of a compound to induce internalization of PD-L1 in a cell, the method comprising:
 contacting a cell expressing PD-L1 with a compound; and   determining the amount of PD-L1 internalized in the cell in the presence of the compound as compared to the absence of the compound.   
     
     
         23 . A method for assessing the ability of a compound to induce internalization of PD-L1 in a cell, the method comprising:
 identifying a compound that binds to PD-L1;   contacting a cell with the compound; and   determining the amount of PD-L1 internalized in the cell in the presence of the compound as compared to the absence of the compound.   
     
     
         24 . The method of  claim 22 , wherein the ability of the compound to induce internalization of cell surface PD-L1 is measured by contacting a PD-L1-expressing cell with the compound and detecting the amount of PD-L1 internalized in the cell after incubation of the cell with the compound. 
     
     
         25 . The method of  claim 22 , wherein the ability of the compound to induce internalization of cell surface PD-L1 is measured by contacting a PD-L1-expressing cell with the compound and detecting the amount of PD-L1 remaining on the surface of the cell after incubation of the cell with the compound. 
     
     
         26 . The method of  claim 22 , wherein the compound induces PD-L1 internalization with an IC 50  of 500 nM or lower. 
     
     
         27 . The method of  claim 22 , wherein the compound induces PD-L1 internalization with an IC 50  of 100 nM or lower. 
     
     
         28 . The method of  claim 22 , wherein the compound induces PD-L1 internalization with an IC 50  of 50 nM or lower. 
     
     
         29 . The method of  claim 22 , further comprising formulating the compound into a sterile pharmaceutical composition suitable for administration to a human subject. 
     
     
         30 . The method of  claim 29 , wherein the pharmaceutical composition is a tablet, pill, capsule, or intravenous formulation. 
     
     
         31 . The method of  claim 29 , wherein the pharmaceutical composition is suitable for oral, intravenous, subcutaneous administration. 
     
     
         32 . A method for assessing the ability of a compound to induce dimerization and internalization of PD-L1 in a cell, the method comprising:
 measuring the ability of a compound to induce dimerization of PD-L;   contacting a cell expressing PD-L1 with the compound; and   determining the amount of PD-L1 internalized in the cell in the presence of the compound as compared to the absence of the compound.   
     
     
         33 . A method for assessing the ability of a compound to induce dimerization and internalization of PD L1 in a cell, the method comprising:
 identifying a compound that binds to PD-L1;   measuring the ability of the compound to induce dimerization of PD-L1;   contacting a cell expressing PD-L1 with the compound; and   
       determining the amount of PD-L1 internalized in the cell in the presence of the compound as compared to the absence of the compound. 
     
     
         34 . The method of  claim 32 , wherein the compound induces dimerization of PD-L1 with a score between 1.75 and 2.29 in a homogeneous time-resolved fluorescence PD-L1 dimerization assay. 
     
     
         35 . The method of  claim 32 , wherein the compound induces dimerization of PD-L1 with a score between 2.0 and 2.2 in a homogeneous time-resolved fluorescence PD-L1 dimerization assay. 
     
     
         36 . The method of  claim 1 , wherein the compound is a small molecule. 
     
     
         37 . The method of  claim 36 , wherein the compound has a molecular weight of less than 1000 daltons. 
     
     
         38 . The method of  claim 36 , wherein the compound has a molecular weight between 300 and 700 daltons. 
     
     
         39 . A compound of Formula (IV): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein:
 ring A is 5- to 14-membered heteroaryl, 4- to 14-membered heterocycloalkyl, C 6-10  aryl or C 3-10  cycloalkyl, wherein the 5- to 14-membered heteroaryl and 4- to 14-membered heterocycloalkyl each has 1-4 heteroatoms as ring members selected from B, P, N, O and S, wherein the N, P or S atom as ring members is optionally oxidized and one or more carbon atoms as ring members are each optionally replaced by a carbonyl group; and wherein ring A is optionally substituted with 1, 2, 3, 4 or 5 R 20  substituents; 
 L is a bond, —NH—, —O—, —C(O)NH—, —C(═S)NH—, —C(═NH)NH—, —C(═NOH)NH—, —C(═NCN)NH—, —CH 2 O— or —OCH 2 —, wherein the carbonyl group in the —C(O)NH— linkage is attached to ring A; 
 R 21  and R 22  are each independently halo, C 1-6  alkyl or CN; 
 R 23  is H, C 1-6  alkyl or C 1-6  haloalkyl; 
 R 25  is C 1-4  alkyl, C 1-4  alkoxy, C 1-4  haloalkyl, C 1-4  haloalkoxy, CN, halo, OH, —COOH, NH 2 , —NHC 1-4  alkyl or —N(C 1-4  alkyl) 2 ; 
 R 26  is C 1-4  alkyl, C 1-4  alkoxy, C 1-4  haloalkyl, C 1-4  haloalkoxy, CN, halo, OH, —COOH, NH 2 , —NHC 1-4  alkyl or —N(C 1-4  alkyl) 2 ; 
 R 24  is selected from H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, C 6-10  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-14  cycloalkyl-C 1-4  alkyl-, (5-14 membered heteroaryl)-C 1-4  alkyl-, (4-14 membered heterocycloalkyl)-C 1-4  alkyl-, C(O)R a , C(O)NR a R a , C(O)OR a , C(═NR a )R a , C(═NOH)R a , C(═NOH)NR a , C(═NCN)NR a R a , C(═NR a )NR a R a , S(O)R a , S(O)NR a R a , S(O) 2 R a , —P(O)R a R a , —P(O)(OR a )(OR a ), —B(OH) 2 , —B(OR a ) 2  and S(O) 2 NR a R a , wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-14  cycloalkyl-C 1-4  alkyl-, (5-14 membered heteroaryl)-C 1-4  alkyl- and (4-14 membered heterocycloalkyl)-C 1-4  alkyl- of R 24  are each optionally substituted with 1, 2, 3, 4 or 5 independently selected R b  substituents; 
 R 20  is each independently selected from H, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, C 6-10  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-14  cycloalkyl-C 1-4  alkyl-, (5-14 membered heteroaryl)-C 1-4  alkyl-, (4-14 membered heterocycloalkyl)-C 1-4  alkyl-, CN, NO 2 , OR a1 , SR a1 , NHOR a1 , C(O)R a1 , C(O)NR a1 R a1 , C(O)OR a1 , C(O)NR a1 S(O) 2 R a1 , OC(O)R a1 , OC(O)NR a1 R a1 , NHR a1 , NR a1 R a1 , NR a1 C(O)R a1  NR a1 C(═NR a1 )R a1 , NR a1 C(O)OR a1 , NR a1 C(O)NR a1 R a1 , C(═NR a1 )R a1 , C(═NOH)R a1 , C(═NOH)NR a1 , C(═NCN)NR a1 R a1 , NR a1 C(═NCN)NR a1 R a1 , C(═NR a1 )NR a1 R a1 , NR a1 C(═NR a1 )NR a1 R a1  NR a1 S(O)R a1 , NR a1 S(O) 2 R a1 , NR a1 S(O) 2 NR a1 R a1 , S(O)R a1 , S(O)NR a1 R a1 , S(O) 2 R a1 , S(O) 2 NR a1 C(O)R a1 , —P(O)R a1 R a1 , —P(O)(OR a1 )(OR a1 ), —B(OH) 2 , —B(OR a1 ) 2  and S(O) 2 NR a1 R a1 , wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-14  cycloalkyl-C 1-4  alkyl-, (5-14 membered heteroaryl)-C 1-4  alkyl- and (4-14 membered heterocycloalkyl)-C 1-4  alkyl- of R 20  are each optionally substituted with 1, 2, 3, 4 or 5 independently selected R b  substituents; 
 R 27  is each independently selected from H, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, C 6-10  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-14  cycloalkyl-C 1-4  alkyl-, (5-14 membered heteroaryl)-C 1-4  alkyl-, (4-14 membered heterocycloalkyl)-C 1-4  alkyl-, CN, NO 2 , OR a2 , SR a2  NHOR a2 , C(O)R a2 , C(O)NR a2 R a2 , C(O)OR a2 , C(O)NR a2 S(O) 2 R a2 , OC(O)R a2 , OC(O)NR a2 R a2  NHR a2 , NR a2 R a2 , NR a2 C(O)R a2  NR a2 C(═NR a2 )R a2 , NR a2 C(O)OR a2 , NR a2 C(O)NR a2 R a2 , C(═NR a2 )R a2 , C(═NOH)R a2 , C(═NOH)NR a2 , C(═NCN)NR a2 R a2  NR a2 C(═NCN)NR a2 R a2 , C(═NR a2 )NR a2 R a2 , NR a2 C(═NR a2 )NR a2 R a2  NR a2 S(O)R a2 , NR a2 S(O) 2 R a2 , NR a2 S(O) 2 NR a2 R a2  S(O)R a2 , S(O)NR a2 R a2 , S(O) 2 R a2 , S(O) 2 NR a2 C(O)R a2 , —P(O)R a2 R a2 , —P(O)(OR a2 )(OR a2 ), —B(OH) 2 , —B(OR a2 ) 2  and S(O) 2 NR a2 R a2 , wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-14  cycloalkyl-C 1-4  alkyl-, (5-14 membered heteroaryl)-C 1-4  alkyl- and (4-14 membered heterocycloalkyl)-C 1-4  alkyl- of R 27  are each optionally substituted with 1, 2, 3, 4 or 5 independently selected R b  substituents; 
 or two R 20  substituents attached to the same ring carbon atom taken together with the ring carbon atom to which they are attached form spiro C 3-6  cycloalkyl or spiro 4- to 7-membered heterocycloalkyl, each of which is optionally substituted with 1, 2, or 3 independently selected R f  substituents; 
 or two R 27  substituents attached to the same ring carbon atom taken together with the ring carbon atom to which they are attached form spiro C 3-6  cycloalkyl or spiro 4- to 7-membered heterocycloalkyl, each of which is optionally substituted with 1, 2, or 3 independently selected R f  substituents; 
 each of R a , R a1  and R a2  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-14  cycloalkyl-C 1-4  alkyl-, (5-14 membered heteroaryl)-C 1-4  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-4  alkyl-, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-14  cycloalkyl-C 1-4  alkyl-, (5-14 membered heteroaryl)-C 1-4  alkyl- and (4-14 membered heterocycloalkyl)-C 1-4  alkyl- of R a , R a1  and R a2  are each optionally substituted with 1, 2, 3, 4, or 5 independently selected R d  substituents; 
 each R d  is independently selected from C 1-6  alkyl, C 1-6  haloalkyl, halo, C 6-10  aryl, 5-14 membered heteroaryl, C 3-14  cycloalkyl, 4-14 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-14  cycloalkyl-C 1-4  alkyl-, (5-14 membered heteroaryl)-C 1-4  alkyl-, (4-14 membered heterocycloalkyl)-C 1-4  alkyl-, CN, NH 2 , NHOR e , OR e , SR e , C(O)R e , C(O)NR e R e , C(O)OR e , C(O)NR e S(O) 2 R e , OC(O)R e , OC(O)NR e R e , NHR e , NR e R e , NR e C(O)R e , NR e C(═NR e )R e , NR e C(O)NR e R e , NR e C(O)OR e , C(═NR e )NR e R e , NR e C(═NR e )NR e R e , NR e C(═NOH)NR e R e , NR e C(═NCN)NR e R e , S(O)R e , S(O)NR e R e , S(O) 2 R e , S(O) 2 NR e C(O)R e , NR e S(O) 2 R e , NR e S(O) 2 NR e R e , —P(O)R e R e , —P(O)(OR e )(OR e ), —B(OH) 2 , —B(OR e ) 2  and S(O) 2 NR e R e , wherein the C 1-6  alkyl, C 1-6  haloalkyl, C 6-10  aryl, 5-14 membered heteroaryl, C 3-14  cycloalkyl, 4-14 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-14  cycloalkyl-C 1-4  alkyl-, (5-14 membered heteroaryl)-C 1-4  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-4  alkyl- of R d  are each optionally substituted with 1, 2, or 3 independently selected R f  substituents; 
 each R e  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-10  cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-10  cycloalkyl-C 1-4  alkyl-, (5-10 membered heteroaryl)-C 1-4  alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4  alkyl-, wherein the C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-10  cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-10  cycloalkyl-C 1-4  alkyl-, (5-10 membered heteroaryl)-C 1-4  alkyl- and (4-10 membered heterocycloalkyl)-C 1-4  alkyl- of R e  are each optionally substituted with 1, 2 or 3 independently selected R f  substituents; 
 each R b  substituent is independently selected from halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, C 6-10  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-14  cycloalkyl-C 1-4  alkyl-, (5-14 membered heteroaryl)-C 1-4  alkyl-, (4-14 membered heterocycloalkyl)-C 1-4  alkyl-, CN, OH, NH 2 , NO 2 , NHOR c , OR c , SR c , C(O)R c , C(O)NR c R c , C(O)OR c , C(O)NR c S(O) 2 R c , OC(O)R c , OC(O)NR c R c , C(═NOH)R c , C(═NOH)NR c , C(═NCN)NR c R c , NR c C(═NCN)NR c R c , C(═NR c )NR c R c , NR c C(═NR c )NR c R c , NHR c , NR c R c , NR c C(O)R c , NR c C(═NR c )R c , NR c C(O)OR c , NR c C(O)NR c R c , NR c S(O)R c , NR c S(O) 2 R c , NR c S(O) 2 NR c R c , S(O)R c , S(O)NR c R c , S(O) 2 R c , S(O) 2 NR c C(O)R c , —P(O)R c R c , —P(O)(OR c )(OR c ), —B(OH) 2 , —B(OR c ) 2  and S(O) 2 NR c R c ; wherein the C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-14  cycloalkyl-C 1-4  alkyl-, (5-14 membered heteroaryl)-C 1-4  alkyl- and (4-14 membered heterocycloalkyl)-C 1-4  alkyl- of R b  are each further optionally substituted with 1, 2 or 3 independently selected R d  substituents; 
 each R c  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-14  cycloalkyl-C 1-4  alkyl-, (5-14 membered heteroaryl)-C 1-4  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-4  alkyl-, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-14  cycloalkyl-C 1-4  alkyl-, (5-14 membered heteroaryl)-C 1-4  alkyl- and (4-14 membered heterocycloalkyl)-C 1-4  alkyl- of R c  are each optionally substituted with 1, 2, 3, 4, or 5 independently selected R f  substituents; 
 each R f  is independently selected from C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-10  cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-10  cycloalkyl-C 1-4  alkyl-, (5-10 membered heteroaryl)-C 1-4  alkyl-, (4-10 membered heterocycloalkyl)-C 1-4  alkyl-, halo, CN, NHOR g , OR g , SR g , C(O)R g , C(O)NR g R g , C(O)OR g , C(O)NR g S(O) 2 R g , OC(O)R g , OC(O)NR g R g , NHR g , NR g R g , NR g C(O)R g , NR g C(═NR g )R g , NR g C(O)NR g R g , NR g C(O)OR g , C(═NR g )NR g R g , NR g C(═NR g )NR g R g , S(O)R g , S(O)NR g R g , S(O) 2 R g , S(O) 2 NR g C(O)R g , NR g S(O) 2 R g , NR g S(O) 2 NR g R g , —P(O)R g R g , —P(O)(OR g )(OR g ), —B(OH) 2 , —B(OR g ) 2  and S(O) 2 NR g R g ; wherein the C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-10  cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-10  cycloalkyl-C 1-4  alkyl-, (5-10 membered heteroaryl)-C 1-4  alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4  alkyl- of R f  are each optionally substituted with 1, 2, 3, 4, or 5 independently selected R n  substituents; 
 each R n  is substituents independently selected from C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-10  cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-10  cycloalkyl-C 1-4  alkyl-, (5-10 membered heteroaryl)-C 1-4  alkyl-, (4-10 membered heterocycloalkyl)-C 1-4  alkyl-, halo, CN, NHOR o , OR o , SR o , C(O)R o , C(O)NR o R o , C(O)OR o , C(O)NR o S(O) 2 R o , OC(O)R o , OC(O)NR o R o , NHR o , NR o R o , NR o C(O)R o , NR o C(═NR o )R o , NR o C(O)NR o R o , NR o C(O)OR o , C(═NR o )NR o R o , NR o C(═NR o )NR o R o , S(O)R o , S(O)NR o R o , S(O) 2 R o , S(O) 2 NR o C(O)R o , NR o S(O) 2 R o , NR o S(O) 2 NR o R o , —P(O)R o R o , —P(O)(OR o )(OR o ), —B(OH) 2 , —B(OR o ) 2  and S(O) 2 NR o R o , wherein the C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-10  cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-10  cycloalkyl-C 1-4  alkyl-, (5-10 membered heteroaryl)-C 1-4  alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4  alkyl- of R 15  are each optionally substituted with 1, 2 or 3 independently selected R q  substituents; 
 each R g  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-10  cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-10  cycloalkyl-C 1-4  alkyl-, (5-10 membered heteroaryl)-C 1-4  alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4  alkyl-, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-10  cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-10  cycloalkyl-C 1-4  alkyl-, (5-10 membered heteroaryl)-C 1-4  alkyl- and (4-10 membered heterocycloalkyl)-C 1-4  alkyl- of R g  are each optionally substituted with 1, 2, or 3 independently selected R p  substituents; 
 each R p  is independently selected from C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-10  cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-10  cycloalkyl-C 1-4  alkyl-, (5-10 membered heteroaryl)-C 1-4  alkyl-, (4-10 membered heterocycloalkyl)-C 1-4  alkyl-, halo, CN, NHOR r , OR r , SR r , C(O)R r , C(O)NR r R r , C(O)OR r , C(O)NR r S(O) 2 R r , OC(O)R r , OC(O)NR r R r , NHR r , NR r R r , NR r C(O)R r , NR r C(═NR r )R r  NR r C(O)NR r R r , NR r C(O)OR r , C(═NR r ) NR r C(═NR r )NR r R r , NR r C(═NOH)NR r R r , NR r C(═NCN)NR r R r , S(O)R r , S(O)NR r R r , S(O) 2 R r , S(O) 2 NR r C(O)R r , NR r S(O) 2 R r , NR r S(O) 2 NR r R r , —P(O)R r R r , —P(O)(OR r )(OR r ), —B(OH) 2 , —B(OR r ) 2  and S(O) 2 NR r R r , wherein the C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, C 3-10  cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10  aryl-C 1-4  alkyl-, C 3-10  cycloalkyl-C 1-4  alkyl-, (5-10 membered heteroaryl)-C 1-4  alkyl- and (4-10 membered heterocycloalkyl)-C 1-4  alkyl- of R p  is optionally substituted with 1, 2 or 3 independently selected R q  substituents; 
 or any two R a  substituents together with the boron, phosphorus or nitrogen atom to which they are attached form a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 independently selected R h  substituents; 
 or any two R a1  substituents together with the boron, phosphorus or nitrogen atom to which they are attached form a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 independently selected R h  substituents; 
 or any two R a2  substituents together with the boron, phosphorus or nitrogen atom to which they are attached form a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 independently selected R h  substituents; 
 each R h  is independently selected from C 1-6  alkyl, C 3-10  cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10  aryl, 5-10 membered heteroaryl, C 6-10  aryl-C 1-4  alkyl-, C 3-10  cycloalkyl-C 1-4  alkyl-, (5-10 membered heteroaryl)-C 1-4  alkyl-, (4-10 membered heterocycloalkyl)-C 1-4  alkyl-, C 1-6  haloalkyl, C 1-6  haloalkoxy, C 2-6  alkenyl, C 2-6  alkynyl, halo, CN, OR i , SR i , NHOR i , C(O)R i , C(O)NR i R i , C(O)OR i , C(O)NR i S(O) 2 R i , OC(O)R i , OC(O)NR i R i , NHR i , NR i R i , NR i C(O)R i , NR i C(═NR i )R i , NR i C(O)NR i R i , NR i C(O)OR i , C(═NR i )NR i R i , NR i C(═NR i )NR i R i , S(O)R i , S(O)NR i R i , S(O) 2 R i , S(O) 2 NR i C(O)R i , NR i S(O) 2 R i , NR i S(O) 2 NR i R i , —P(O)R i R i , —P(O)(OR i )(OR i ), —B(OH) 2 , —B(OR i ) 2  and S(O) 2 NR i R i , wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10  aryl, 5-10 membered heteroaryl, C 6-10  aryl-C 1-4  alkyl-, C 3-10  cycloalkyl-C 1-4  alkyl-, (5-10 membered heteroaryl)-C 1-4  alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4  alkyl- of R h  are each optionally substituted by 1, 2, or 3 independently selected R substituents; 
 each R j  is independently selected from C 3-6  cycloalkyl, C 6-10  aryl, 5 or 6-membered heteroaryl, 4-7 membered heterocycloalkyl, C 2-4  alkenyl, C 2-4  alkynyl, halo, C 1-4  alkyl, C 1-4  haloalkyl, C 1-4  haloalkoxy, CN, NHOR k , OR k , SR k , C(O)R k , C(O)NR k R k , C(O)OR k , C(O)NR k S(O) 2 R k , OC(O)R k , OC(O)NR k R k , NHR k , NR k R k , NR k C(O)R k , NR k C(═NR k )R k , NR k C(O)NR k R k , NR k C(O)OR k , C(═NR k )NR k R k , NR k C(═NR k )NR k R k , S(O)R k , S(O)NR k R k , S(O) 2 R k , S(O) 2 NR k C(O)R k , NR k S(O) 2 R k , NR k S(O) 2 NR k R k , —P(O)R k R k , —P(O)(OR k )(OR k ), —B(OH) 2 , —B(OR) 2  and S(O) 2 NR k R k , wherein the C 1-4  alkyl, C 3-6  cycloalkyl, C 6-10  aryl, 5- or 6-membered heteroaryl, 4-7 membered heterocycloalkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, and C 1-4  haloalkoxy of R j  are each optionally substituted with 1, 2 or 3 independently selected R q  substituents; 
 or two R h  groups attached to the same carbon atom of the 4- to 10-membered heterocycloalkyl taken together with the carbon atom to which they are attached form a C 3-6  cycloalkyl or 4- to 6-membered heterocycloalkyl having 1-2 heteroatoms as ring members selected from O, N or S; 
 or any two R c  substituents together with the boron, phosphorus or nitrogen atom to which they are attached form a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h  substituents; 
 or any two R e  substituents together with the boron, phosphorus or nitrogen atom to which they are attached form a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h  substituents; 
 or any two R g  substituents together with the boron, phosphorus or nitrogen atom to which they are attached form a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h  substituents; 
 or any two R i  substituents together with the boron, phosphorus or nitrogen atom to which they are attached form a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R q  substituents; 
 or any two R k  substituents together with the boron, phosphorus or nitrogen atom to which they are attached form a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R q  substituents; 
 or any two R o  substituents together with the boron, phosphorus or nitrogen atom to which they are attached form a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h  substituents; 
 or any two R r r substituents together with the boron, phosphorus or nitrogen atom to which they are attached form a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h  substituents; 
 each R i , R k , R o  or R r  is independently selected from H, C 1-4  alkyl, C 3-6  cycloalkyl, C 6-10  aryl, 5 or 6-membered heteroaryl, 4-7 membered heterocycloalkyl, C 1-4  haloalkyl, C 1-4  haloalkoxy, C 2-4  alkenyl, and C 2-4  alkynyl, wherein the C 1-4  alkyl, C 3-6  cycloalkyl, C 6-10  aryl, 5 or 6-membered heteroaryl, 4-7 membered heterocycloalkyl, C 2-4  alkenyl, and C 2-4  alkynyl of R i , R k , R o  or R r  are each optionally substituted with 1, 2 or 3 independently selected R q  substituents; 
 each R q  is independently selected from halo, OH, CN, —COOH, B(OH) 2 , NH 2 , —NH—C 1-6  alkyl, —N(C 1-6  alky) 2 , C 1-6  alkyl, C 1-6  alkoxy, C 1-6  alkylthio, C 1-6  haloalkyl, C 1-6  haloalkoxy, phenyl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl and C 3-6  cycloalkyl, wherein the C 1-6  alkyl, phenyl, C 3-6  cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl of R q  are each optionally substituted with 1, 2 or 3 substituents independently selected from halo, OH, CN, —COOH, NH 2 , C 1-4  alkyl, C 1-4  alkoxy, C 1-4  haloalkyl, C 1-4  haloalkoxy, phenyl, C 3-10  cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl; 
 the subscript m is an integer of 0, 1, 2 or 3; 
 the subscript n is an integer of 0, 1, 2 or 3; 
 the subscript p is an integer of 1, 2, 3, 4, 5 or 6; and 
    is a single bond or a double bond to maintain the 5-membered imidazole ring being aromatic. 
 
       
     
     
         40 . The compound of  claim 39 , having Formula (V): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof. 
       
     
     
         41 . The compound of  claim 39 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein (1) when L is a bond, ring A is not 2-benzoxazolyl; (2) when L is a bond, ring A is not [1,2,4]triazolo[1,5-a]pyridin-2-yl; (3) when L is —NH—, ring A is not 1,7-naphthyridin-8-yl or pyrido[3,2-d]pyrimidin-4-yl; or (4) when L is —C(O)NH—, ring A is not 2-pyridyl. 
     
     
         42 . The compound of  claim 39 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein ring A is selected from: 
       
         
           
           
               
               
           
         
       
       where in each subscript q is independently an integer of 1, 2,3 or 4; each R 28  is independently H or C 1-6  alkyl; and the wavy line indicates the point of attachment to L. 
     
     
         43 . The compound of  claim 39 , having Formula (Va): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 28  is H or C 1-6  alkyl and the subscript q is an integer of 1, 2 or 3. 
       
     
     
         44 . The compound of  claim 39 , having Formula (Va-1): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 28  is H or C 1-6  alkyl. 
       
     
     
         45 . The compound of  claim 39 , having Formula (Vb): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the subscript q is an integer of 1, 2 or 3. 
       
     
     
         46 . The compound of  claim 39 , having Formula (Vb-1): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the subscript q is an integer of 1, 2 or 3. 
       
     
     
         47 . The compound of  claim 39 , having Formula (Vc): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the subscript q is an integer of 1, 2 or 3. 
       
     
     
         48 . The compound of  claim 39 , having Formula (Vc-1): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the subscript q is an integer of 1, 2 or 3. 
       
     
     
         49 . The compound of  claim 39 , having Formula (Vd): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the subscript q is an integer of 1, 2 or 3. 
       
     
     
         50 . The compound of  claim 39 , having Formula (Vd-1): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the subscript q is an integer of 1, 2 or 3. 
       
     
     
         51 . The compound of  claim 39 , having Formula (Ve): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 28  is H or C 1-6  alkyl and the subscript q is an integer of 1, 2 or 3. 
       
     
     
         52 . The compound of  claim 39 , having Formula (Ve-1): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the subscript q is an integer of 1, 2 or 3. 
       
     
     
         53 . The compound of  claim 39 , having Formula (Vf): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the subscript q is an integer of 1, 2 or 3. 
       
     
     
         54 . The compound of  claim 39 , having Formula (Vf-1): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the subscript q is an integer of 1, 2 or 3. 
       
     
     
         55 . The compound of  claim 39 , having Formula (Vg): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof. 
       
     
     
         56 . The compound of  claim 39 , having Formula (Vg-1): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof. 
       
     
     
         57 . The compound of  claim 39 , having Formula (Vg-2): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof. 
       
     
     
         58 . The compound of  claim 39 , having Formula (Vh): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof. 
       
     
     
         59 . The compound of  claim 39 , having Formula (Vh-1): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof. 
       
     
     
         60 . The compound of  claim 39 , having Formula (Vh-2): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or a stereoisomer thereof. 
       
     
     
         61 . The compound of  claim 39 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 20  is H, C 1-6  alkyl, 2-hydroxypropyl, (R)-2-hydroxypropyl, (S)-2-hydroxypropyl, 2-hydroxyethyl, 1-(methylsulfonyl)piperidin-4-yl, tetrahydro-2H-pyran-4-yl, (tetrahydro-2H-pyran-4-yl)methyl, 1-(hydroxymethyl)cyclopropyl)methyl, (S)-(2,3-dihydroxypropyl)-1-methyl, (2,3-dihydroxypropyl)-1-methyl, (R)-(2,3-dihydroxypropyl)-1-methyl, carboxymethyl, 1-acetylpiperidin-4-yl, 4-carboxy-4-methylcyclohexyl, 3-(methylsulfonamido)propyl, trans-(4-carboxycyclohexyl)methyl, cis-(4-carboxycyclohexyl)methyl, (3-carboxypyrrolidin-1-yl)methyl, (R)-(3-carboxypyrrolidin-1-yl)methyl, (S)-(3-carboxypyrrolidin-1-yl)methyl, (3-hydroxypyrrolidin-1-yl)methyl, (R)-(3-hydroxypyrrolidin-1-yl)methyl, (S)-(3-hydroxypyrrolidin-1-yl)methyl, pyrrolidin-1-ylmethyl, 2-(dimethylamino)acetyl, (5-cyanopyridin-3-yl)methoxy, (2-carboxypiperidin-1-yl)methyl, (R)-(2-carboxypiperidin-1-yl)methyl, (S)-(2-carboxypiperidin-1-yl)methyl, halo, cyclobutyl, cyclopropylmethyl, or CN. 
     
     
         62 . The compound of  claim 39 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 20  is H, C 1-6  alkyl, 2-hydroxypropyl, (R)-2-hydroxypropyl, (S)-2-hydroxypropyl, 2-hydroxyethyl, 1-(methylsulfonyl)piperidin-4-yl, tetrahydro-2H-pyran-4-yl, (tetrahydro-2H-pyran-4-yl)methyl, 1-(hydroxymethyl)cyclopropyl)methyl, (S)-(2,3-dihydroxypropyl)-1-methyl, (2,3-dihydroxypropyl)-1-methyl, (R)-(2,3-dihydroxypropyl)-1-methyl, carboxymethyl, 1-acetylpiperidin-4-yl, 4-carboxy-4-methylcyclohexyl, 3-(methylsulfonamido)propyl, trans-(4-carboxycyclohexyl)methyl, cis-(4-carboxycyclohexyl)methyl, (3-carboxypyrrolidin-1-yl)methyl, (R)-(3-carboxypyrrolidin-1-yl)methyl, (S)-(3-carboxypyrrolidin-1-yl)methyl, (3-hydroxypyrrolidin-1-yl)methyl, (R)-(3-hydroxypyrrolidin-1-yl)methyl, (S)-(3-hydroxypyrrolidin-1-yl)methyl, pyrrolidin-1-ylmethyl, 2-(dimethylamino)acetyl, (5-cyanopyridin-3-yl)methoxy, (2-carboxypiperidin-1-yl)methyl, (R)-(2-carboxypiperidin-1-yl)methyl, (S)-(2-carboxypiperidin-1-yl)methyl, halo, cyclobutyl, cyclopropylmethyl, CN, trans-(4-carboxycyclohexyl)ethyl, cis-(4-carboxycyclohexyl)ethyl, 4-carboxycyclohexyl, trans-4-carboxycyclohexyl, cis-4-carboxycyclohexyl, 4-carboxybenzyl, 4-carboxyphenethyl, 2-(4-carboxy-4-methylcyclohexyl)methyl, 2-(4-carboxy-4-methylcyclohexyl)ethyl, (4-carboxybicyclo[2.2.2]octan-1-yl)methyl, 4-carboxybicyclo[2.2.1]heptan-1-yl, (4-carboxybicyclo[2.2.1]heptan-1-yl)methyl, 4-carboxy-4-methylcyclohexyl, (S)-3-hydroxypyrrolidin-1-yl)acetyl, (R)-3-hydroxypyrrolidin-1-yl)acetyl, 4-carboxy-4-ethylcyclohexyl, N-isopropyl-N-methylglycyl, (R)-3-carboxy-3-methylpyrrolidin-1-yl, (S)-3-carboxy-3-methylpyrrolidin-1-yl, (S)-1-hydroxypropan-2-yl)glycyl, (R)-1-hydroxypropan-2-yl)glycyl, (3-hydroxycyclobutyl)glycyl, cis-(3-hydroxycyclobutyl)glycyl, trans-(3-hydroxycyclobutyl)glycyl, dimethylglycyl, N-ethyl-N-methylglycyl, ethyl(methyl)amino)propanoyl, or 1-carboxyadamant-4-yl. 
     
     
         63 . The compound of  claim 39 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein L is —C(O)NH—. 
     
     
         64 . The compound of  claim 39 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein L is a bond. 
     
     
         65 . The compound of  claim 39 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 21  and R 22  are each independently Cl, CN or methyl. 
     
     
         66 . The compound of  claim 39 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 23  is methyl. 
     
     
         67 . The compound of  claim 39 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 24  is H, C 1-6  alkyl, 2-hydroxypropyl, (R)-2-hydroxypropyl, (S)-2-hydroxypropyl, 2-hydroxyethyl, C 3-6  cycloalkyl, C 3-6  cycloalkyl-C 1-4  alkyl-, 1-(methylsulfonyl)piperidin-4-yl or tetrahydro-2H-pyran-4-yl. 
     
     
         68 . The compound of  claim 39 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 24  is H, C 1-6  alkyl, 2-hydroxypropyl, (R)-2-hydroxypropyl, (S)-2-hydroxypropyl, 2-hydroxyethyl, C 3-6  cycloalkyl, C 3-6  cycloalkyl-C 1-4  alkyl-, 1-(methylsulfonyl)piperidin-4-yl, or tetrahydro-2H-pyran-4-yl, 4-hydroxycyclohexyl, trans-(4-carboxycyclohexyl)methyl, cis-(4-carboxycyclohexyl)methyl, (4-carboxycyclohexyl)ethyl, 4-carboxy-4-methylcyclohexyl, or 2-(4-carboxycyclohexyl)ethyl. 
     
     
         69 . The compound of  claim 42 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the subscript q is 1. 
     
     
         70 . The compound of  claim 39 , wherein the compound is selected from
 N,N′-(2-chloro-2′-cyanobiphenyl-3,3′-diyl)bis(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide);   N-(2-chloro-2′-cyano-3′-(3-methyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide;   N-(2′-chloro-2-cyano-3′-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carboxamido)biphenyl-3-yl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   N-(2′-chloro-2-cyano-3′-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamido)biphenyl-3-yl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   N,N′-(2,2′-dichlorobiphenyl-3,3′-diyl)bis(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide);   N,N′-(2-chloro-2′-methyl-[1,1′-biphenyl]-3,3′-diyl)bis(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide);   N-(2-chloro-2′-cyano-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide;   N,N′-(2-chloro-2′-cyanobiphenyl-3,3′-diyl)bis(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide);   N,N′-(2-chloro-2′-methylbiphenyl-3,3′-diyl)bis(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide);   (S)-N,N′-(2-chloro-2′-methylbiphenyl-3,3′-diyl)bis(5-((S)-2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide);   N,N′-(2-chloro-2′-methylbiphenyl-3,3′-diyl)bis(5-(2-hydroxyethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide);   (S)-N-(2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methylbiphenyl-3-yl)-5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (R)-N-(2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methylbiphenyl-3-yl)-5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (S)-N-(2-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methylbiphenyl-3-yl)-5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (S)-N-(2,2′-dichloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-yl)-5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   N-(2-chloro-2′-methyl-3′-(1-methyl-5-(1-(methylsulfonyl)piperidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-yl)-1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   N-(2-chloro-2′-methyl-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-yl)-1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   N-(2-chloro-2′-methyl-3′-(1-methyl-5-((tetrahydro-2H-pyran-4-yl)methyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-yl)-1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   N-(2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methylbiphenyl-3-yl)-5-((1-(hydroxymethyl)cyclopropyl)methyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (S)-N-(2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methylbiphenyl-3-yl)-5-(2,3-dihydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   2-(2-(2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methylbiphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)acetic acid;   5-(1-acetylpiperidin-4-yl)-N-(2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methylbiphenyl-3-yl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   4-(2-(2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methylbiphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)-1-methylcyclohexanecarboxylic acid;   N-(2-chloro-2′-methyl-3′-(1-methyl-5-(3-(methylsulfonamido)propyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-yl)-1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   Trans-4-((2-(2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methylbiphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)cyclohexane-1-carboxylic acid;   N-(2-chloro-2′-cyano-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-yl)-5-(2-hydroxyethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (S)-N-(2-chloro-2′-cyano-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-yl)-5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (R)-N-(2-chloro-2′-cyano-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-yl)-5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (S)-N-(2′-chloro-2-methyl-3′-(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)-5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (S)-N-(2′-chloro-3′-(5-(2-hydroxyethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methylbiphenyl-3-yl)-5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (S)-N-(2′-chloro-2-methyl-3′-(1-methyl-5-(1-(methylsulfonyl)piperidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-yl)-5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (S)-N-(2-chloro-3′-(5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methylbiphenyl-3-yl)-5-cyclobutyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (S)-N-(2-chloro-3′-(5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methylbiphenyl-3-yl)-5-isopropyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (S)-N-(2-chloro-3′-(5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methylbiphenyl-3-yl)-5-(cyclopropylmethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (S)-N-(2′-chloro-2-methyl-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-yl)-5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (R)-N-(2-chloro-3′-(5-((3-hydroxypyrrolidin-1-yl)methyl)-1-methyl-2-oxo-1,2-dihydropyridine-3-carboxamido)-2′-methylbiphenyl-3-yl)-1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (R)-1-((5-(2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methylbiphenyl-3-ylcarbamoyl)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)methyl)pyrrolidine-3-carboxylic acid;   N-(2-chloro-2′-methyl-3′-(1-methyl-2-oxo-5-(pyrrolidin-1-ylmethyl)-1,2-dihydropyridine-3-carboxamido)biphenyl-3-yl)-1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   N-(2-chloro-3′-(5-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1-methyl-2-oxo-1,2-dihydropyridine-3-carboxamido)-2′-methylbiphenyl-3-yl)-5-((S)-2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (S)-N-(2-chloro-2′-methyl-3′-(1-methyl-2-oxo-5-(pyrrolidin-1-ylmethyl)-1,2-dihydropyridine-3-carboxamido)biphenyl-3-yl)-5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   N-(2-chloro-3′-(5-(2-(dimethylamino)acetyl)-5,6-dihydro-4H-pyrrolo[3,4-d]thiazol-2-yl)-2′-methylbiphenyl-3-yl)-1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   (S)-1-(5-chloro-4-((2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((5-cyanopyridin-3-yl)methoxy)benzyl)piperidine-2-carboxylic acid; and   cis-4-((2-((2-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   or a pharmaceutically acceptable salt or a stereoisomer thereof.   
     
     
         71 . The compound of  claim 39 , wherein the compound is selected from
 trans-4-((2-(2,2′-dichloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)cyclohexane-1-carboxylic acid;   trans-4-((2-(2,2′-dichloro-3′-(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)cyclohexane-1-carboxylic acid;   trans-4-((2-(2,2′-dichloro-3′-(5-ethyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)cyclohexane-1-carboxylic acid;   trans-4-((2-(2,2′-dichloro-3′-(5-(cyclopropylmethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)cyclohexane-1-carboxylic acid;   trans-4-((2-(2,2′-dichloro-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)cyclohexane-1-carboxylic acid;   trans-4-((2-((2,2′-dichloro-3′-(5-(2-hydroxyethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   trans-4-((2-((2,2′-dichloro-3′-(5-((S)-2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   trans-4-((2-((2,2′-dichloro-3′-(5-((R)-2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   cis-4-((2-((2,2′-dichloro-3′-(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   cis-4-((2-((2,2′-dichloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   cis-4-((2-((2,2′-dichloro-3′-(5-ethyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   cis-4-((2-((2,2′-dichloro-3′-(5-(cyclopropylmethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   cis-4-((2-((2,2′-dichloro-3′-(5-isopropyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   cis-4-((2-((2,2′-dichloro-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   cis-4-((2-((2,2′-dichloro-3′-(5-(2-hydroxyethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   cis-4-((2-((2,2′-dichloro-3′-(5-((S)-2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   cis-4-((2-((2,2′-dichloro-3′-(5-((R)-2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   4-(2-(2-((2,2′-dichloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   4-(2-(2-((2,2′-dichloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)benzoic acid;   4-(2-((2,2′-dichloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)cyclohexane-1-carboxylic acid;   4-(2-((2,2′-dichloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-methylcyclohexane-1-carboxylic acid;   4-((2-((2,2′-dichloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)bicyclo[2.2.2]octane-1-carboxylic acid;   4-((2-((2,2′-dichloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)-1-methylcyclohexane-1-carboxylic acid;   4-(2-((2,2′-dichloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-ethylcyclohexane-1-carboxylic acid;   4-((2-((2,2′-dichloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid;   trans-4-(2-(2-((2,2′-dichloro-3′-(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2,2′-dichloro-3′-(5-ethyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2,2′-dichloro-3′-(5-(cyclopropylmethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2,2′-dichloro-3′-(5-isopropyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2,2′-dichloro-3′-(5-cyclobutyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2,2′-dichloro-3′-(5-cyclopentyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2,2′-dichloro-3′-(5-cyclohexyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2,2′-dichloro-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2,2′-dichloro-3′-(5-(2-hydroxyethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2,2′-dichloro-3′-(5-((S)-2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2,2′-dichloro-3′-(5-((R)-2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   4-(2-(2-((2,2′-dichloro-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)benzoic acid;   4-(2-((2,2′-dichloro-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)cyclohexane-1-carboxylic acid;   4-(2-((2,2′-dichloro-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-methylcyclohexane-1-carboxylic acid;   4-(2-((2,2′-dichloro-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-ethylcyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   4-(2-(2-((2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)benzoic acid;   4-((2-((2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid;   4-((2-(2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methylbiphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)bicyclo[2.2.2]octane-1-carboxylic acid;   4-(2-((2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-ethylcyclohexane-1-carboxylic acid;   4-(2-((2′-chloro-3′-(5-ethyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-methylcyclohexane-1-carboxylic acid;   4-(2-((2′-chloro-3′-(5-isopropyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-methylcyclohexane-1-carboxylic acid;   4-(2-((2′-chloro-3′-(5-cyclohexyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-methylcyclohexane-1-carboxylic acid;   4-(2-((2′-chloro-2-methyl-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-methylcyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2′-chloro-2-methyl-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-((2-((2′-chloro-2-methyl-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   4-(2-((2′-chloro-2-methyl-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)cyclohexane-1-carboxylic acid;   4-(2-((2′-chloro-2-methyl-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-ethylcyclohexane-1-carboxylic acid;   cis-4-((2-((2′-chloro-2-methyl-3′-(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   cis-4-((2-((2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-((2-((2-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   4-(2-(2-((2-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)benzoic acid;   4-(2-((2-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-methylcyclohexane-1-carboxylic acid;   4-((2-((2-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid;   4-((2-((2-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)-1-methylcyclohexane-1-carboxylic acid;   4-(2-((2-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-ethylcyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2-chloro-2′-methyl-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-((2-((2-chloro-2′-methyl-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   4-(2-(2-((2-chloro-2′-methyl-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)benzoic acid;   4-(2-((2-chloro-2′-methyl-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2-chloro-2′-methyl-3′-(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2-chloro-3′-(5-ethyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2-chloro-3′-(5-(cyclopropylmethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2-chloro-3′-(5-isopropyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2-chloro-3′-(5-cyclopentyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2-chloro-3′-(5-cyclohexyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2-chloro-3′-(5-(2-hydroxyethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-(2-chloro-3′-(5-((S)-2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methylbiphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)ethyl)cyclohexane-1-carboxylic acid;   Trans-4-(2-(2-(2-chloro-3′-(5-(4-hydroxycyclohexyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methylbiphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)ethyl)cyclohexane-1-carboxylic acid;   cis-4-((2-((2-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   cis-4-((2-((2-chloro-2′-methyl-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   cis-4-((2-((2-chloro-3′-(5-((R)-2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   cis-4-((2-((2-chloro-3′-(5-(4-hydroxycyclohexyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   4-(2-((2-chloro-3′-(5-cyclohexyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-methylcyclohexane-1-carboxylic acid;   (R)-4-(2-((2-chloro-3′-(5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-methylcyclohexane-1-carboxylic acid;   4-(2-((2-chloro-2′-methyl-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-methylcyclohexane-1-carboxylic acid;   (S)-4-(2-((2-chloro-3′-(5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-methylcyclohexane-1-carboxylic acid;   trans-4-((2-((2,2′-dichloro-3′-(5-(4-hydroxycyclohexyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   cis-4-((2-((2,2′-dichloro-3′-(5-(4-hydroxycyclohexyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2,2′-dichloro-3′-(5-(4-hydroxycyclohexyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-((2-((2′-chloro-2-cyano-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2′-chloro-2-cyano-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-((2-((2-chloro-2′-cyano-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-(2-chloro-2′-cyano-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2-chloro-2′-cyano-3′-(5-ethyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2-chloro-2′-cyano-3′-(5-isopropyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2-chloro-2′-cyano-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2′-chloro-2-cyano-3′-(5-ethyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-(2-(2-((2′-chloro-2-cyano-3′-(5-isopropyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-((2-((2′-chloro-2-cyano-3′-(5-ethyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   trans-4-((2-((2′-chloro-2-cyano-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   trans-4-((2-(2-chloro-3′-(5-(2-(isopropyl(methyl)amino)acetyl)-5,6-dihydro-4H-pyrrolo[3,4-d]thiazol-2-yl)-2′-methylbiphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)cyclohexane-1-carboxylic acid;   trans-4-((2-(2-chloro-3′-(5-(2-(ethyl(methyl)amino)acetyl)-5,6-dihydro-4H-pyrrolo[3,4-d]thiazol-2-yl)-2′-methylbiphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)cyclohexane-1-carboxylic acid;   cis-4-((2-(2-chloro-3′-(5-(2-(ethyl(methyl)amino)acetyl)-5,6-dihydro-4H-pyrrolo[3,4-d]thiazol-2-yl)-2′-methylbiphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)cyclohexane-1-carboxylic acid;   4-(2-(2-(2-chloro-3′-(5-(2-(ethyl(methyl)amino)acetyl)-5,6-dihydro-4H-pyrrolo[3,4-d]thiazol-2-yl)-2′-methylbiphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)ethyl)cyclohexane-1-carboxylic acid;   4-(2-(2-(2-chloro-3′-(5-(2-(isopropyl(methyl)amino)acetyl)-5,6-dihydro-4H-pyrrolo[3,4-d]thiazol-2-yl)-2′-methylbiphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)ethyl)cyclohexane-1-carboxylic acid;   (S)-1-(2-(2-(2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methyl-[1,1′-biphenyl]-3-yl)-4,6-dihydro-5H-pyrrolo[3,4-d]oxazol-5-yl)-2-oxoethyl)-3-methylpyrrolidine-3-carboxylic acid;   (S)-N-(2-chloro-3′-(5-((S)-(1-hydroxypropan-2-yl)glycyl)-5,6-dihydro-4H-pyrrolo[3,4-d]oxazol-2-yl)-2′-methyl-[1,1′-biphenyl]-3-yl)-1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   N-(2-chloro-3′-(5-((cis-3-hydroxycyclobutyl)glycyl)-5,6-dihydro-4H-pyrrolo[3,4-d]oxazol-2-yl)-2′-methyl-[1,1′-biphenyl]-3-yl)-1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   N-(2-chloro-3′-(5-((trans-3-hydroxycyclobutyl)glycyl)-5,6-dihydro-4H-pyrrolo[3,4-d]oxazol-2-yl)-2′-methyl-[1,1′-biphenyl]-3-yl)-1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamide;   1-(2-(2-(2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methyl-[1,1′-biphenyl]-3-yl)-4,6-dihydro-5H-pyrrolo[3,4-d]oxazol-5-yl)-2-oxoethyl)piperidine-4-carboxylic acid;   4-(2-((2-chloro-3′-(5-(dimethylglycyl)-5,6-dihydro-4H-pyrrolo[3,4-d]oxazol-2-yl)-2′-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-methylcyclohexane-1-carboxylic acid;   4-(2-(2-((2,2′-dichloro-3′-(5-(N-ethyl-N-methylglycyl)-5,6-dihydro-4H-pyrrolo[3,4-d]oxazol-2-yl)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)cyclohexane-1-carboxylic acid;   4-(2-(2-(2,2′-dichloro-3′-(5-(2-(3-hydroxyazetidin-1-yl)acetyl)-5,6-dihydro-4H-pyrrolo[3,4-d]oxazol-2-yl)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)ethyl)cyclohexane-1-carboxylic acid;   (R)-4-(2-(2-(2,2′-dichloro-3′-(5-(2-(3-hydroxypyrrolidin-1-yl)acetyl)-5,6-dihydro-4H-pyrrolo[3,4-d]oxazol-2-yl)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)ethyl)cyclohexane-1-carboxylic acid;   trans-4-((2-((2,2′-dichloro-3′-(5-(N-ethyl-N-methylglycyl)-5,6-dihydro-4H-pyrrolo[3,4-d]oxazol-2-yl)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)cyclohexane-1-carboxylic acid;   4-(2-((3′-(5-(N-ethyl-N-methylglycyl)-5,6-dihydro-4H-pyrrolo[3,4-d]oxazol-2-yl)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-methylcyclohexane-1-carboxylic acid;   4-(2-((2,2′-dichloro-3′-(5-(3-(ethyl(methyl)amino)propanoyl)-5,6-dihydro-4H-pyrrolo[3,4-d]oxazol-2-yl)-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-1-methylcyclohexane-1-carboxylic acid;   4-(2-((2′-chloro-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methyl-[1,1′-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)adamantane-1-carboxylic acid;   4-((2-(2,2′-dichloro-3′-(5-ethyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid;   4-((2-(2,2′-dichloro-3′-(5-isopropyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid;   4-((2-(2,2′-dichloro-3′-(5-cyclobutyl-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid;   4-((2-(2,2′-dichloro-3′-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid;   4-((2-(2,2′-dichloro-3′-(5-(2-hydroxyethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid;   (S)-4-((2-(2,2′-dichloro-3′-(5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid;   (R)-4-((2-(2,2′-dichloro-3′-(5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid;   4-((2-(2,2′-dichloro-3′-(5-(4-hydroxycyclohexyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)biphenyl-3-ylcarbamoyl)-1-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid; and   (R)-1-((7-chloro-2-(2′-cyano-3′-(1,5-dimethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2-methylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid;   or a pharmaceutically acceptable salt or a stereoisomer thereof.   
     
     
         72 . A pharmaceutical composition comprising a compound of  claim 39 , or a pharmaceutically acceptable salt or a stereoisomer thereof and a pharmaceutically acceptable carrier or excipient. 
     
     
         73 . A method of inhibiting PD-1/PD-L1 interaction, said method comprising administering to an individual a compound of  claim 39 , or a pharmaceutically acceptable salt or a stereoisomer thereof. 
     
     
         74 . A method of treating a disease or disorder in a subject, said method comprising administering to the subject in need thereof a therapeutically effective amount of a compound of  claim 39 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the compound binds to PD-L1. 
     
     
         75 . The method of  claim 73 , wherein the compound further induces PD-L1 internalization. 
     
     
         76 . The method of  claim 75 , wherein the compound induces PD-L1 dimerization, and wherein the dimerization occurs prior to PD-L1 internalization. 
     
     
         77 . The method of  claim 74 , wherein the disease or disorder is cancer. 
     
     
         78 . A method of enhancing, stimulating and/or increasing the immune response in a patient, said method comprising administering to the patient in need thereof a therapeutically effective amount of a compound of  claim 39 , or a pharmaceutically acceptable salt or a stereoisomer thereof.