Heterocyclic compounds as adenosine antagonists

A compound of the formula (I):

• or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
• A is 4-hydroxyphenyl optionally further substituted by R3, 4-hydroxy-2-pyridyl optionally further substituted by R4, a naphthyl substituted by R4, a 9- or 10-membered bicyclic heterocyclyl optionally substituted by R4, or a 10-membered bicyclic heteroaryl optionally substituted by R4;
• B is a phenyl optionally substituted by R3, C3-C6 cycloalkyl optionally substituted by R4, 3- to 6-membered heterocyclyl optionally substituted by R4 or a 5- to 10-membered heteroaryl optionally substituted by R4;
• R1 is a hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 6-membered heterocyclyl, 5- to 10-membered heteroaryl, —(C1-C3 alkylene)(C3-C6 cycloalkyl), —(C1-C3 alkylene)(3-6-membered heterocyclyl), —(C1-C3 alkylene)(5-6-membered heteroaryl), —(C1-C3 alkylene)(C6 aryl), —C(O)R1a, —C(O)OR1a, —C(O)NR1bR1c, —NR1bR1c, —S(O)2R1a, —(C1-C3 alkylene)C(O)NR1bR1c, —(C1-C3 alkylene)C(O)R1a or —(C1-C3 alkylene)NR1bR1c, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 6-membered heterocyclyl, 5- to 10-membered heteroaryl, —(C1-C3 alkylene)(C3-C6 cycloalkyl), —(C1-C3 alkylene)(3-6-membered heterocyclyl), —(C1-C3 alkylene)(5-6-membered heteroaryl), and —(C1-C3 alkylene)(C6 aryl) of R1 are independently optionally substituted by R4;
• each R1a is independently hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, 3-6-membered heterocyclyl, C6 aryl, 5-6-membered heteroaryl, —(C1-C3 alkylene)(C3-C6 cycloalkyl), —(C1-C3 alkylene)(3-6-membered heterocyclyl), —(C1-C3 alkylene)(C6 aryl) or —(C1-C3 alkylene)(5-6-membered heteroaryl), wherein each of which is optionally substituted by methyl, ethyl, halogen, oxo, —CF3, —OH, —OCH3, —CN, —C(O)OCH3, —C(O)OC2H5, —NH2 or —NHCH3;
• each R1b and R1c is independently hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, 3-6-membered heterocyclyl, C6 aryl, 5-6-membered heteroaryl, —(C1-C3 alkylene)(C3-C6 cycloalkyl), —(C1-C3 alkylene)(3-6-membered heterocyclyl), —(C1-C3 alkylene)(C6 aryl) or —(C1-C3 alkylene)(5-6-membered heteroaryl), wherein each of which is optionally substituted by methyl, ethyl, halogen, oxo, —CF3, —OH, —OCH3, —CN, —C(O)OCH3, —C(O)OC2H5, —NH2 or —NHCH3;
• or R1b and R1c are taken together with the nitrogen atom to which they are attached to form a 3- to 6-membered heterocyclyl;
• R2 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C14 aryl, C5-C14 heteroaryl, C3-C6 cycloalkyl, 3- to 6-membered heterocyclyl, —CN, halogen, —OR2a, —SR2a, —NR2bR2c, —C(O)R2a, —NR2bC(O)R2c, —NR2aC(O)NR2bR2c, —C(O)OR2a, —C(O)ONR2bR2c or —C(O)NR2bR2c, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C14 aryl, C3-C6 cycloalkyl and 3- to 6-membered heterocyclyl of R2 are independently optionally substituted by R4;
• each R2a is independently hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, 3- to 6-membered heterocyclyl, C6-aryl, 5- to 6-membered heteroaryl, —(C1-C3 alkylene)N(C2H5)2, —(C1-C3 alkylene)(C3-C6 cycloalkyl), —(C1-C3 alkylene)(3-6-membered heterocyclyl), —(C1-C3 alkylene)(5-6-membered heteroaryl) or —(C1-C3 alkylene)(C6 aryl), wherein each of which is optionally substituted by methyl, ethyl, halogen, oxo, —CF3, —OH, —OCH3, —CN, —C(O)OCH3, —C(O)OC2H5, —NH2 or —NHCH3;
• each R2b and R2c is independently hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, 3- to 6-membered heterocyclyl, C6-aryl, 5- to 6-membered heteroaryl, —(C1-C3 alkylene)N(C2H5)2, —(C1-C3 alkylene)(C3-C6 cycloalkyl), —(C1-C3 alkylene)(3-6-membered heterocyclyl), —(C1-C3 alkylene)(C6 aryl) or —(C1-C3 alkylene)(5-6-membered heteroaryl), wherein each of which is optionally substituted by methyl, ethyl, halogen, oxo, —CF3, —OH, —OCH3, —CN, —C(O)OCH3, —C(O)OC2H5, —NH2 or —NHCH3;
• or R2b and R2′ are taken together with the nitrogen atom to which they are attached to form a 3- to 6-membered heterocyclyl;
• each R3 is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, —CN, —OR5, —SR5, —NR6R7, —NO2, —C═NH(OR5), —C(O)R5, —OC(O)R5, —C(O)OR5, —C(O)NR6R7, —OC(O)NR6R7, —NR5C(O)R6, —NR5C(O)OR6, —NR5C(O)NR6R7, —S(O)R5, —S(O)2R5, —NR5S(O)R6, —C(O)NR5S(O)R6, —NR5S(O)2R6, —C(O)NR5S(O)2R6, —S(O)NR6R7, —S(O)2NR6R7, —P(O)(OR6) (OR7), C3-C6 cycloalkyl, 3-12-membered heterocyclyl, 5- to 10-membered heteroaryl, C6-C14 aryl, —(C1-C3 alkylene)CN, —(C1-C3 alkylene)OR5, —(C1-C3 alkylene)SR5, —(C1-C3 alkylene)NR6R7, —(C1-C3 alkylene)CF3, —(C1-C3 alkylene)NO2, —C═NH(OR5), —(C1-C3 alkylene)C(O)R5, —(C1-C3 alkylene)OC(O)R5, —(C1-C3 alkylene)C(O)OR5, —(C1-C3 alkylene)C(O)NR6R7, —(C1-C3 alkylene)OC(O)NR6R7, —(C1-C3 alkylene)NR5C(O)R6, —(C1-C3 alkylene)NR5C(O)OR6, —(C1-C3 alkylene)NR5C(O)NR6R7, —(C1-C3 alkylene)S(O)R5, —(C1-C3 alkylene)S(O)2R5, —(C1-C3 alkylene)NR5S(O)R6, —C(O)(C1-C3 alkylene)NR5S(O)R6, —(C1-C3 alkylene)NR5S(O)2R6, —(C1-C3 alkylene)C(O)NR5S(O)2R6, —(C1-C3 alkylene)S(O)NR6R7, —(C1-C3 alkylene)S(O)2NR6R7, —(C1-C3 alkylene)P(O)(OR6)(OR7), —(C1-C3 alkylene)(C3-C6 cycloalkyl), —(C1-C3 alkylene)(3-12-membered heterocyclyl), —(C1-C3 alkylene)(5-10-membered heteroaryl) or —(C1-C3 alkylene)(C6-C14 aryl), wherein each R3 is independently optionally substituted by halogen, oxo, —OR8, —NR8R9, —C(O)R8, —CN, —S(O)R8, —S(O)2R8, —P(O)(OR8)(OR9), —(C1-C3 alkylene)OR8, —(C1-C3 alkylene)NR8R9, —(C1-C3 alkylene)C(O)R8, —(C1-C3 alkylene)S(O)R8, —(C1-C3 alkylene)S(O)2R8, —(C1-C3 alkylene)P(O)(OR8)(OR9), C3-C8 cycloalkyl, or C1-C6 alkyl optionally substituted by oxo, —OH or halogen;
• each R4 is independently oxo or R3;
• R5 is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5-6-membered heteroaryl or 3-6-membered heterocyclyl, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5-6-membered heteroaryl and 3-6-membered heterocyclyl of R5 are independently optionally substituted by halogen, oxo, —CN, —OR9, —NR9R10, —P(O)(OR9)(OR10), phenyl optionally substituted by halogen, or C1-C6 alkyl optionally substituted by halogen, —OH or oxo;
• R6 and R7 are each independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5-6-membered heteroaryl, —(C1-C3 alkylene)(C6 aryl) or 3-6 membered heterocyclyl, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5-6-membered heteroaryl, —(C1-C3 alkylene)(C6 aryl) and 3-6 membered heterocyclyl of R6 and R7 are independently optionally substituted by halogen, oxo, —CN, —OR9, —NR9R10 or C1-C6 alkyl optionally substituted by halogen, —OH or oxo;
• or R6 and R7 are taken together with the atom to which they attached to form a 3-6 membered heterocyclyl optionally substituted by halogen, oxo, —OR9, —NR9R10 or C1-C6 alkyl optionally substituted by halogen, oxo or —OH;
• R8 and R9 in R3 are each independently hydrogen, C1-C6 alkyl optionally substituted by halogen or oxo, C2-C6 alkenyl optionally substituted by halogen or oxo, or C2-C6 alkynyl optionally substituted by halogen or oxo;
• or R8 and R9 in R3 are taken together with the atom to which they attached to form a 3-6 membered heterocyclyl optionally substituted by halogen, oxo or C1-C6 alkyl optionally substituted by halogen or oxo;
• and
• R9 and R10 in R5, R6 and R7 are each independently hydrogen, C1-C6 alkyl optionally substituted by halogen or oxo, C2-C6 alkenyl optionally substituted by halogen or oxo, or C2-C6 alkynyl optionally substituted by halogen or oxo;
• or R9 and R10 in R5, R6 and R7 are taken together with the atom to which they attached to form a 3-6 membered heterocyclyl optionally substituted by halogen, oxo or C1-C6 alkyl optionally substituted by oxo or halogen.