# US 11,028,058 B2 · Heterocyclic compounds as adenosine antagonists

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- Number: US 11,028,058 B2
- Document ID: US11028058B2
- Status: Granted
- Kind: B2
- Application number: 16/039,307
- Filed: 2018-07-18
- Published: 2019-01-24
- Granted: 2021-06-08
- Earliest claimed: 2017-07-18
- Assignees: Nuvation Bio Inc.
- Applicants: Nuvation Bio Inc.
- Inventors: Son Minh Pham; Jiyun Chen; Amantullah Ansari; Pradeep S. Jadhavar; Varshavekumar S. Patil; Farha Khan; Sreekanth A. Ramachandran; Anil Kumar Agarwal; Sarvajit Chakravarty
- Web page: https://patentgrep.com/patent/US11028058B2

## CPC

- C07D 241/20: Nitrogen atoms (nitro radicals C07D241/16)
- A61P 35/00: Antineoplastic agents
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/14: containing three or more hetero rings
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 403/14: containing three or more hetero rings
- C07D 405/14: containing three or more hetero rings
- C07D 407/04: directly linked by a ring-member-to-ring-member bond
- C07D 409/14: containing three or more hetero rings
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/14: containing three or more hetero rings
- C07D 417/04: directly linked by a ring-member-to-ring-member bond
- C07D 417/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Aminopyrazine compounds as modulators of an adenosine receptor are provided. The compounds may find use as therapeutic agents for the treatment of diseases mediated through a G-protein-coupled receptor signaling pathway and may find particular use in oncology.

## Claims

### Claim 1

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.

### Claim 2 (depends on 1)

The compound of claim 1, 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, or a 10-membered bicyclic heteroaryl optionally substituted by R4;
B is a phenyl optionally substituted by R3, or 5- to 6-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, —C(O)R1a, —C(O)OR1a, —C(O)NR1bR1c, or —NR1bR1c, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl and 3- to 6-membered heterocyclyl of R1 are independently optionally substituted by R4;
each R1a is independently hydrogen, C1-C6 alkyl, or C3-C6 cycloalkyl;
each R1b and R1c is independently hydrogen, C1-C6 alkyl, or C3-C6 cycloalkyl;
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, —CN, halogen, —OR2a, —NR2bR2″, —C(O)R2a, —C(O)OR2a, or—C(O)NR2bR2′, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl and C6-C14 aryl of R2 are independently optionally substituted by R4;
each R2a is independently hydrogen, C1-C6 alkyl, or C3-C6 cycloalkyl;
each R2b and R2c is independently hydrogen, C1-C6 alkyl, or C3-C6 cycloalkyl;
or R2b and R2c 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 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 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 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 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 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 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.

### Claim 3 (depends on 1)

The compound of claim 1, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1 is hydrogen or —C(O)R1a.

### Claim 4 (depends on 3)

The compound of claim 3, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1 is hydrogen.

### Claim 5 (depends on 3)

The compound of claim 3, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1 is —C(O)R1a and R1a is C1-C6 alkyl.

### Claim 6 (depends on 1)

The compound of claim 1, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R2 is hydrogen, C1-C6 alkyl, —CN, halogen, —OR2a.

### Claim 7 (depends on 6)

The compound of claim 6, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R2 is hydrogen.

### Claim 8 (depends on 6)

The compound of claim 6, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R2 is C1-C6 alkyl.

### Claim 9 (depends on 6)

The compound of claim 6, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R2 is CN or halogen.

### Claim 10 (depends on 6)

The compound of claim 6, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R2 is —OR2a and R2a is C1-C6 alkyl.

### Claim 11 (depends on 1)

The compound of claim 1, 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 or 4-hydroxy-2-pyridyl optionally further substituted by R4.

### Claim 12 (depends on 11)

The compound of claim 11, 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.

### Claim 13 (depends on 11)

The compound of claim 11, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein A is 4-hydroxy-2-pyridyl optionally further substituted by R4.

### Claim 14 (depends on 1)

The compound of claim 1, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein A is a 10-membered bicyclic heteroaryl optionally substituted by R4.

### Claim 15 (depends on 1)

The compound of claim 1, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the A is selected from the group consisting of quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, cinnolinyl, and naphthyridinyl, each of which is optionally substituted by R4.

### Claim 16 (depends on 15)

The compound of claim 15, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R4 is R3 and each R3 is independently selected from the group consisting of halogen, —CN, —OR5, —SR5, —NR6R7, —NO2, —C(O)R5, —C(O)OR5, —C(O)NR6R7, —C(O)NR5S(O)2R6, —OC(O)R5, —OC(O)NR6R7, —NR5C(O)R6, —NR5C(O)NR6R7, —S(O)R5, —S(O)2R5, C3-C6 cycloalkyl and C1-C6 alkyl optionally substituted by halogen.

### Claim 17 (depends on 16)

The compound of claim 16, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein each R3 is independently selected from the group consisting of halogen, —OR5 and C1-C6 alkyl optionally substituted by halogen.

### Claim 18 (depends on 1)

The compound of claim 1, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein A is selected from the group consisting of:

### Claim 19 (depends on 1)

The compound of claim 1, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein A is selected from the group consisting of:

### Claim 20 (depends on 1)

The compound of claim 1, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein B is a phenyl optionally substituted by R3.

### Claim 21 (depends on 1)

The compound of claim 1, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein B is a 5- to 6-membered heteroaryl optionally substituted by R4.

### Claim 22 (depends on 21)

The compound of claim 21, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the B is a 5-membered heteroaryl selected from the group consisting of furanyl, oxazolyl, thiophenyl, pyrazolyl, isoxazolyl, 1,3,4-oxadiazolyl, imidazolyl, thiazolyl, isothiazolyl, triazolyl, 1,3,4-thiadiazolyl and tetrazolyl, which is optionally substituted by R4.

### Claim 23 (depends on 21)

The compound of claim 21, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the B is a 6-membered heteroaryl selected from the group consisting of pyridyl and pyrimidinyl, which is optionally substituted by R4.

### Claim 24 (depends on 21)

The compound of claim 21, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R4 is R3 and R3 is selected from the group consisting of halogen, —OR5, —NR6R7, —C(O)R5, C3-C6 cycloalkyl and C1-C6 alkyl optionally substituted by halogen.

### Claim 25 (depends on 24)

The compound of claim 24, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R3 is selected from the group consisting of halogen and C1-C6 alkyl optionally substituted by halogen.

### Claim 26 (depends on 1)

The compound of claim 1, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein B is selected from the group consisting of:

### Claim 27 (depends on 1)

The compound of claim 1, wherein the compound is of the formula (II):
or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1, R2 and B are as defined for formula (I);
X is N or CH;
each R3 is independently halogen, —CN, —OR5, —SR5, —NR6R7, —NO2, —C(O)R5, —C(O)OR5, —C(O)NR6R7, —C(O)NR5S(O)2R6, —OC(O)R5, —OC(O)NR6R7, —NR5C(O)R6, —NR5C(O)NR6R7, —S(O)R5, —S(O)2R5, C3-C6 cycloalkyl, or C1-C6 alkyl optionally substituted by halogen;
each R5 is independently hydrogen, C1-C6 alkyl, or C3-C6 cycloalkyl;
R6 and R7 are each independently hydrogen, C1-C6 alkyl, or C3-C6 cycloalkyl;
or R6 and R7 are taken together with the atom to which they attached to form a 3-6 membered heterocyclyl; and
n is 0, 1, 2 or 3.

### Claim 28 (depends on 27)

The compound of claim 27, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R3 is selected from the group consisting of halogen, —OR5 and C1-C6 alkyl optionally substituted by halogen.

### Claim 29 (depends on 1)

The compound of claim 1, wherein the compound is of the formula (IVc):
or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1, R2 and B are as defined for formula (I);
each X3 is independently CR4, CH or N;
each R4 is independently halogen, —CN, —OR5, —SR5, —NR6R7, —NO2, —C(O)R5, —C(O)OR5, —C(O)NR6R7, —C(O)NR5S(O)2R6, —OC(O)R5, —OC(O)NR6R7, —NR5C(O)R6, —NR5C(O)NR6R7, —S(O)R5, —S(O)2R5, C3-C6 cycloalkyl, or C1-C6 alkyl optionally substituted by halogen;
where each R5 is independently hydrogen, C1-C6 alkyl, or C3-C6 cycloalkyl; and
R6 and R7 are each independently hydrogen, C1-C6 alkyl, or C3-C6 cycloalkyl;
or R6 and R7 are taken together with the atom to which they attached to form a 3-6 membered heterocyclyl.

### Claim 30 (depends on 29)

The compound of claim 29, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R4 is selected from the group consisting of halogen, —OR5 and C1-C6 alkyl optionally substituted by halogen.

### Claim 31 (depends on 29)

The compound of claim 29, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein one of X3 is N, and the remaining X3 are each CR4.

### Claim 32 (depends on 29)

The compound of claim 29, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein two of X3 are N, and the remaining X3 are each CR4.

### Claim 33

A compound selected from the group consisting of
or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

### Claim 34 (depends on 33)

The compound of claim 33, or a pharmaceutically acceptable salt thereof.

### Claim 35 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable carrier.

### Claim 36 (depends on 1)

A method of treating disease mediated by an adenosine signaling pathway in an individual in need thereof comprising administering to the individual a therapeutically effective amount of a compound of claim 1, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

### Claim 37 (depends on 1)

A method of treating cancer in an individual in need thereof comprising administering to the individual a therapeutically effective amount of a compound of claim 1, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

### Claim 38 (depends on 1)

A method of inhibiting an adenosine receptor of subtype A2A, A2B or A3 in a cell, comprising administering a compound of claim 1, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, to the cell.

### Claim 39 (depends on 38)

The method of claim 38, wherein the adenosine receptor is of subtype A2A.

### Claim 40 (depends on 1)

A kit comprising a compound of claim 1, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

### Claim 41 (depends on 33)

The compound of claim 33, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

### Claim 42 (depends on 41)

The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein the compound is

### Claim 43 (depends on 41)

The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein the compound is

### Claim 44 (depends on 41)

The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein the compound is

### Claim 45 (depends on 41)

The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein the compound is

### Claim 46 (depends on 41)

The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein the compound is

### Claim 47 (depends on 41)

The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein the compound is

### Claim 48 (depends on 41)

The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein the compound is

### Claim 49 (depends on 41)

The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein the compound is

### Claim 50 (depends on 41)

The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein the compound is

### Claim 51 (depends on 41)

The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein the compound is

### Claim 52 (depends on 41)

The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein the compound is