US2021040097A1PendingUtilityA1
Adenosine receptor antagonists and uses thereof
Est. expiryMar 5, 2038(~11.6 yrs left)· nominal 20-yr term from priority
C07F 9/65616A61K 9/2054C07D 473/06A61P 35/00A61P 25/00A61P 13/12A61P 11/00A61P 9/00A61P 3/10A61P 3/04A61P 1/16A61K 9/4858C07F 9/6561A61K 9/08A61K 9/4825
66
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Claims
Abstract
Disclosed herein are compounds, compositions, formulations, and methods for modulating the A2B adenosine receptor.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound represented by Formula (A):
or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 and R 2 are each independently selected from hydrogen, and substituted or unsubstituted alkyl;
R 3 is selected from substituted or unsubstituted phenyl, and substituted or unsubstituted heteroaryl, wherein if R 3 is substituted then R 3 is substituted with one or more groups selected from halogen, —CN, —OH, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 fluoroalkyl, C 1 -C 4 fluoroalkoxy, and substituted or unsubstituted C 1 -C 4 heteroalkyl;
R 4 is substituted or unsubstituted alkyl;
R 6 is hydrogen or substituted or unsubstituted alkyl;
or R 4 and R 6 are taken together with the carbon atom to which they are attached to form a carbonyl (C═O);
or R 4 and R 6 are taken together with the carbon atom to which they are attached to form a ring that is a substituted or unsubstituted C 3 -C 10 cycloalkyl, or substituted or unsubstituted C 2 -C 10 heterocycloalkyl, wherein if the ring is substituted then it is substituted with one or more R 15 ;
R 15 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted heteroaryl, -alkyl-(substituted or unsubstituted phenyl), -alkyl-(substituted or unsubstituted heteroaryl), —C(═O)R 16 , —C(═O)—OR 16 , —C(═O)N(R 16 ) 2 ;
each R 16 is independently selected from hydrogen and substituted or unsubstituted alkyl;
R 5 is hydrogen, R 7 , —C(═O)R 7 , —C(═O)—OR 7 , —C(═O)N(R 7 )(R 8 ), —C(═O)—SR 7 , or —P(═O)(OR 9 ) 2 ;
or R 4 and R 5 are taken together with the atoms to which they are attached to form a substituted or unsubstituted C 2 -C 10 heterocycloalkyl;
R 7 is substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted C 3 -C 10 cycloalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted heteroaryl, -alkyl-substituted or unsubstituted phenyl), -alkyl-(substituted or unsubstituted heteroaryl), -alkyl-(substituted or unsubstituted cycloalkyl), -alkyl-(substituted or unsubstituted heterocycloalkyl), —(C(R 10 ) 2 O) m —R 11 , —(CH 2 CH 2 O) n —R 11 , or —(C(R 10 ) 2 ) p —OR 11 ;
R 8 is hydrogen or alkyl;
or R 7 and R 8 are taken together with the nitrogen atom to which they are attached to form a substituted or unsubstituted C 2 -C 10 heterocycloalkyl;
each R 9 is independently selected from hydrogen and alkyl;
each R 10 is independently selected from hydrogen and alkyl;
R 11 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, —C(═O)R 12 , —C(═O)—OR 12 , —C(═O)N(R 12 )(R 8 ), —C(═O)—SR 12 , or —P(═O)(OR 9 ) 2 ;
R 12 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted C 3 -C 10 cycloalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted heteroaryl, -alkyl-(substituted or unsubstituted phenyl), or -alkyl-(substituted or unsubstituted heteroaryl);
m is 1, 2, 3, 4, 5, or 6;
n is 1, 2, 3, 4, 5, or 6;
p is 1, 2, 3, 4, 5, or 6;
wherein substituted means that the referenced group is substituted with one or more additional groups individually and independently selected from halogen, —CN, —NH 2 , —NH(alkyl), —N(alkyl) 2 , —OH, —CO 2 H, —CO 2 alkyl, —C(═O)NH 2 , —C(═O)NH(alkyl), —C(═O)N(alkyl) 2 , —S(═O) 2 NH 2 , —S(═O) 2 NH(alkyl), —S(═O) 2 N(alkyl) 2 , alkyl, cycloalkyl, fluoroalkyl, heteroalkyl, alkoxy, fluoroalkoxy, heterocycloalkyl, aryl, heteroaryl, aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone, and arylsulfone.
2 . The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 4 is C 1 -C 6 alkyl; R 6 is selected from hydrogen, and C 1 -C 6 alkyl; or R 4 and R 6 are taken together with the carbon atom to which they are attached to form a carbonyl (C═O).
3 . The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 4 is methyl, ethyl, or n-propyl; R 6 is selected from hydrogen, methyl, ethyl, and n-propyl; or R 4 and R 6 are taken together with the carbon atom to which they are attached to form a carbonyl (C═O).
4 . The compound of claim 3 , or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has the following structure of Formula (III):
or a pharmaceutically acceptable salt or solvate thereof.
5 . The compound of any one of claims 1 - 4 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 and R 2 are each independently selected from substituted or unsubstituted C 1 -C 6 alkyl; R 3 is selected from substituted or unsubstituted phenyl.
6 . The compound of any one of claims 1 - 4 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 and R 2 are each independently selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, n-pentyl, tert-pentyl, neopentyl, isopentyl, sec-pentyl, 3-pentyl, n-hexyl, isohexyl, 3-methylpentyl, 2,3-dimethylbutyl, and neohexyl.
7 . The compound of claim 6 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 is ethyl; R 2 is n-propyl; and R 3 is 3-(trifluoromethyl)phenyl.
8 . The compound of claim 4 , wherein the compound has the following structure:
or a pharmaceutically acceptable salt or solvate thereof.
9 . The compound of claim 8 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 5 is R 7 ; R 7 is C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted monocyclic C 3 -C 8 cycloalkyl, substituted or unsubstituted bicyclic C 5 -C 10 cycloalkyl, substituted or unsubstituted monocyclic C 2 -C 8 heterocycloalkyl, substituted or unsubstituted bicyclic C 5 -C 10 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic heteroaryl, —CH 2 -(substituted or unsubstituted phenyl), —CH 2 -(substituted or unsubstituted heteroaryl), —CH 2 -(substituted or unsubstituted C 2 -C 8 heterocycloalkyl), —CH(R 10 )O—R 11 , —(CH 2 CH 2 O) n —R 11 , or —(C(R 10 ) 2 ) p —OR 11 ; each R 10 is independently selected from hydrogen and methyl; R 11 is hydrogen, C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, —C(═O)R 12 , —C(═O)—OR 12 , —C(═O)N(R 12 )(R 8 ), —C(═O)—SR 12 , or —P(═O)(OR 9 ) 2 .
10 . The compound of claim 9 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 7 is C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, —CH 2 -(substituted or unsubstituted phenyl), —CH 2 -(substituted or unsubstituted heteroaryl), —CH 2 -(substituted or unsubstituted C 2 -C 8 heterocycloalkyl), —CH(R 10 )O—R 11 , or —(CH 2 CH 2 O) n —R 11 ; R 10 is hydrogen and methyl; R 11 is hydrogen, C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, —C(═O)R 12 , —C(═O)—OR 12 , —C(═O)N(R 12 )(R 8 ), —C(═O)—SR 12 , or —P(═O)(OH) 2 .
11 . The compound of claim 10 , wherein the compound has one of the following structures:
or a pharmaceutically acceptable salt or solvate thereof.
12 . The compound of claim 8 , wherein the compound has one of the following structures:
or a pharmaceutically acceptable salt or solvate thereof.
13 . The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has the following structure of Formula (I):
or a pharmaceutically acceptable salt or solvate thereof.
14 . The compound of claim 13 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 and R 2 are each independently selected from substituted or unsubstituted C 1 -C 6 alkyl; R 3 is selected from substituted or unsubstituted phenyl.
15 . The compound of claim 13 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 is ethyl; R 2 is n-propyl; and R 3 is 3-(trifluoromethyl)phenyl.
16 . The compound of claim 13 , or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has the following structure:
or a pharmaceutically acceptable salt or solvate thereof.
17 . The compound of claim 16 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 4 is methyl or ethyl; R 5 is hydrogen, R 7 , —C(═O)R 7 , —C(═O)—OR 7 , —C(═O)N(R 7 )(R 8 ), —C(═O)—SR 7 , or —P(═O)(OR 9 ) 2 ; R 7 is C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted monocyclic C 3 -C 8 cycloalkyl, substituted or unsubstituted bicyclic C 5 -C 10 cycloalkyl, substituted or unsubstituted monocyclic C 2 -C 8 heterocycloalkyl, substituted or unsubstituted bicyclic C 5 -C 10 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic heteroaryl, —CH 2 -(substituted or unsubstituted phenyl), —CH 2 -(substituted or unsubstituted heteroaryl), —CH 2 -(substituted or unsubstituted C 2 -C 8 heterocycloalkyl), —CH(R 10 )O—R 11 , —(CH 2 CH 2 O) n —R 11 , or —(C(R 10 ) 2 ) p —OR 11 ; each R 10 is independently selected from hydrogen and methyl; R 11 is hydrogen, C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, —C(═O)R 12 , —C(═O)—OR 12 , —C(═O)N(R 12 )(R 8 ), —C(═O)—SR 12 , or —P(═O)(OR 9 ) 2 .
18 . The compound of claim 16 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 5 is R 7 , —C(═O)R 7 , —C(═O)—OR 7 , —C(═O)N(R 7 )(R 8 ), —C(═O)—SR 7 , or —P(═O)(OH) 2 ; R 7 is C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted cyclohexyl, substituted or unsubstituted cyclopentyl, substituted or unsubstituted bicyclo[1.1.1]pentanyl, substituted or unsubstituted bicyclo[2.2.1]heptanyl, substituted or unsubstituted bicyclo[2.2.2]octanyl, substituted or unsubstituted bicyclo[3.2.1]octanyl, substituted or unsubstituted bicyclo[3.3.0]octanyl, substituted or unsubstituted bicyclo[4.3.0]nonanyl, or substituted or unsubstituted decalinyl, substituted or unsubstituted oxetanyl, substituted or unsubstituted tetrahydropyranyl, substituted or unsubstituted azetidinyl, substituted or unsubstituted pyrrolidinyl, substituted or unsubstituted piperidinyl, substituted or unsubstituted morpholinyl, substituted or unsubstituted thiomorpholinyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic heteroaryl, —CH 2 -(substituted or unsubstituted phenyl), —CH 2 -(substituted or unsubstituted heteroaryl), —CH 2 -(substituted or unsubstituted C 2 -C 8 heterocycloalkyl), —CH(R 10 )O—R 11 , —(CH 2 CH 2 O) n —R 11 , or —(C(R 10 ) 2 ) p —OR 11 ; each R 10 is independently selected from hydrogen and methyl; R 11 is hydrogen, C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, —C(═O)R 12 , —C(═O)—OR 12 , —C(═O)N(R 12 )(R 8 ), —C(═O)—SR 12 , or —P(═O)(OR 9 ) 2 .
19 . The compound of claim 16 , wherein the compound has one of the following structures:
or a pharmaceutically acceptable salt or solvate thereof.
20 . The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has the following structure of Formula (II):
wherein:
Y is selected from —CH 2 —, O, S, —NR 15 —, and —S(O) 2 —;
Z is O or S;
or a pharmaceutically acceptable salt or solvate thereof.
21 . The compound of claim 20 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 and R 2 are each independently selected from substituted or unsubstituted C 1 -C 6 alkyl; R 3 is selected from substituted or unsubstituted phenyl.
22 . The compound of claim 20 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 is ethyl; R 2 is n-propyl; and R 3 is 3-(trifluoromethyl)phenyl.
23 . The compound of claim 20 , or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has the following structure:
or a pharmaceutically acceptable salt or solvate thereof.
24 . The compound of claim 1 , wherein the compound has the following structure:
or a pharmaceutically acceptable salt or solvate thereof.
25 . The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has the following structure of Formula (IIa):
wherein:
Y is selected from —CH 2 —, O, S, —NR 15 —, and —S(O) 2 —;
or a pharmaceutically acceptable salt or solvate thereof.
26 . The compound of claim 25 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 and R 2 are each independently selected from substituted or unsubstituted C 1 -C 6 alkyl; R 3 is selected from substituted or unsubstituted phenyl.
27 . The compound of claim 25 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 is ethyl; R 2 is n-propyl; and R 3 is 3-(trifluoromethyl)phenyl.
28 . The compound of claim 25 , wherein the compound has the following structure:
or a pharmaceutically acceptable salt or solvate thereof.
29 . A compound represented by Formula (B):
or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 and R 2 are each independently selected from hydrogen, and substituted or unsubstituted alkyl;
R 3 is selected from substituted or unsubstituted phenyl, and substituted or unsubstituted heteroaryl, wherein if R 3 is substituted then R 3 is substituted with one or more groups selected from halogen, —CN, —OH, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 fluoroalkyl, C 1 -C 4 fluoroalkoxy, and substituted or unsubstituted C 1 -C 4 heteroalkyl;
R 4 is hydrogen or substituted or unsubstituted alkyl;
R 6 is hydrogen or substituted or unsubstituted alkyl;
or R 4 and R 6 are taken together with the carbon atom to which they are attached to form a carbonyl (C═O);
or R 4 and R 6 are taken together with the carbon atom to which they are attached to form a ring that is a substituted or unsubstituted C 3 -C 10 cycloalkyl, or substituted or unsubstituted C 2 -C 10 heterocycloalkyl, wherein if the ring is substituted then it is substituted with one or more R 15 ;
R 15 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted heteroaryl, -alkyl-(substituted or unsubstituted phenyl), -alkyl-(substituted or unsubstituted heteroaryl), —C(═O)R 16 , —C(═O)—OR 16 , —C(═O)N(R 16 ) 2 ;
each R 16 is independently selected from hydrogen and substituted or unsubstituted alkyl;
R 5 is substituted or unsubstituted C 3 -C 10 cycloalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted heteroaryl, -alkyl-(substituted or unsubstituted phenyl), -alkyl-(substituted or unsubstituted heteroaryl), -alkyl-(substituted or unsubstituted cycloalkyl), -alkyl-(substituted or unsubstituted heterocycloalkyl), —(C(R 10 ) 2 O) m —R 11 , —C(═O)—(C(R 10 ) 2 O) m —R 11 , —C(═O)—(CH 2 CH 2 O) n —R 11 , —C(═O)—R a or —C(═O)—OR 7 ;
R a is substituted or unsubstituted bicyclic cycloalkyl, substituted or unsubstituted bicyclic heterocycloalkyl, substituted or unsubstituted bicyclic heteroaryl, (substituted or unsubstituted heterocycloalkyl containing at least one O atom in the ring), substituted or unsubstituted azetidinyl, substituted or unsubstituted piperidinyl, substituted or unsubstituted azapenyl, substituted or unsubstituted 5-membered heteroaryl, substituted or unsubstituted pyridin-2-yl, substituted or unsubstituted pyridin-4-yl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted triazinyl;
or R 4 and R 5 are taken together with the atoms to which they are attached to form a substituted or unsubstituted C 2 -C 10 heterocycloalkyl;
R 7 is substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted C 3 -C 10 cycloalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted heteroaryl, -alkyl-(substituted or unsubstituted phenyl), -alkyl-(substituted or unsubstituted heteroaryl), -alkyl-(substituted or unsubstituted cycloalkyl), -alkyl-(substituted or unsubstituted heterocycloalkyl), —(C(R 10 ) 2 O) m —R 11 , —(CH 2 CH 2 O) n —R 11 , or —(C(R 10 ) 2 ) p —OR 11 ;
each R 9 is independently selected from hydrogen and alkyl;
each R 10 is independently selected from hydrogen and alkyl;
R 11 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, —C(═O)R 12 , —C(═O)—OR 12 , —C(═O)N(R 12 )(R 8 ), —C(═O)—SR 12 , or —P(═O)(OR 9 ) 2 ;
R 12 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted C 3 -C 10 cycloalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted heteroaryl, -alkyl-(substituted or unsubstituted phenyl), or -alkyl-(substituted or unsubstituted heteroaryl);
m is 1, 2, 3, 4, 5, or 6;
n is 1, 2, 3, 4, 5, or 6.
p is 1, 2, 3, 4, 5, or 6;
wherein substituted means that the referenced group is substituted with one or more additional groups individually and independently selected from halogen, —CN, —NH 2 , —NH(alkyl), —N(alkyl) 2 , —OH, —CO 2 H, —CO 2 alkyl, —C(═O)NH 2 , —C(═O)NH(alkyl), —C(═O)N(alkyl) 2 , —S(═O) 2 NH 2 , —S(═O) 2 NH(alkyl), —S(═O) 2 N(alkyl) 2 , alkyl, cycloalkyl, fluoroalkyl, heteroalkyl, alkoxy, fluoroalkoxy, heterocycloalkyl, aryl, heteroaryl, aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone, and arylsulfone.
30 . The compound of claim 29 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 4 is hydrogen; R 6 is hydrogen; R 5 is substituted or unsubstituted C 3 -C 10 cycloalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted heteroaryl, -alkyl-(substituted or unsubstituted phenyl), -alkyl-(substituted or unsubstituted heteroaryl), -alkyl-(substituted or unsubstituted cycloalkyl), -alkyl-(substituted or unsubstituted heterocycloalkyl), —(C(R 10 ) 2 O) m —R 11 , —C(═O)—(C(R 10 ) 2 O) m —R 11 , —C(═O)—(CH 2 CH 2 O) n —R 11 , —C(═O)—R a or —C(═O)—OR 7 .
31 . The compound of claim 29 or claim 30 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 and R 2 are each independently selected from substituted or unsubstituted C 1 -C 6 alkyl;
R 3 is selected from substituted or unsubstituted phenyl.
32 . The compound of claim 29 or claim 30 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 and R 2 are each independently selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, n-pentyl, tert-pentyl, neopentyl, isopentyl, sec-pentyl, 3-pentyl, n-hexyl, isohexyl, 3-methylpentyl, 2,3-dimethylbutyl, and neohexyl.
33 . The compound of claim 29 or claim 30 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 is ethyl;
R 2 is n-propyl; and
R 3 is 3-(trifluoromethyl)phenyl.
34 . The compound of claim 29 or claim 30 , wherein the compound has the following structure:
or a pharmaceutically acceptable salt or solvate thereof.
35 . The compound of claim 34 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 11 is hydrogen, substituted or unsubstituted alkyl, —C(═O)R 12 , —C(═O)—OR 12 , —C(═O)N(R 12 )(R 8 ), or —P(═O)(OR 9 ) 2 .
36 . The compound of claim 35 , wherein the compound has one of the following structures:
or a pharmaceutically acceptable salt or solvate thereof.
37 . The compound of claim 35 , wherein the compound has one of the following structures:
or a pharmaceutically acceptable salt or solvate thereof.
38 . The compound of claim 29 or claim 30 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 5 is —C(═O)—(C(R 10 ) 2 O) m —R 11 , —C(═O)—(CH 2 CH 2 O) n —R 11 , —C(═O)—R a or —C(═O)—OR 7 .
39 . The compound of claim 38 , wherein the compound has the following structure:
or a pharmaceutically acceptable salt or solvate thereof.
40 . The compound of claim 39 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R a is substituted or unsubstituted bicyclic cycloalkyl that is a fused bicyclic cycloalkyl, bridged bicyclic cycloalkyl, or spiro bicyclic cycloalkyl; or R a is substituted or unsubstituted bicyclic heterocycloalkyl that is a fused bicyclic heterocycloalkyl, bridged bicyclic heterocycloalkyl, or spiro bicyclic heterocycloalkyl; or R a is substituted or unsubstituted bicyclic heteroaryl.
41 . The compound of claim 39 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R a is substituted or unsubstituted bicyclo[1.1.1]pentanyl, substituted or unsubstituted bicyclo[2.2.1]heptanyl, substituted or unsubstituted bicyclo[2.2.2]octanyl, substituted or unsubstituted bicyclo[3.2.1]octanyl, substituted or unsubstituted bicyclo[3.3.0]octanyl, substituted or unsubstituted bicyclo[4.3.0]nonanyl, or substituted or unsubstituted decalinyl.
42 . The compound of claim 40 , wherein the compound has one of the following structures:
or a pharmaceutically acceptable salt or solvate thereof.
43 . The compound of claim 39 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R a is substituted or unsubstituted heterocycloalkyl containing at least one O atom in the ring, substituted or unsubstituted azetidinyl, substituted or unsubstituted piperidinyl, substituted or unsubstituted azapenyl, substituted or unsubstituted 5-membered heteroaryl, substituted or unsubstituted pyridin-2-yl, substituted or unsubstituted pyridin-4-yl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted triazinyl.
44 . The compound of claim 43 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R a is a substituted or unsubstituted heterocycloalkyl containing at least one O atom in the ring that is substituted or unsubstituted tetrahydrofuranyl, substituted or unsubstituted dihydrofuranyl, substituted or unsubstituted oxazolidinonyl, substituted or unsubstituted tetrahydropyranyl, substituted or unsubstituted dihydropyranyl, substituted or unsubstituted tetrahydrothiopyranyl, substituted or unsubstituted morpholinyl, substituted or unsubstituted oxetanyl, substituted or unsubstituted oxepanyl, substituted or unsubstituted oxazepinyl, or substituted or unsubstituted dioxanyl.
45 . The compound of claim 43 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R a is a substituted or unsubstituted 5-membered heteroaryl that is substituted or unsubstituted furanyl, substituted or unsubstituted thienyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted thiazolyl, substituted or unsubstituted imidazolyl, substituted or unsubstituted pyrazolyl, substituted or unsubstituted triazolyl, substituted or unsubstituted tetrazolyl, substituted or unsubstituted isoxazolyl, substituted or unsubstituted isothiazolyl, substituted or unsubstituted oxadiazolyl, or substituted or unsubstituted thiadiazolyl,
46 . The compound of claim 43 , wherein the compound has one of the following structures:
or a pharmaceutically acceptable salt or solvate thereof.
47 . The compound of claim 29 or claim 30 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 is ethyl;
R 2 is n-propyl;
R 3 is 3-(trifluoromethyl)phenyl;
R 5 is —C(═O)—(C(R 10 ) 2 O) m —R 11 , —C(═O)—(CH 2 CH 2 O) n —R 11 , or —C(═O)—OR 7 .
48 . The compound of claim 47 , wherein the compound has one of the following structures:
or a pharmaceutically acceptable salt or solvate thereof.
49 . The compound of claim 29 or claim 30 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
R 1 is ethyl;
R 2 is n-propyl;
R 3 is 3-(trifluoromethyl)phenyl;
R 5 is substituted or unsubstituted C 3 -C 10 cycloalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted heteroaryl, -alkyl-(substituted or unsubstituted phenyl), -alkyl-(substituted or unsubstituted heteroaryl), -alkyl-(substituted or unsubstituted cycloalkyl), -alkyl-(substituted or unsubstituted heterocycloalkyl).
50 . The compound of claim 49 , wherein the compound has the following structure:
or a pharmaceutically acceptable salt or solvate thereof.
51 . A pharmaceutical formulation, comprising a compound of any one of claims 1 - 50 , or any pharmaceutically acceptable salt or solvate thereof; and at least one pharmaceutically acceptable excipient.
52 . The pharmaceutical composition of claim 51 , wherein the pharmaceutical composition is formulated for administration to a mammal by oral administration, intravenous administration, or subcutaneous administration.
53 . The pharmaceutical composition of claim 51 , wherein the pharmaceutical composition is in the form of a tablet, a pill, a capsule, a liquid, a suspension, a dispersion, a solution, or an emulsion.
54 . A method of modulating the A 2 B adenosine receptor in a mammal comprising administering to the mammal a compound of any one of claims 1 - 50 , or any pharmaceutically acceptable salt or solvate thereof.
55 . A method of treating a disease or disorder in a mammal comprising administering to the mammal in need thereof a therapeutically effective amount of a compound of any one of claims 1 - 50 , or a pharmaceutically acceptable salt or solvate thereof, wherein the condition is selected from the group consisting of cardiovascular diseases, fibrosis, neurological disorders, type I hypersensitivity disorders, chronic and acute liver diseases, lung diseases, renal diseases, diabetes, obesity, and cancer.
56 . The method of claim 55 , wherein the condition is cancer.
57 . The method of any one of claims 54 - 56 , wherein the subject is human.Join the waitlist — get patent alerts
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