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US 2025/0333418 A1Published application
Purine compounds, compositions comprising them and uses thereof
OwnerJeremy Green, Shawn Gallagher-Duval +3inventors
InventorsJeremy Green, Shawn Gallagher-Duval, Alexandre Lemire, Yuchen Zhou, Hong Wang
Life of this patent
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Abstract
The present document relates to purine compounds, pharmaceutical compositions comprising the same and their use in the treatment or prevention of diseases and disorders associated with the cannabinoid CB1 receptor. For example, the purine compounds, or a tautomeric form and/or salt thereof, are of the formula (I): wherein R1 to R4 are as defined herein.
Claims30
-119. (canceled)
A compound of Formula I:
- wherein,
- R1 is an optionally substituted C6aryl group;
- R2 is an optionally substituted C6aryl or C5-C6heteroaryl group;
- R3 is an optionally substituted group selected from R7O—, N(R8)2—, C4-10heterocycloalkyl, and C5-6heteroaryl;
- R4 is an optionally substituted group selected from R5O— and N(R6)2—;
- R5 is a group selected from C1-C6alkyl, C3-C7cycloalkyl, C4-C10heterocycloalkyl, C5-C6heteroaryl, C3-C7cycloalkylC1-C3alkyl, C4-C10heterocycloalkylC1-C3alkyl, C5-C6heteroarylC1-C3alkyl;
- R6 is H or a group selected from C1-C6alkyl, C3-C7cycloalkyl, C4-C10heterocycloalkyl, C5-C6heteroaryl, C3-C7cycloalkylC1-C3alkyl, C4-C10heterocycloalkylC1-C3alkyl, C5-C6heteroarylC1-C3alkyl, wherein at least one R6 is other than H, or two R6 groups are taken together with their adjacent nitrogen atom to form a C4-C10heterocycloalkyl or C5-C6heteroaryl group;
- wherein at least one of said alkyl, cycloalkyl, heterocycloalkyl, or heteroaryl in R5 or R6 is substituted with at least one hydroxyl or hydroxy-substituted C1-C4alkyl group and is optionally further substituted with other substituents;
- R7 is an optionally substituted C1-C6alkyl;
- and
- R8 is independently in each occurrence selected from hydrogen, C1-C6alkyl, C3-C7cycloalkyl, and C4-C10heterocycloalkyl;
- wherein each of the alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups is optionally substituted;
- or a pharmaceutically acceptable salt thereof.
10 more elements
A compound of Formula IV:
- wherein,
- m is 0, 1, 2, or 3;
- n is 0 or 1;
- p is 0, 1, 2, or 3;
- X1 is C and X2 to X6 are each independently selected from N and CR21 and n is 1, wherein at most three of X2 to X6 are N;
- or X1 is C or N and X2 to X5 are each independently selected from CR21, O, S, N, or NR11, n is zero and X6 is absent and forms a bond between X1 and X5, wherein at most three of X1 to X5 are other than C or CR21;
- X7 and X8 are each independently selected from O, S, SO2, NR36, or C(R35)2, wherein when one of X7 and X8 is O, S, or NR36, then the other is C(R35)2;
- R12 is independently in each occurrence selected from F, Cl, CN, NH2, N(H)C1-C3alkyl, N(C1-C3alkyl)2, and C1-C3alkyl, and p is 0, 1, 2, or 3;
- R14 is N(R16)2— or optionally substituted C5-C6heteroaryl;
- and
- R16 is selected from H or a group selected from optionally substituted C1-C6alkyl, C3-C7cycloalkyl, C4-C10heterocycloalkyl, C5-C6heteroaryl, C3-C7cycloalkylC1-C3alkyl, C4-C10heterocycloalkylC1-C3alkyl, C5-C6heteroarylC1-C3alkyl, or two R16 groups are taken together with their adjacent nitrogen atom to form an optionally substituted C4-C10heterocycloalkyl or C5-C6heteroaryl;
- and
- R31 to R34 are independently in each occurrence selected from hydrogen, halogen, OH, OR9, CN, NO2, C(O)OH, C(O)OR9, C(O)R9, C(O)N(R10)2, C(R11)═NR11, SO2R9, SO2N(R10)2, N(R11)C(O)R9, N(R11)SO2R9, N(R11)C(O)N(R10)2, N(R11)SO2N(R10)2, N(R10)2, P(O)(R10)2, P(O)(OR10)2, B(OR10)2, and optionally substituted C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C6-10aryl, C5-10heteroaryl, C3-10cycloalkyl, and C4-10heterocycloalkyl groups;
- or a pharmaceutically acceptable salt thereof.
11 more elements
A compound of Formula V:
- wherein,
- n is 0 or 1;
- p is 0, 1, 2, or 3;
- X1 is C and X2 to X6 are each independently selected from N and CR21 and n is 1, wherein at most three of X2 to X6 are N;
- or X1 is C or N and X2 to X5 are each independently selected from CR21, O, S, N, or NR11, n is zero and X6 is absent and forms a bond between X1 and X5, wherein at most three of X1 to X5 are other than C or CR21;
- R12 is independently in each occurrence selected from F, Cl, CN, NH2, N(H)C1-C3alkyl, N(C1-C3alkyl)2, and C1-C3alkyl;
- R13 is an optionally substituted group selected from R7O—, N(R8)2—, and C5-6heteroaryl;
- and
- R14 is N(R16)2— or optionally substituted C5-C6heteroaryl;
- or a pharmaceutically acceptable salt thereof.
7 more elements
A compound of Formula VI:
- wherein,
- m is 0, 1, 2, or 3;
- n is 0 or 1;
- p is 0, 1, 2, or 3;
- X1 is C and X2 to X6 are each independently selected from N and CR21 and n is 1, wherein at most three of X2 to X6 are N;
- or X1 is C or N and X2 to X5 are each independently selected from CR21, O, S, N, or NR11, n is zero and X6 is absent and forms a bond between X1 and X5, wherein at most three of X1 to X5 are other than C or CR21;
- X7 and X8 are each independently selected from O, S, SO2, NR36, or C(R35)2, wherein when one of X7 and X8 is O, S, or NR36, then the other is C(R35)2;
- R12 is independently in each occurrence selected from F, Cl, CN, NH2, N(H)C1-C3alkyl, N(C1-C3alkyl)2, and C1-C3alkyl, and p is 0, 1, 2, or 3;
- R15 is a group selected from C1-C6alkyl, C3-C7cycloalkyl, C4-C10heterocycloalkyl, C5-C6heteroaryl, C3-C7cycloalkylC1-C3alkyl, C4-C10heterocycloalkylC1-C3alkyl, C5-C6heteroarylC1-C3alkyl;
- and
- R31 to R34 are independently in each occurrence selected from hydrogen, halogen, OH, OR9, CN, NO2, C(O)OH, C(O)OR9, C(O)R9, C(O)N(R10)2, C(R11)═NR11, SO2R9, SO2N(R10)2, N(R11)C(O)R9, N(R11)SO2R9, N(R11)C(O)N(R10)2, N(R11)SO2N(R10)2, N(R10)2, P(O)(R10)2, P(O)(OR10)2, B(OR10)2, and optionally substituted C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C6-10aryl, C5-10heteroaryl, C3-10cycloalkyl, and C4-10heterocycloalkyl groups;
- or a pharmaceutically acceptable salt thereof.
9 more elements
A compound of Formula VII:
- wherein,
- n is 0 or 1;
- p is 0, 1, 2, or 3;
- X1 is C and X2 to X6 are each independently selected from N and CR21 and n is 1, wherein at most three of X2 to X6 are N;
- or X1 is C or N and X2 to X5 are each independently selected from CR21, O, S, N, or NR11, n is zero and X6 is absent and forms a bond between X1 and X5, wherein at most three of X1 to X5 are other than C or CR21;
- R12 is independently in each occurrence selected from F, Cl, CN, NH2, N(H)C1-C3alkyl, N(C1-C3alkyl)2, and C1-C3alkyl;
- R13 is an optionally substituted group selected from R7O—, N(R8)2—, and C5-6heteroaryl;
- and
- R15 is a group selected from C1-C6alkyl, C3-C7cycloalkyl, C4-C10heterocycloalkyl, C5-C6heteroaryl, C3-C7cycloalkylC1-C3alkyl, C4-C10heterocycloalkylC1-C3alkyl, C5-C6heteroarylC1-C3alkyl;
- or a pharmaceutically acceptable salt thereof.
7 more elements
A compound of Formula VIII:
- wherein,
- m is 0, 1, 2, or 3;
- n is 0 or 1;
- p is 0, 1, 2, or 3;
- X1 is C and X2 to X6 are each independently selected from N and CR21 and n is 1, wherein at most three of X2 to X6 are N;
- or X1 is C or N and X2 to X5 are each independently selected from CR21, O, S, N, or NR11, n is zero and X6 is absent and forms a bond between X1 and X5, wherein at most three of X1 to X5 are other than C or CR21;
- X7 and X8 are each independently selected from O, S, SO2, NR36, or C(R35)2, wherein when one of X7 and X8 is O, S, or NR36, then the other is C(R35)2;
- R9 is independently in each occurrence selected from optionally substituted C1-C6alkyl, C3-C7cycloalkyl, C4-C10heterocycloalkyl, C5-C6heteroaryl, C3-C7cycloalkylC1-C3alkyl, C4-C10heterocycloalkylC1-C3alkyl, and C5-C6heteroarylC1-C3alkyl;
- R10 is independently in each occurrence selected from H or a group selected from optionally substituted C1-C6alkyl, C3-C7cycloalkyl, C4-C10heterocycloalkyl, C5-C6heteroaryl, C3-C7cycloalkylC1-C3alkyl, C4-C10heterocycloalkylC1-C3alkyl, and C5-C6heteroarylC1-C3alkyl, or two R10 groups are taken together with their adjacent nitrogen atom to form an optionally substituted C4-C10heterocycloalkyl or C5-C6heteroaryl;
- R11 is independently in each occurrence selected from H or a group selected from optionally substituted C1-C6alkyl, C3-C7cycloalkyl, C4-C10heterocycloalkyl, C5-C6heteroaryl, C3-C7cycloalkylC1-C3alkyl, C4-C10heterocycloalkylC1-C3alkyl, C5-C6heteroarylC1-C3alkyl;
- R12 is independently in each occurrence selected from F, Cl, CN, NH2, N(H)C1-C3alkyl, N(C1-C3alkyl)2, and C1-C3alkyl;
- R24 is selected from Cl, CN, C(O)OH, R9C(O)N(R11)—, R9C(O)NHC(NH)NH—, R9S(O)2—, N(R10)2C(O)—, and an optionally substituted C1-C6alkyl group;
- and
- R31 to R34 are independently in each occurrence selected from hydrogen, halogen, OH, OR9, CN, NO2, C(O)OH, C(O)OR9, C(O)R9, C(O)N(R10)2, C(R11)═NR11, SO2R9, SO2N(R10)2, N(R11)C(O)R9, N(R11)SO2R9, N(R11)C(O)N(R10)2, N(R11)SO2N(R10)2, N(R10)2, P(O)(R10)2, P(O)(OR10)2, B(OR10)2, and optionally substituted C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C6-10aryl, C5-10heteroaryl, C3-10cycloalkyl, and C4-10heterocycloalkyl groups;
- or a pharmaceutically acceptable salt thereof.
12 more elements
A compound of Formula IX:
- wherein,
- X1 is C and X2 to X6 are each independently selected from N and CR21 and n is 1, wherein at most three of X2 to X6 are N;
- or X1 is C or N and X2 to X5 are each independently selected from CR21, O, S, N, or NR11, n is zero and X6 is absent and forms a bond between X1 and X5, wherein at most three of X1 to X5 are other than C or CR21;
- R12 is independently in each occurrence selected from F, Cl, CN, NH2, N(H)C1-C3alkyl, N(C1-C3alkyl)2, and C1-C3alkyl;
- R13 is an optionally substituted group selected from R7O—, N(R8)2—, and C5-6heteroaryl;
- and
- R24 is selected from Cl, CN, C(O)OH, R9C(O)N(R11)—, R9C(O)NHC(NH)NH—, R9S(O)2—, N(R10)2C(O)—, and an optionally substituted C1-C6alkyl group;
- or a pharmaceutically acceptable salt thereof.
5 more elements
A compound selected from compounds 1 to 158 and 160 to 240, or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.