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US 2014/0275048 A1Published application
Prodrugs of fumarates and their use in treating various diseases
AssigneeAlkermes Pharma Ireland Limited
InventorsTarek A. Zeidan, Scott Duncan, Christopher P. Hencken, Thomas Andrew Wynn, Carlos N. Sanrame
Life of this patent
Estimating the term…
Abstract
The present invention provides compounds of formula (I), and pharmaceutical compositions thereof.
Claims15
A compound of Formula (I), or a pharmaceutically acceptable salt thereof:
- wherein:
- R1 is unsubstituted C1-C6 alkyl;
- La is unsubstituted C1-C6 alkyl linker, unsubstituted C3-C10 carbocycle, unsubstituted C6-C10 aryl, unsubstituted heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, or unsubstituted heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S;
- and
- R2 and R3 are each, independently, H, C1-C6 alkyl, C2-C6 alkenyl, C6-C10 aryl, C3-C10 carbocycle, heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, wherein the alkyl, alkenyl, aryl, carbocycle, heterocycle, or heteroaryl groups may be optionally independently substituted one or more times with C1-C3-alkyl, OH, O(C1-C4 alkyl), carbonyl, halo, NH2, N(H)(C1-C6 alkyl), N(C1-C6 alkyl)2, SO2H, SO2(C1-C6 alkyl), CHO, CO2H, CO2(C1-C6 alkyl), or CN;
- or alternatively, R2 and R3, together with the nitrogen atom to which they are attached, form a heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S;
- or a heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, wherein the heteroaryl or heterocycle may be optionally substituted one or more times with C1-C6 alkyl, CN, OH, halo, O(C1-C6 alkyl), CHO, carbonyl, thione, NO, or NH2.
4 more elements
A compound of Formula (Ia), or a pharmaceutically acceptable salt thereof:
- wherein:
- R1 is unsubstituted C1-C6 alkyl;
- La is substituted or unsubstituted C1-C6 alkyl linker, substituted or unsubstituted C3-C10 carbocycle, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, or substituted or unsubstituted heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S;
- and
- R2 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted C3-C10 carbocycle, substituted or unsubstituted heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, or substituted or unsubstituted heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S.
2 more elements
A compound of Formula (Ib):
- wherein:
- A− is a pharmaceutically acceptable anion;
- R1 is unsubstituted C1-C6 alkyl;
- La is substituted or unsubstituted C1-C6 alkyl linker, substituted or unsubstituted C3-C10 carbocycle, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, or substituted or unsubstituted heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S;
- R3′ is substituted or unsubstituted C1-C6 alkyl;
- and
- R2 and R3 are each, independently, H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted C3-C10 carbocycle, substituted or unsubstituted heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, or substituted or unsubstituted heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S;
- or alternatively, R2 and R3, together with the nitrogen atom to which they are attached, form a substituted or unsubstituted heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, or a substituted or unsubstituted heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S.
5 more elements
A compound of Formula (II), or a pharmaceutically acceptable salt thereof:
- wherein:
- R1 is unsubstituted C1-C6 alkyl;
- R4 and R5 are each, independently, H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted C3-C10 carbocycle, substituted or unsubstituted heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, or substituted or unsubstituted heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S;
- R6, R7, R8 and R9 are each, independently, H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl or C(O)ORa;
- and
- Ra is H or substituted or unsubstituted C1-C6 alkyl.
3 more elements
A compound of Formula (III), or a pharmaceutically acceptable salt thereof:
- wherein:
- R1 is unsubstituted C1-C6 alkyl;
- is selected from the group consisting of:
- X is N, O, S or SO2;
- Z is C or N;
- m is 0, 1, 2, or 3;
- n is 1 or 2;
- w is 0, 1, 2 or 3;
- t is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
- R6, R7, R8 and R9 are each, independently, H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl or C(O)ORa;
- and
- Ra is H or substituted or unsubstituted C1-C6 alkyl;
- and
- each R10 is, independently, H, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C3-C10 carbocycle, substituted or unsubstituted heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, or substituted or unsubstituted heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S;
- or, alternatively, two R10's attached to the same carbon atom, together with the carbon atom to which they are attached, form a carbonyl, substituted or unsubstituted C3-C10 carbocycle, substituted or unsubstituted heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, or substituted or unsubstituted heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S;
- or, alternatively, two R10's attached to different atoms, together with the atoms to which they are attached, form a substituted or unsubstituted C3-C10 carbocycle, substituted or unsubstituted heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, or substituted or unsubstituted heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S.
13 more elements
Dependencies are inferred from the claim text.