Back to results
US 8,012,982 B2Granted
Modulators of HCV replication
AssigneeIstituto di Ricerche Biologia Molecolare P. Angeletti SpA
InventorsImmacolata Conte, Caterina Ercolani, Claudio Giuliano, Giovanni Migliaccio, Ian Stansfield
Life of this patent
Estimating the term…
Abstract
The present invention is directed to compounds of formula (I): where X, Y, R1, R2 and R3 are defined therein, which can act as modulators of viral replication and/or virus production, especially of the hepatitis C virus (HCV).
Claims7
The compound of formula (Ia) or a pharmaceutically acceptable salt thereof:
- wherein
- R4 is C1-6alkyl, C2-6alkenyl, C2-6alkynyl, (CH2)0-3C3-8cycloalkyl, C1-6alkoxy, (CH2)0-3aryl, (CH)2aryl, (C2)0-3Oaryl, (CH2)0-3heteroaryl and (CH2)0-3Oheteroaryl, optionally substituted by hydroxy, halogen, CN, CF3, C1-4alkyl, C1-4alkoxy, (CH2)0-3NR11C(O)OR12, (CH2)0-3aryl or (CH2)0-3heteroaryl,
- where R11 and R12 are each independently hydrogen or C1-6alkyl;
- and
- R15′ is CN, CF3, C2-4alkenyl, phenyl, OBn, C(O)C1-4alkyl, or C(O)phenyl.
2 more elements
A method of treating HCV infection by administering an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof:
- wherein
- X and Y are independently N;
- R1 is C(O)OR4, C(O)NR5R6, or C(O)R7;
- R2 is C(O)NR9R10 or NR9C(O)R10;
- R3 is absent or selected from halogen, hydroxy, C1-6alkyl and C1-6alkoxy;
- R5 and R9 are each independently hydrogen, C1-6alkyl or C3-8cycloalkyl;
- R4, R6, R7 and R8 are each independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, (CH2)0-3C3-8cycloalkyl, C1-6alkoxy, (CH2)0-3aryl, (CH)2aryl, (CH2)0-3Oaryl, (CH2)0-3heteroaryl and (CH2)0-3Oheteroaryl, optionally substituted by hydroxy, halogen, CN, CF3, C1-4alkyl, C1-4alkoxy, (CH2)0-3NR11C(O)OR12, (CH2)0-3aryl or (CH2)0-3heteroaryl,
- where R11 and R12 are each independently hydrogen or C1-6alkyl;
- R10 is (CH2)0-3aryl or (CH2)0-3heteroaryl, optionally substituted by halogen, CN, CF3, C1-4alkyl, C2-4alkenyl, OR13, C(O)R13, C(O)OR13, aryl, (CH)2aryl, (CH)2C(O)OR13 or NR13R14,
- where R13 and R14 are each independently hydrogen, C1-4alkyl or (CH2)0-3aryl,
- and where the optional substituent is further optionally substituted by hydroxy or halogen,
- and R10 may further be fused to a 5 - or 6-membered ring, which ring may be partially or fully unsaturated and which ring may contain one or two N atoms, said ring being optionally substituted by hydroxy, halogen, C1-4alkyl, C1-4alkoxy, C(O)R15 and C(O)OR15,
- where R15 is C1-4alkyl or aryl;
- with the proviso that the compound of formula (I) is not:
- tert-butyl4-(4-{[(4-hydroxyphenyl)amino]carbonyl}phenyl)piperazine-1-carboxylate,
- tert-butyl4-(4-{[(4-bromophenyl)amino]carbonyl}phenyl)piperazine-1-carboxylate,
- tert-butyl4-(4-{[(3-bromophenyl)amino]carbonyl}phenyl)piperazine-1-carboxylate,
- tert-butyl4-{4-[({3-[(1E)-3-methoxy-3-oxoprop-1-en-1-yl]phenyl}amino)carbonyl]phenyl}piperazine-1-carboxylate,
- tert-butyl4-{4-[(4-hydroxybenzoyl)amino]phenyl}piperazine-1-carboxylate, or
- tert-butyl4-{4-[(4-aminobenzoyl)amino]phenyl}piperazine-1-carboxylate.
17 more elements
A method of treating an illness due to hepatitis C virus, the method comprising administering to a human subject suffering from the illness a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof:
- wherein
- X and Y are independently N;
- R1 is C(O)OR4, C(O)NR5R6, or C(O)R7;
- R2 is C(O)NR9R10 or NR9C(O)R10;
- R3 is absent or selected from halogen, hydroxy, C1-6alkyl and C1-6alkoxy;
- R5 and R9 are each independently hydrogen, C1-6alkyl or C3-8cycloalkyl;
- R4, R6, R7 and R8 are each independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, (CH2)0-3 C3-8cycloalkyl, C1-6alkoxy, (CH2)0-3aryl, (CH)2aryl, (CH2)0-3Oaryl, (CH2)0-3heteroaryl and (CH2)0-3Oheteroaryl, optionally substituted by hydroxy, halogen, CN, CF3, C1-4alkyl, C1-4alkoxy, (CH2)0-3NR11C(O)OR12, (CH2)0-3 aryl or (CH2)0-3heteroaryl,
- where R11 and R12 are each independently hydrogen or C1-6alkyl;
- R10 is (CH2)0-3aryl or (CH2)0-3heteroaryl, optionally substituted by halogen, CN, CF3, C1-4alkyl, C2-4alkenyl, OR13, C(O)R13, C(O)OR13, aryl, (CH)2aryl, (CH)2C(O)OR13 or NR13R14,
- where R13 and R14 are each independently hydrogen, C1-4alkyl or (CH2)0-3aryl,
- and where the optional substituent is further optionally substituted by hydroxy or halogen,
- and R10 may further be fused to a 5- or 6-membered ring, which ring may be partially or fully unsaturated and which ring may contain one or two N atoms, said ring being optionally substituted by hydroxy, halogen, C1-4alkyl, C1-4alkoxy, C(O)R15 and C(O)OR15,
- where R15 is C1-4alkyl or aryl, with the proviso that the compound of formula (I) is not:
- tent-butyl4-(4-{[(4-hydroxyphenyl)amino]carbonyl}phenyl)piperazine-1-carboxylate,
- tert-butyl4-(4-{[(4-bromophenyl)amino]carbonyl}phenyl)piperazine-1-carboxylate,
- tent-butyl4-(4-{[(3-bromophenyl)amino]carbonyl}phenyl)piperazine-1-carboxylate,
- tent-butyl4- {4- [({3-[(1E)-3-methoxy-3-oxoprop-1-en-1-yl]phenyl}amino)carbonyl]phenyl}piperazine-1-carboxylate,
- tert-butyl4-{4-[(4-hydroxybenzoyl)amino]phenyl}piperazine-1-carboxylate, or
- tert-butyl4-{4-[(4-aminobenzoyl)amino]phenyl}piperazine-1-carboxylate.
16 more elements
Dependencies are inferred from the claim text.