Back to results
US 7,842,696 B2Granted
Piperazine derivatives as inhibitors of stearoyl-CoA desaturase
AssigneeForest Laboratories Holdings Limited
InventorsAlexander Bischoff, Hosahalli Subramanya, Kumar Sundaresan, Srinivasa Raju Sammeta, Anil Kumar Vaka
Life of this patent
Estimating the term…
Abstract
The present invention relates to piperazine derivatives that act as inhibitors of stearoyl-CoA desaturase. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
Claims53
A compound of formula (I):
- wherein
- R1 is halogenated alkyl;
- R2, R3, R4 and R5 are each independently hydrogen, halogen, hydroxy, cyano, nitro, amino, alkylamino, dialkylamino, carboxyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, aroyl, acyl, alkoxy, aryloxy, cycloalkyloxy, cycloalkylalkyloxy, arylalkyloxy, heteroarylalkyloxy, alkylhio, arylthio, alkylsulfinyl, alkylsulfonyl, alkoxycarbonyl, aryloxycarbonyl or heteroaryloxycarbonyl;
- R6 and R7 are each independently hydrogen, hydroxyl, cyano, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle or heterocyclealkyl;
- R8 is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle or heterocyclealkyl;
- R9 is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle or heterocyclealkyl;
- X is —C(O)—, —C(O)—O—, —S(O)2—, —S(O)—, or —C(O)NR10—, where R10 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle or heterocyclealkyl;
- Y is —C(O)—, —S(O)2—, or —S(O)—;
- wherein, when present, any aryl, heteroaryl, or heterocycle group may optionally be substituted by halogen, hydroxy, cyano, nitro, amino, alkylamino, dialkylamino, arylamino, diarylamino, amido, carboxyl, alkyl, halogenated alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, aroyl, acyl, alkoxy, aryloxy, heteroaryloxy, cycloalkyloxy, cycloalkylalkyloxy, arylalkyloxy, heteroarylalkyloxy, alkylhio, arylthio, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, heteroarylsulfinyl, heteroarylsulfonyl alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, arylalkyl-C(O)—, —C(O)O-alkyl, benzodioxol, benzo[d]oxazol-2(3H)-one, cycloalkyl-NH—C(O)—, and combinations thereof;
- or pharmaceutically acceptable salts thereof;
- with the proviso that said compound is not 4-chloro-N-[2-oxo-[4-[[2-(trifluoromethyl)phenyl]sulfonyl]-1-piperazinyl]ethyl]benzamide or a pharmaceutically acceptable salt thereof.
8 more elements
A compound of formula (II):
- wherein
- R11 is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle or heterocyclealkyl;
- R12 and R13 are each independently hydrogen, hydroxyl, cyano, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle or heterocyclealkyl;
- R15 is hydrogen or alkyl;
- A is —C(O)—, —S(O)2—, or —S(O)—;
- B is a bond, —C(O)—, —C(O)—O—, —S(O)2—, —S(O)—, or —C(O)NR15—, where R15 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle or heterocyclealkyl;
- R14 is aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle or heterocyclealkyl;
- wherein, when present, any aryl, heteroaryl, or heterocycle group may optionally be substituted by halogen, hydroxy, cyano, nitro, amino, alkylamino, dialkylamino, arylamino, diarylamino, amido, carboxyl, alkyl, halogenated alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, aroyl, acyl, alkoxy, aryloxy, heteroaryloxy, cycloalkyloxy, cycloalkylalkyloxy, arylalkyloxy, heteroarylalkyloxy, alkylhio, arylthio, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, heteroarylsulfinyl, heteroarylsulfonyl alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl and combinations thereof;
- or pharmaceutically acceptable salts thereof;
- with the proviso that when B is a bond, R14 is arylalkyl;
- and
- said compound is not
- N-[2-[4-(2-furanylcarbonyl)-1-piperazinyl]-2-oxoethyl]-[1,1′-biphenyl]-4-carboxamide,
- N-[2oxo-2-[4-(2-thienylcarbonyl)-1-piperazinyl]ethyl]-[1,1′-biphenyl]-4-carboxamide, or
- N-[1-methyl-2-oxo-2-[4-(phenylmethyl)-1-piperazinyl]ethyl]-[1,1′-biphenyl]-4-carboxamide,
- N-[2-[4-[(4-cyanophenyl)methyl]-1-piperazinyl]-2-oxoethyl]-[1,1′-biphenyl]-4-carboxamide,
- 2-[([1,1′-biphenyl]-4-ylmethyl)amino]3-phenyl-1-[4-(phenylmethyl)-1-piperazinyl]-1-propanone,
- or a pharmaceutically acceptable salt thereof.
15 more elements
A compound of formula (III):
- wherein
- R16 is hydrogen, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle or heterocyclealkyl;
- R17 is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle or heterocyclealkyl;
- R18 and R19 are each independently hydrogen, hydroxyl, cyano, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle or heterocyclealkyl;
- R20 is aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle or heterocyclealkyl;
- J is —C(O)—, —S(O)2—, or —S(O)—;
- G is a bond, —C(O)—, —C(O)—O—, —S(O)2—, —S(O)—, or —C(O)NR21—, where R21 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle or heterocyclealkyl;
- T is —O—, —S—, —NH—, —C(O)—, —S(O)— or —S(O)2—;
- wherein, when present, any aryl, heteroaryl, or heterocycle group may optionally be substituted by halogen, hydroxy, cyano, nitro, amino, alkylamino, dialkylamino, arylamino, diarylamino, amido, carboxyl, alkyl, halogenated alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, aroyl, acyl, alkoxy, aryloxy, heteroaryloxy, cycloalkyloxy, cycloalkylalkyloxy, arylalkyloxy, heteroarylalkyloxy, alkylhio, arylthio, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, heteroarylsulfinyl, heteroarylsulfonyl alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl and combinations thereof;
- or pharmaceutically acceptable salts thereof;
- with the proviso that when J is —C(O)—, R17-R19 are hydrogen and G is a bond, then R20 is not thienylmethyl, thiazolylmethyl, pyridinyl, thiazolylmethyl, pyrrolidinylethyl or pyridinylmethyl;
- and said compound is not
- N-[2-[4-(2-furanylcarbonyl)-1-piperazinyl]2-oxoethyl]-4-phenoxy-benzamide,
- N-[2-[4-[(3,5-dimethyl-4-isoxazolyl)sulfonyl]-1-piperazinyl]-2-oxoethyl]-4-phenoxy-benzamide,
- N-[(3,5-dimethyl-4-isoxazolyl)methoxy]-N-methyl-N-[2-oxo-2-[4-(phenylmethyl)-1-piperazinyl]ethyl]-benzamide,
- N2-oxo-2-[4-(2-thienylsulfonyl)-1-piperazinyl]ethyl]-4-phenoxy-benzamide,
- N-[2-oxo-2-[4-(2-thienylcarbonyl)-1-piperazinyl]ethyl]-4-phenoxy-benzamide, or
- N-methyl-N-[2-[4-[(3-methylphenyl)methyl]-1-piperazinyl]-2-oxoethyl]-4-(1-pyrrolidinylsulfonyl)-benzamide,
- N-[2-[4-(4-acetylphenyl)-1-piperazinyl]-2-oxoethyl]-4-phenoxy-benzamide,
- N-[2-[4-(4-methoxyphenyl)-1-piperazinyl]-2-oxoethyl]-4-phenoxy-benzamide,
- or a pharmaceutically acceptable salt thereof.
18 more elements
A compound of formula (IV):
- wherein
- R21 is halogen.
A compound of formula (V):
- Wherein
- R31 is halogenated alkyl;
- R32, R33, R34 and R35 are each independently hydrogen or halogen;
- R36 and R37 are each independently hydrogen or alkyl;
- R38 is hydrogen or alkyl;
- R39 is aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle or heterocyclealkyl;
- X1 is —C(O)—, —S(O)2—, or —S(O)—;
- Y1 is —C(R40)(R41)—, where R40 and R41 are each independently hydrogen or alkyl;
- wherein, when present, any aryl, heteroaryl, or heterocycle group may optionally be substituted by halogen, hydroxy, cyano, nitro, amino, alkylamino, dialkylamino, arylamino, diarylamino, amido, carboxyl, alkyl, halogenated alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, aroyl, acyl, alkoxy, aryloxy, heteroaryloxy, cycloalkyloxy, cycloalkylalkyloxy, arylalkyloxy, heteroarylalkyloxy, alkylhio, arylthio, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, heteroarylsulfinyl, heteroarylsulfonyl alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl and combinations thereof;
- or pharmaceutically acceptable salts thereof.
7 more elements
Dependencies are inferred from the claim text.