US 2010/0305121 A1 · NOVEL ANTAGONISTS OF THE HUMAN FATTY ACID SYNTHASE THIOESTERASE

Abstract

The present invention provides for compounds of formula (I)-(XIII), as well as pharmaceutically acceptable salts thereof, metabolites thereof, pro-drugs thereof, and pharmaceutical kits that include such compounds. The present invention also provides for the compounds of formula (I)-(XIII) for use in medical therapy or diagnosis. The present invention also provides for the use of the compounds of formula (I)-(XIII) in treating cancer in mammals (e.g., humans), as well inhibiting tumor cell growth in such mammals. The present invention also provides for methods of inhibiting FAS. The methods include contacting FAS with an effective amount of a compound of formula (I)-(XIII). The present invention also provides for methods of inhibiting the TE domain of the FAS. The methods include contacting the thioesterase TE domain of the FAS with an effective amount of a compound of formula (I)-(XIII). The present invention also provides for methods of treating cancer in mammals, as well as methods of inhibiting tumor cell growth in such mammals. The methods include administering a compound of formula (I)-(XIII) to a mammal in need of such treatment.

Claims32

Dependent claims

A compound having formula (I):

or a pharmaceutically acceptable salt or solvate thereof, wherein:
X1, X2, and X3 are each independently O, S, or NOH;
R1 and R2 are each independently hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, aryl, alkylaryl, heteroaryl, heterocycle, or cycloalkyl;
R3, R4, R5, R6, and R7 are each independently hydrogen, alkyl, alkenyl, alkoxy, halogen, haloalkyl, hydroxyl, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, imino, alkylamino, acylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, NRxRy or COORx, wherein each Rx and Ry is independently hydrogen, alkyl, alkenyl, aryl, heteroaryl, heterocycle, cycloalkyl or hydroxyl, and
wherein each of the groups for R1, R2, R3, R4, R5, R6, and R7, may optionally be independently substituted with one or more alkyl, alkenyl, alkylidenyl, alkenylidenyl, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, imino, alkylamino, acylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, acetamido, acetoxy, acetyl, benzamido, benzenesulfinyl, benzenesulfonamido, benzenesulfonyl, benzenesulfonylamino, benzoyl, benzoylamino, benzoyloxy, benzyl, benzyloxy, benzyloxycarbonyl, benzylthio, carbamoyl, isocyannato, sulfamoyl, sulfinamoyl, sulfino, sulfo, sulfoamino, thiosulfo, NRxRy and/or COORx groups, wherein each of Rx and Ry are independently hydrogen, alkyl, alkenyl, aryl, heteroaryl, heterocycle, cycloalkyl or hydroxyl.

2 more elements

Dependencies are inferred from the claim text.

Novel antagonists of the human fatty acid synthase thioesterase

Life of this patent

Novel antagonists of the human fatty acid synthase thioesterase

Life of this patent

Abstract

Claims32