Back to results
US 2008/0200461 A1Published application
Modulators of acetyl-coenzyme a carboxylase and methods of use thereof
AssigneeCropsolution, Inc.
InventorsRichard Anderson, Takeo Hokama, Shy-Fuh Lee, Rafael Oey, Tedd Elich, Steven Breazeale
Life of this patent
Estimating the term…
Abstract
The present invention provides compounds of formula I: along with methods of use thereof for the control of agricultural pests, particularly fungal pests, weedy pests and insect pests, as well as use as pharmaceuticals, particularly the treatment of obesity, metabolic syndrome, atherosclerosis, cardiovascular disease and insulin resistance, e.g., type II or adult-onset diabetes as well as fungal pathogens of humans and animals
Claims40
A compound of formula I:
- wherein
- R1 and R2 are taken independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, COR6, COOR6, CONR7R8, SO2NR7R8, SO2R9, alkoxyalkyl, alkylthioalkyl, aryl, arylalkyl or aryloxyalkyl optionally substituted with halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, cyano, acyl, alkylsulfinyl, alkylsulfonyl, alkylene, haloalkylene, alkylenedioxy, haloalkylenedioxy, and NO2,
- or R1 and R2 may together to form a 5- or 6-membered ring comprised of 3 to 5 carbon atoms, 1 to 2 nitrogen atoms, 0 to 1 oxygen atom, and 0 to 1 sulfur atom, optionally substituted by halogen, alkyl, haloalkyl, alkoxyalkyl, haloalkoxyalkyl, arylalkyl, ═O, ═S, and optionally fused to another 5- or 6-membered ring;
- R3 and R4 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, CH2COR6, CH2COOR6, CH2CONR7R8, O, aryl, arylalkyl or heteroarylalkyl optionally substituted with halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, cyano, acyl, alkylsulfinyl, alkylsulfonyl, alkylene, haloalkylene, alkylenedioxy, haloalkylenedioxy, and NO2,
- or R3 and R4 may together to form a 5- or 6-membered ring comprised of 3 to 5 carbon atoms, 1 to 2 nitrogen atoms, 0 to 1 oxygen atom, and 0 to 1 sulfur atom, optionally substituted by halogen, alkyl, haloalkyl, alkoxyalkyl, haloalkoxyalkyl, arylalkyl, ═O, ═S, and optionally fused to another 5- or 6-membered ring;
- R5 can be a non-bonded pair of electrons or is selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl;
- arylalkyl or heteroarylalkyl optionally substituted with halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, cyano, acyl, alkylsulfinyl, alkylsulfonyl, alkylene, haloalkylene, alkylenedioxy, haloalkylenedioxy, and NO2;
- when R5 is alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, arylalkyl or heteroarylalkyl optionally substituted with halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, cyano, acyl, alkylsulfinyl, alkylsulfonyl, alkylene, haloalkylene, alkylenedioxy, haloalkylenedioxy, or NO2, the N-atom to which R3, R4, and R5 are attached will carry a positive charge and be associated with anion Y−, where Y may be halogen, carboxylate, sulfonate or any other suitable counterion;
- R6, R7, R8 and R9 are each independently selected from the group consisting of H, alkyl, haloalkyl, alkoxyalkyl, haloalkoxyalkyl, alkylthioalkyl, haloalkylthioalkyl, aryl or arylalkyl optionally substituted with halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, CN, aryl, arylalkyl, aryloxy, arylalkoxy, arylalkylthio, alkylene, haloalkylene, alkylenedioxy, haloalkylenedioxy, wherein said aryl, arylalkyl, aryloxy, arylalkoxy, arylalkylthio is optionally substituted with independently selected halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy;
- X is a bridge consisting of 2 to 8 carbon atoms, 0 to 1 nitrogen atom, 0 to 1 oxygen atom, and 0 to 1 sulfur atom optionally substituted with halogen, alkyl, haloalkyl, hydroxy, alkoxy, haloalkoxy, alkylthio, cyano, acyl, alkylsulfinyl, alkylsulfonyl, or NO2
- n is 1 or 2;
- or a salt thereof.
9 more elements
A pharmaceutical combination composition comprising in combination:
- a therapeutically effective amount of a composition comprising a first compound, said first compound being a formula I compound, a prodrug thereof, or a pharmaceutically acceptable salt of said compound or of said prodrug;
- a second compound, said second compound being an anti-atherosclerosis agent, an anti-diabetic agent, an anti-obesity agent or a cardiovascular agent and/or optionally a pharmaceutically acceptable vehicle, diluent or carrier.
A method of making a compound of formula I:
- wherein
- R1 and R2 are taken independently from H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, COR6, COOR6, CONR7R8, SO2NR7R8, SO2R9, alkoxyalkyl, alkylthioalkyl, aryl, arylalkyl or aryloxyalkyl optionally substituted with halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, cyano, acyl, alkylsulfinyl, alkylsulfonyl, alkylene, haloalkylene, alkylenedioxy, haloalkylenedioxy, or NO2,
- or R1 and R2 may be taken together to form a 5- or 6-membered ring comprised of 3 to 5 carbon atoms, 1 to 2 nitrogen atoms, 0 to 1 oxygen atom, and 0 to 1 sulfur atom, optionally substituted by halogen, alkyl, haloalkyl, alkoxyalkyl, haloalkoxyalkyl, arylalkyl, ═O, ═S, and optionally fused to another 5- or 6-membered ring;
- R3 and R4 are taken separately from alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, CH2COR6, CH2COOR6, CH2CONR7R8, O, aryl, arylalkyl or heteroarylalkyl optionally substituted with halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, cyano, acyl, alkylsulfinyl, alkylsulfonyl, alkylene, haloalkylene, alkylenedioxy, haloalkylenedioxy, or NO2,
- or R3 and R4 may be taken together to form a 5- or 6-membered ring comprised of 3 to 5 carbon atoms, 1 to 2 nitrogen atoms, 0 to 1 oxygen atom, and 0 to 1 sulfur atom, optionally substituted by halogen, alkyl, haloalkyl, alkoxyalkyl, haloalkoxyalkyl, arylalkyl, ═(O)n, ═S, and optionally fused to another 5- or 6-membered ring;
- R5 may be a non-bonded pair of electrons, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, arylalkyl or heteroarylalkyl optionally substituted with halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, cyano, acyl, alkylsulfinyl, alkylsulfonyl, alkylene, haloalkylene, alkylenedioxy, haloalkylenedioxy, or NO2;
- when R5 is alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, arylalkyl or heteroarylalkyl optionally substituted with halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, cyano, acyl, alkylsulfinyl, alkylsulfonyl, alkylene, haloalkylene, alkylenedioxy, haloalkylenedioxy, or NO2, the N-atom to which R3, R4, and R5 are attached will carry a positive charge and be associated with anion Y−, where Y may be halogen, carboxylate, sulfonate or any other suitable counterion;
- R6, R7, R8 and R9 are each independently selected from the group consisting of H, alkyl, haloalkyl, alkoxyalkyl, haloalkoxyalkyl, alkylthioalkyl, haloalkylthioalkyl, aryl or arylalkyl optionally substituted with halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, CN, aryl, arylalkyl, aryloxy, arylalkoxy, arylalkylthio, alkylene, haloalkylene, alkylenedioxy, haloalkylenedioxy, or wherein said aryl, arylalkyl, aryloxy, arylalkoxy, arylalkylthio is optionally substituted with independently selected halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy;
- X is a bridge group consisting of 2 to 8 C-atoms, 0 to 1 N-atom, 0 to 1 O-atom and 0 to 1 S-atom optionally substituted with halogen, alkyl, haloalkyl, hydroxy, alkoxy, haloalkoxy, alkylthio, cyano, acyl, alkylsulfinyl, alkylsulfonyl, or NO2
- n is 1 or 2;
- comprising:
- alkylation of an amine II with an appropriate halide (Q=Cl, Br, or I) in an inert solvent.
9 more elements
A method of making a compound of formula I:
- wherein
- R1 and R2 are taken independently from H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, COR6, COOR6, CONR7R8, SO2NR7R8, SO2R9, alkoxyalkyl, alkylthioalkyl, aryl, arylalkyl or aryloxyalkyl optionally substituted with halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, cyano, acyl, alkylsulfinyl, alkylsulfonyl, alkylene, haloalkylene, alkylenedioxy, haloalkylenedioxy, or NO2,
- or R1 and R2 may be taken together to form a 5- or 6-membered ring comprised of 3 to 5 carbon atoms, 1 to 2 nitrogen atoms, 0 to 1 oxygen atom, and 0 to 1 sulfur atom, optionally substituted by halogen, alkyl, haloalkyl, alkoxyalkyl, haloalkoxyalkyl, arylalkyl, ═O, ═S, and optionally fused to another 5- or 6-membered ring;
- R3 and R4 are taken separately from alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, CH2COR6, CH2COOR6, CH2CONR7R8, aryl, arylalkyl or heteroarylalkyl optionally substituted with halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, cyano, acyl, alkylsulfinyl, alkylsulfonyl, alkylene, haloalkylene, alkylenedioxy, haloalkylenedioxy, or NO2,
- or R3 and R4 may be taken together to form a 5- or 6-membered ring comprised of 3 to 5 carbon atoms, 1 to 2 nitrogen atoms, 0 to 1 oxygen atom, and 0 to 1 sulfur atom, optionally substituted by halogen, alkyl, haloalkyl, alkoxyalkyl, haloalkoxyalkyl, arylalkyl, ═(O)n, ═S, and optionally fused to another 5- or 6-membered ring;
- R5 may be a non-bonded pair of electrons, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, arylalkyl or heteroarylalkyl optionally substituted with halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, cyano, acyl, alkylsulfinyl, alkylsulfonyl, alkylene, haloalkylene, alkylenedioxy, haloalkylenedioxy, or NO2;
- when R5 is alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl;
- arylalkyl or heteroarylalkyl optionally substituted with halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, cyano, acyl, alkylsulfinyl, alkylsulfonyl, alkylene, haloalkylene, alkylenedioxy, haloalkylenedioxy, or NO2, the N-atom to which R3, R4, and R5 are attached will carry a positive charge and be associated with anion Y−, where Y may be halogen, carboxylate, sulfonate or any other suitable counterion;
- R6, R7, R8 and R9 are each independently selected from the group consisting of H, alkyl, haloalkyl, alkoxyalkyl, haloalkoxyalkyl, alkylthioalkyl, haloalkylthioalkyl, aryl or arylalkyl optionally substituted with halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, CN, aryl, arylalkyl, aryloxy, arylalkoxy, arylalkylthio wherein said aryl, arylalkyl, aryloxy, arylalkoxy, arylalkylthio, alkylene, haloalkylene, alkylenedioxy, haloalkylenedioxy is optionally substituted with independently selected halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy;
- X is a bridge group consisting of 2 to 8 C-atoms, 0 to 1 N-atom, 0 to 1 O-atom and 0 to 1 S-atom optionally substituted with halogen, alkyl, haloalkyl, hydroxy, alkoxy, haloalkoxy, alkylthio, cyano, acyl, alkylsulfinyl, alkylsulfonyl, or NO2
- n is 1 or 2;
- comprising:
- alkylation of an amine II with a sulfonate ester (Q=OSO2R′) III in an inert solvent.
10 more elements
Dependencies are inferred from the claim text.