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US 2010/0075931 A1Published application
Substituted oxazole ketone modulators of fatty acid amide hydrolase
AssigneeThe Scripps Research Institute
InventorDale L. Boger
Life of this patent
Estimating the term…
Abstract
Certain oxazole ketone compounds are described, which are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity. Thus, the compounds may be administered to treat, e.g., anxiety, pain, inflammation, sleep disorders, eating disorders, or movement disorders (such as multiple sclerosis).
Claims25
A chemical entity selected from compounds of Formula (I):
- wherein:
- n is 0, 1, 2, or 3;
- R1 is —CF3;
- —CN;
- —CHO;
- —C(O)C1-4alkyl unsubstituted or substituted with one, two, or three fluoro substituents;
- —CO2C1-4alkyl;
- —CO2H;
- —C(O)N(Ra)Rb;
- —CH2NRaRb;
- —SO2N(Rc)Rd;
- —SC1-4alkyl;
- —SO2C1-4alkyl;
- —SO2CF3;
- or halo;
- where Ra and Rb are each independently —H, —C1-6alkyl, or —C3-6cycloalkyl, or Ra and Rb taken together with the nitrogen to which they are attached form a saturated monocyclic heterocycloalkyl group, unsubstituted or substituted with —C1-4alkyl, —OH, —OC1-4alkyl, or halo;
- and
- Rc and Rd are each independently —H or —C1-6alkyl;
- and
- R2 is —H;
- —C1-6alkyl;
- —C3-6cycloalkyl;
- —CF3;
- —CN;
- —C(O)C1-4alkyl optionally substituted with one, two, or three fluoro substituents;
- —CO2C1-4alkyl;
- —CO2H;
- —C(O)N(Rf)Rg;
- —OH;
- —OC1-6alkyl;
- halo;
- —NO2;
- —NRfRg;
- —N(Rf)CORg;
- —N(Rf)SO2Rg;
- —SO2N(Rf)R9;
- or
- —S(O)0-2Rh;
- where Rf and Rg are each independently —H, —C1-6alkyl, or —C3-6cycloalkyl;
- and
- Rh is —C1-4alkyl unsubstituted or substituted with one, two, or three fluoro substituents;
- and pharmaceutically acceptable salts of compounds of Formula (I),
- pharmaceutically acceptable prodrugs of compounds of Formula (I), and
- pharmaceutically active metabolites of Formula (I).
41 more elements
A chemical entity selected from the group consisting of:
- Methyl 2-(7-phenylheptanoyl)oxazole-5-carboxylate;
- 2-(7-Phenylheptanoyl)oxazole-5-carboxylic acid;
- 2-(7-Phenylheptanoyl)oxazole-5-carboxamide;
- 1-(5-(Morpholine-4-carbonyl)oxazol-2-yl)-7-phenylheptan-1-one;
- 7-Phenyl-1-(5-(piperidine-1-carbonyl)oxazol-2-yl)heptan-1-one;
- 7-Phenyl-1-(5-(thiomorpholine-4-carbonyl)oxazol-2-yl)heptan-1-one;
- 1-(5-(4-Methylpiperazine-1-carbonyl)oxazol-2-yl)-7-phenylheptan-1-one;
- N-Methyl-2-(7-phenylheptanoyl)oxazole-5-carboxamide;
- N,N-Dimethyl-2-(7-phenylheptanoyl)oxazole-5-carboxamide;
- 1-(5-Acetyloxazol-2-yl)-7-phenylheptan-1-one;
- 7-Phenyl-1-(5-(2,2,2-trifluoroacetyl)oxazol-2-yl)heptan-1-one;
- 2-(7-Phenylheptanoyl)oxazole-5-carbaldehyde;
- 2-(7-Phenylheptanoyl)oxazole-5-carbonitrile;
- 1-(5-Methyloxazol-2-yl)-7-phenylheptan-1-one;
- 7-Phenyl-1-(5-(trifluoromethyl)oxazol-2-yl)heptan-1-one;
- 1-(5-Iodooxazol-2-yl)-7-phenylheptan-1-one;
- 1-(5-Bromooxazol-2-yl)-7-phenylheptan-1-one;
- 1-(5-Chlorooxazol-2-yl)-7-phenylheptan-1-one;
- 1-(5-Fluorooxazol-2-yl)-7-phenylheptan-1-one;
- 1-(5-(Methylthio)oxazol-2-yl)-7-phenylheptan-1-one;
- 1-(5-(Methylsulfonyl)oxazol-2-yl)-7-phenylheptan-1-one;
- 7-Phenyl-1-(5-(trifluoromethylsulfonyl)oxazol-2-yl)heptan-1-one;
- 7-(3-Methoxyphenyl)-1-(oxazol-2-yl)heptan-1-one;
- 7-(3-Methoxy-phenyl)-1-(5-trifluoromethyl-oxazol-2-yl)-heptan-1-one;
- 7-(3-Fluoro-phenyl)-1-(5-methanesulfonyl-oxazol-2-yl)-heptan-1-one;
- 2-[7-(3-Methanesulfonyl-phenyl)-heptanoyl]-oxazole-5-carboxylic acid;
- 4-[7-(5-Carbamoyl-oxazol-2-yl)-7-oxo-heptyl]-benzoic acid;
- and
- 3-[7-(5-Dimethylcarbamoyl-oxazol-2-yl)-7-oxo-heptyl]-benzoic acid methyl ester;
- and pharmaceutically acceptable salts thereof.
27 more elements
A pharmaceutical composition for treating a disease, disorder, or medical condition mediated by FAAH activity, comprising:
- (a) an effective amount of at least one chemical entity selected from compounds of Formula (I):
- wherein:
- n is 0, 1, 2, or 3;
- R1 is —CF3;
- —CN;
- —CHO;
- —C(O)C1-4alkyl unsubstituted or substituted with one, two, or three fluoro substituents;
- —CO2C1-4alkyl;
- —CO2H;
- —C(O)N(Ra)Rb;
- —CH2NRaRb;
- —SO2N(Rc)Rd;
- —SC1-4alkyl;
- —SO2C1-4alkyl;
- —SO2CF3;
- or halo;
- where Ra and Rb are each independently —H, —C1-6alkyl, or —C3-6cycloalkyl, or Ra and Rb taken together with the nitrogen to which they are attached form a saturated monocyclic heterocycloalkyl group, unsubstituted or substituted with —C1-4alkyl, —OH, —C1-4alkyl, or halo;
- and
- Rc and Rd are each independently —H or —C1-6alkyl;
- and
- R2 is —H;
- —C1-6alkyl;
- —C3-6cycloalkyl;
- —CF3;
- —CN;
- —C(O)C1-4alkyl optionally substituted with one, two, or three fluoro substituents;
- —CO2C1-4alkyl;
- —CO2H;
- —C(O)N(Rf)Rg;
- —OH;
- —OC1-6alkyl;
- halo;
- —NO2;
- —NRfRg;
- —N(Rf)CORg;
- —N(Rf)SO2Rg;
- —SO2N(Rf)Rg;
- or
- —S(O)0-2Rh;
- where Rf and Rg are each independently —H, —C1-6alkyl or —C3-6cycloalkyl;
- and
- Rh is —C1-4alkyl unsubstituted or substituted with one, two, or three fluoro substituents;
- and pharmaceutically acceptable salts of Formula (I), pharmaceutically acceptable prodrugs of Formula (I), and pharmaceutically active metabolites of Formula (I);
- and
- (b) a pharmaceutically acceptable excipient.
42 more elements
A method of treating a subject suffering from or diagnosed with a disease, disorder, or medical condition mediated by FAAH activity, comprising administering to the subject in need of such treatment an effective amount of at least one chemical entity selected from compounds of Formula (I):
- wherein:
- n is 0, 1, 2, or 3;
- R1 is —CF3;
- —CN;
- —CHO;
- —C(O)C1-4alkyl unsubstituted or substituted with one, two, or three fluoro substituents;
- —CO2C1-4alkyl;
- —CO2H;
- —C(O)N(Ra)Rb;
- —CH2NRaRb;
- —SO2N(Rc)Rd;
- —SC1-4alkyl;
- —SO2C1-4alkyl;
- —SO2CF3;
- or halo;
- where Ra and Rb are each independently —H, —C1-6alkyl, or —C3-6cycloalkyl, or Ra and Rb taken together with the nitrogen to which they are attached form a saturated monocyclic heterocycloalkyl group, unsubstituted or substituted with —C1-4alkyl, —OH, —OC1-4alkyl, or halo;
- and
- Rc and Rd are each independently —H or —C1-6alkyl;
- and
- R2 is H;
- —C1-6alkyl;
- —C3-6cycloalkyl;
- —CF3;
- —CN;
- —C(O)C1-4alkyl optionally substituted with one, two, or three fluoro substituents;
- —CO2C1-4alkyl;
- —CO2H;
- —C(O)N(Rf)Rg;
- —OH;
- —OC1-6alkyl;
- halo;
- —NO2;
- —NRfRg;
- —N(Rf)CORg;
- —N(Rf)SO2Rg;
- —SO2N(Rf)Rg;
- or
- —S(O)0-2Rh;
- where Rf and Rg are each independently —H, —C1-6alkyl, or —C3-6cycloalkyl;
- and
- Rh is —C1-4alkyl unsubstituted or substituted with one, two, or three fluoro substituents;
- and pharmaceutically acceptable salts of Formula (I), pharmaceutically acceptable prodrugs of Formula (I), and pharmaceutically active metabolites of Formula (I).
39 more elements
Dependencies are inferred from the claim text.