INHIBITORS OF FATTY ACID AMIDE HYDROLASE

• US 20110172186A1
• Filed: 10/08/2010
• Published: 07/14/2011
• Est. Priority Date: 04/09/2008
• Status: Active Grant

• Current Assignee: Infinity Pharmaceuticals, Inc.
• Original Assignee: Infinity Pharmaceuticals, Inc.
• Inventors: Behnke, Mark L., Grogan, Michael J., Tibbitts, Thomas T., Snyder, Daniel A., Castro, Alfredo C., Liu, Tao, Evans, Catherine A., Grenier, Louis
• Granted Patent: US 8,957,049 B2
• Time in Patent Office: Days
• US Class Current: 514/64
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 : Antidepressants
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 27/06 : Antiglaucoma agents or miotics
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07F 5/02 : Boron compounds
• CPC Class Codes: C07F 5/025 : Boronic and borinic acid compounds

Abstract

The present invention provides compounds, and pharmaceutically acceptable compositions thereof, encompassed by any of formulae (I), (II), (III), (IV), (V), or (VI), or subgenera thereof. The present invention also provides methods for treating an FAAH mediated disease, disorder or condition by administering a therapeutically effective amount of a compound or composition comprising a compound of any of formulae (I), (II), (III), (IV), (V), or (VI), or subgenera thereof, to a patient in need thereof. Additionally, the present invention provides methods for inhibiting FAAH by administering a therapeutically effective amount of a compound or composition comprising a compound of any of formulae (I), (II), (III), (IV), (V), or (VI), or subgenera thereof, to a patient in need thereof.

Claims

1-73. -73. (canceled)

74. A compound of the following formula:

75. The compound of claim 74, wherein W³ is C or CR¹⁵.

76. The compound of claim 74, wherein W³ is N.

77. The compound of claim 74, wherein X is a covalent bond, —

O—

, —

(CH═

CH)—

or —

(CH₂)—

.

78. The compound of claim 74, wherein Z¹ and Z² are both OH.

79. The compound of claim 78, wherein n is 0.

80. The compound of claim 79, wherein R² is optionally substituted C_1-8 alkyl.

81. The compound of claim 80, wherein the C_1-8 alkyl is substituted with optionally substituted phenyl.

82. The compound of claim 80, wherein the C_1-8 alkyl is substituted with —

CF₃ or —

CF₂CF₃.

83. The compound of claim 80, wherein the C_1-8 alkyl is substituted with an optionally substituted 5- or 6-membered ring having 0-4 heteroatoms selected from N, O or S.

84. The compound of claim 80, wherein the C_1-8 alkyl is substituted with) —

N(R⁰)C(O)OR⁰, wherein each R⁰ is independently hydrogen or C_1-8 alkyl.

85. The compound of claim 79, wherein R² is optionally substituted C_6-10 aryl or optionally substituted 5 to 10 membered heteroaryl.

86. The compound of claim 74, wherein n is 1.

87. The compound of claim 86, wherein R¹ is a halogen or —

CF₃.

88. The compound of claim 86, wherein R² is optionally substituted C_6-10 aryl.

89. The compound of claim 74, which is:

90. A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt or prodrug thereof, of claim 74, and a pharmaceutically acceptable excipient, medium, or carrier.

91. A method of treating an FAAH-mediated disease, disorder or condition comprising administering to a patient a therapeutically effective amount of a compound of claim 74, or a pharmaceutically acceptable composition thereof.

92. The method of claim 91, wherein the FAAH-mediated disease, disorder or condition is painful condition, disease or disorder, inflammatory disorders, immune disorders, depression, anxiety, anxiety-related disorders, sleep disorders, feeding behaviors, movement disorders, glaucoma, neuroprotection or cardiovascular disease.