Fat accumulation-modulation compounds
AssigneeAdipoGenix, Inc.
InventorsMichael John Stevenson, Harrison Jefferson Leighton
Life of this patent
Estimating the term…
Abstract
The present invention pertains to compounds effective at modulating fatty acid or triglyceride (“fat”) accumulation by cells, such compounds having therapeutic potential as regulators of body mass and for the treatment of overweight individuals, obesity, and metabolic disorders. Featured compounds are set forth and exemplified herein. Therapeutic methods and pharmaceutical compositions featuring these compounds are also provided.
Claims141
A method of modulating the accumulation of a fatty acid or triglyceride in a cell, comprising a step of contacting said cell with a compound, wherein said compound comprises a substituted or unsubstituted aryl group and an amide, sulfonamide, or ureylene group, such that modulation of said fatty acid or triglyceride accumulation occurs.
The method according to any one of the foregoing claims, wherein modulation of said fatty acid or triglyceride uptake is a means of treating or preventing a disease or condition in a subject.
The method according to any one of the foregoing claims, wherein R1 is a naphthyl group or an Ar group, wherein said Ar group is selected from the group consisting of
- 82
- p is an integer from zero to five inclusive,
- X is selected from the group consisting of a substituted or unsubstituted straight or branched alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted carbocyclic, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryloxyalkyl, substituted or unsubstituted arylacetamidoyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heteroaralkyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted arylcarbonyl, substituted or unsubstituted heteroarylcarbonoyl, or substituted or unsubstituted heteroaryl group;
- or
- (CR′R″)1-12H, (CR′R″)0-3NR′R″, (CR′R″)0-3CN, (CR′R″)0-3NO2, halogen, (CR′R″)0-3C(halogen)3, (CR′R″)0-3CH(halogen)2, (CR′R″)0-3CH2(halogen), (CR′R″)0-3CONR′R″, (CR′R″)0-3S(O)1-2NR′R″, (CR′R″)0-3CHO, (CR′R″)0-3O(CR′R″)0-3H, (CR′R″)0-3S(O)0-2R′, (CR′R″)0-3O(CR′R″)0-3H, (CR′R″)0-3COR′, (CR′R″)0-3CO2R′, and (CR′R″)0-3OR′;
- wherein each of R′ and R″ is independently hydrogen, a C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, aryl-(C1-C5 alkyl), or aryl group, or R′ and R″ taken together are a benzylidene group or a —(CH2)nO(CH2)n— (wherein each n is 1, 2, or 3) group.
The method according to any one of the foregoing claims, wherein L is a linking group of less than about 250 molecular weight.
The method according to any one of the foregoing claims, wherein said R group is a substituted or unsubstituted branched, bicyclic, cyclic, or unbranched C1-C20 alkyl group or a substituted or unsubstituted branched, bicyclic, cyclic, or unbranched C2-C20 alkylene group.
The method according to any one of the foregoing claims, wherein said R group is an iso-propyl, methyl, iso-butyl, 2-benzylideneheptyl, sec-butyl, cyclohexyl, cyclopropyl, 2-(N-morpholinyl)-ethyl, a sec-phenylethyl or phenylethyl group.
The method according to any one of the foregoing claims, wherein said R group is
- 85
- wherein each m is an integer from 1 to 8 inclusive, and each n is an integer from 0 to 5 inclusive.
The method according to any one of the foregoing claims, wherein said R group is
- 86
- wherein Q is a halogen, hydrogen, or a C1-C5 alkyl, O(C1-C5 alkyl), or benzyloxy group.
The method according to any one of the foregoing claims, wherein said R group is a cyclopropyl or cyclohexyl group.
The method according to any one of the foregoing claims, wherein said R group is
- 87
- wherein n is an integer from 1 to 3 inclusive, and Q is a C1-C5 alkyl, C2-C5 alkenyl, or C2-C5 alkynyl group.
The method according to any one of the foregoing claims, wherein said R group is
- 88
- wherein n is an integer from 0 to 5 inclusive, and Q is a C1-C5 alkyl, O(C1-C5 alkyl), or benzyloxy group, or Q is a halogen, and E is a direct bond or an oxygen atom.
The method according to any one of the foregoing claims, wherein said R group is a benzoyl,
- 89
The method according to any one of the foregoing claims, wherein said R group is
- 90
- wherein Q is NH, O, or S, and n is an integer from 0 to 6.
The method according to any one of the foregoing claims, wherein said R group is
- 91
- wherein m is an integer from 0 to 3, and n is an integer from 1 to 7.
The method according to any one of the foregoing claims, wherein said R group is (CR′R″)0-3CH(phenyl)2;
- wherein R′ and R″ are each independently hydrogen, a C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl.
The method according to any one of the foregoing claims, wherein said R group is a naphthyl group, or a partially hydrogenated derivative thereof.
The method according to any one of the foregoing claims, wherein said R group is
- 92
- wherein n is an integer from 1 to 4.
The method according to any one of the foregoing claims, wherein said R group is
- 95
- wherein
- n is an integer from zero to six inclusive,
- p is an integer from zero to five inclusive,
- X is selected from the group consisting of a substituted or unsubstituted straight or branched alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted carbocyclic, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryloxyalkyl, substituted or unsubstituted arylacetamidoyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heteroaralkyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted arylcarbonyl, substituted or unsubstituted heteroarylcarbonoyl, or substituted or unsubstituted heteroaryl group;
- or
- (CR′R″)1-12H, (CR′R″)0-3NR′R″, (CR′R″)0-3CN, (CR′R″)0-3NO2, halogen, (CR′R″)0-3C(halogen)3, (CR′R″)0-3CH(halogen)2, (CR′R″)0-3CH2(halogen), (CR′R″)0-3CONR′R″, (CR′R″)0-3S(O)1-2NR′R″, (CR′R″)0-3CHO, (CR′R″)0-3O(CR′R″)0-3H, (CR′R″)0-3S(O)0-2R′, (CR′R″)0-3O(CR′R″)0-3H, (CR′R″)0-3COR′, (CR′R″)0-3CO2R′, and (CR′R″)0-3OR′;
- wherein each of R′ and R″ is independently hydrogen, a C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, aryl-(C1-C5 alkyl), or aryl group, or R′ and R″ taken together are a benzylidene group or a —(CH2)nO(CH2)n— (wherein each n is 1, 2, or 3) group.
The method according to any one of the foregoing claims, wherein said R group is
- 96
- wherein
- n is an integer from zero to six inclusive.
The method of modulating the accumulation of a fatty acid or triglyceride according to any claim herein, wherein the said compound is selected from those depicted in the accompanying Drawings, and, pharmacautically acceptable salts thereof.
A pharmaceutical composition for use in the method of any claim herein.
A prodrug pharmaceutical composition for use in the method of any claim herein.
The method of any one of the preceding claims, wherein said compound is administered with a suitable pharmaceutical carrier.
A pharmaceutical composition comprising an effective amount of a compound of any of the preceding claims in combination with a second agent.
The pharmaceutical composition of any one of the foregoing claims, wherein said pharmaceutical composition further comprises a pharmaceutically acceptable carrier.
A packaged composition for treatment of a disease or condition with any compound according to any of the foregoing claims, comprising said compound and directions for using said compound for treating said disease according to said method.
An animal feedstock comprising a chemical according to any Formula herein.
Dependencies are inferred from the claim text.