Combination therapy for treating obesity or maintaining weight loss

• US 20060270655A1
• Filed: 05/16/2006
• Published: 11/30/2006
• Est. Priority Date: 05/27/2005
• Status: Abandoned Application

• Current Assignee: Andrew G. Swick, Terrell A. Patterson
• Original Assignee: Andrew G. Swick, Terrell A. Patterson
• Inventors: Patterson, Terrell A., Swick, Andrew G.
• Application Number:
  US11/435,695
• Publication Number:
  US 20060270655A1
• Time in Patent Office: Days
• US Class Current: 514/210.210
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/4172 Imidazole-alkanecarboxylic acids, e.g. histidine
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/4741 condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Combination therapies for treating obesity or related eating disorders and/or reducing food consumption are described herein which comprises administering a therapeutically effective amount of a cannabinoid-1 (CB-1) receptor antagonist and an intestinal-acting microsomal triglyceride transfer protein inhibitor (MTPi) to an animal in need of such treatment. The CB-1 receptor antagonist and intestinal-acting MTPi may be administered separately or together.

Claims

1. A method for treating obesity and related eating disorders comprising the step of administering a therapeutically effective amount of a combination comprising a cannabinoid-1 receptor antagonist and an intestinal-acting microsomal triglyceride transfer protein inhibitor to an animal in need of such treatment.

3. The method of claim 1 or 2 wherein said cannabinoid-1 receptor antagonist is selected from the group consisting of

rimonabant;

N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-1H-pyrazole-3-carboxamide;

[5-(4-bromophenyl)-1-(2,4-dichloro-phenyl)-4-ethyl-N-(1-piperidinyl)-1H-pyrazole-3-carboxamide];

N-(piperidin-1-yl)-4,5-diphenyl-1-methylimidazole-2-carboxamide;

N-(piperidin-1-yl)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-1-methylimidazole-2-carboxamide;

N-(piperidin-1-yl)-4,5-di-(4-methylphenyl)-1-methylimidazole-2-carboxamide;

N-cyclohexyl-4,5-di-(4-methylphenyl)-1-methylimidazole-2-carboxamide;

N-(cyclohexyl)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-1-methylimidazole-2-carboxamide;

N-(phenyl)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-1-methylimidazole-2-carboxamide;

1-[9-(4-chloro-phenyl)-8-(2-chloro-phenyl)-9H-purin-6-yl]-4-ethylamino-piperidine-4-carboxylic acid amide, or a pharmaceutically acceptable salt thereof;

1-[7-(2-chloro-phenyl)-8-(4-chloro-phenyl)-2-methyl-pyrazolo[1,5-a][1,3,5]triazin-4-yl]-3-ethylamino-azetidine-3-carboxylic acid amide;

1-[7-(2-chloro-phenyl)-8-(4-chloro-phenyl)-2-methyl-pyrazolo[1,5-a][1,3,5]triazin-4-yl]-3-methylamino-azetidine-3-carboxylic acid amide;

3-(4-chloro-phenyl)-2-(2-chloro-phenyl)-6-(2,2-difluoro-propyl)-2,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one;

3-(4-chloro-phenyl)-2-(2-chloro-phenyl)-7-(2,2-difluoro-propyl)-6,7-dihydro-2H,5H4-oxa-1,2,7-triaza-azulen-8-one;

2-(2-chloro-phenyl)-6-(2,2,2-trifluoro-ethyl)-3-(4-trifluoromethyl-phenyl)-2,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one;

(S)₄-chloro-N-{[3-(4-chloro-phenyl)₄-phenyl-4,5-dihydro-pyrazol-1-yl]-methylamino-methylene}-benzenesulfonamide;

(S)-N-{[3-(4-chloro-phenyl)-4-phenyl-4,5-dihydro-pyrazol-1-yl]-methylamino-methylene}-4-trifluoromethyl-benzenesulfonamide;

N-piperidino-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethylpyrazole-3-carboxamide;

1-[bis-(4-chloro-phenyl)-methyl]-3-[(3,5-difluoro-phenyl)-methanesulfonyl-methylene]-azetidine;

2-(5-(trifluoromethyl)pyridin-2-yloxy)-N-(4-(4-chlorophenyl)-3-(3-cyanophenyl)butan-2-yl)-2-methylpropanamide;

4-{[6-methoxy-2-(4-methoxyphenyl)-1-benzofuran-3-yl]carbonyl}benzonitrile;

1-[2-(2,4-dichlorophenyl)-2-(4-fluorophenyl)-benzo[1,3]dioxole-5-sulfonyl]-piperidine; and

[3-amino-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)-furo[2,3-b]pyridin-2-yl]-phenyl-methanone;

or a pharmaceutically acceptable hydrate or solvate thereof.

4. The method of claim 1 or 2 wherein said intestinal-acting microsomal triglyceride transfer protein inhibitor is selected from the group consisting of

dirlotapide;

mitratapide;

1-methyl-5-[(4′

-trifluoromethyl-biphenyl-2-carbonyl)-amino]-1H-indole-2-carboxylic acid (carbamoyl-phenyl-methyl)-amide;

(S)-2-[(4′

-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-6-carboxylic acid (pentylcarbamoyl-phenyl-methyl)-amide;

(S)-2-[(4′

-tert-butyl-biphenyl-2-carbonyl)-amino]-quinoline-6-carboxylic acid {[(4-fluoro-benzyl)-methyl-carbamoyl]-phenyl-methyl}-amide;

(S)-2-[(4′

-tert-butyl-biphenyl-2-carbonyl)-amino]-quinoline-6-carboxylic acid [(4-fluoro-benzylcarbamoyl)-phenyl-methyl]-amide;

4-(4-(4-(4-((2-((4-methyl-4H-1,2,4-triazol-3-ylthio)methyl)-2-(4-chlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazin-1-yl)phenyl)-2-sec-butyl-2H-1,2,4-triazol-3(4H)-one; and

implitapide;

or a pharmaceutically acceptable hydrate or solvate thereof.

5. The method of claim 4 wherein said combination comprises from about 1.0 mg to about 100 mg of said cannabinoid-1 receptor antagonist.

6. The method of claim 4 wherein said combination comprises from about 0.05 mg to about 50 mg of intestinal-acting microsomal triglyceride transfer protein inhibitor.

7. The method of claim 1 or 2 wherein said cannabinoid-1 receptor antagonist and said intestinal-acting microsomal triglyceride transfer protein inhibitor are administered as a single pharmaceutical composition comprising said cannabinoid-1 receptor antagonist, said intestinal-acting microsomal triglyceride transfer protein inhibitor, and a pharmaceutically acceptable excipient, diluent, or carrier.

8. The method of claim 1 or 2 wherein said cannabinoid-1 receptor antagonist and said intestinal-acting microsomal triglyceride transfer protein inhibitor are administered as two separate pharmaceutical compositions comprising

(i) a first composition comprising said cannabinoid-1 receptor antagonist and a pharmaceutically acceptable excipient, diluent, or carrier, and

(ii) a second composition comprising said intestinal-acting microsomal triglyceride transfer protein inhibitor and a pharmaceutically acceptable excipient, diluent, or carrier.

2. A method for reducing food consumption comprising comprising the step of administering a therapeutically effective amount of a combination comprising a cannabinoid-1 receptor antagonist and an intestinal-acting microsomal triglyceride transfer protein inhibitor to an animal in need of such treatment.

9. A pharmaceutical composition (i) a CB-1 receptor antagonist;

(ii) a intestinal-acting MTPi; and

(iii) a pharmaceutically acceptable excipient, diluent, or carrier, wherein the amount of CB-1 receptor antagonist is from about 1.0 mg to about 100 mg and the amount of intestinal-acting MTPi is from about 0.05 mg to about 50 mg.