Immunosuppressive effects of administration of a cyclooxygenase-2 inhibitor, a leukotriene B4receptor inhibitor and a cyclosporin

• US 7,141,599 B2
• Filed: 07/10/2003
• Issued: 11/28/2006
• Est. Priority Date: 02/13/1996
• Status: Expired due to Fees

• Current Assignee: Pharmacia Corporation (Pfizer Inc.)
• Original Assignee: Pharmacia Corporation (Pfizer Inc.)
• Inventors: Isakson, Peter G., Gregory, Susan A, Anderson, Gary
• Primary Examiner(s): Low, Christopher S. F.
• Assistant Examiner(s): KWON, BRIAN YONG S
• Application Number:
  US10/617,222
• Publication Number:
  US 20040106668A1
• Time in Patent Office: 1,237 Days
• Field of Search: 514/395, 514/406
• US Class Current: 514/395
• 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 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/10 Sulfides; Sulfoxides; Sulfones
• CPC Class Codes: A61K 31/18 Sulfonamides compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/02 Local antiseptics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 : Antianaemics

Abstract

Treatment with a cyclooxygenase-2 inhibitor and a leukotriene B₄ receptor antagonist is described as being useful in reducing recipient rejection of transplanted organs and for treatment of autoimmune diseases.

Claims

1. A composition comprising an immunosuppressive

3. The composition of claim 1 wherein the leukotriene B4 receptor antagonist is selected from the group consisting of 3-[2-[[3-(5-hydroxy-1,5-dimethyl-hexyl)-3a-methyl-1,2,3,3a,4,5,6,7a-octahydroinden-7-ylidene]]ethylidene]-2-methylene-cyclohexane-1,5-diol, 2-Benzoxazolamine, N-[(1 S)-2-cyclohexyl-1 -(2-pyridinyl)ethy]-5-methyl- (9C1), Benzeneacetic acid, cyclopentyl-4-(2-quinolinylmethoxy), Benzamide, 4-[[5-[4-(aminoiminomethyl)phenoxy]pentyl]oxy]-3-methoxy-N,N-bis(1-methylethyl)-,(2Z)-2-butenedioate (1:

1 ) (9Cl), 1,2 -Benzisoselenazol-3(2H)-one, 2-phenyl- (9Cl), Benzoic acid, 4-[[[(3-fluorophenyl)methyl][4-(2-quinolinylmethoxy)phenyl]amino]methyl]- (9Cl), Benzoic acid, 2-[3-[3-[(5-ethyl-4′

-fluoro-2-hydroxyl1,1′

-biphenyl]-4-yl)oxy]propoxy]-2-propylphenoxy]- (9Cl), Benzenepropanoic acid, 2-(4-carboxybutoxy)-6-[[(5E)-6-(4-methoxyphenyl)-5-hexenyl]oxy]- (9Cl), Carbonic acid, 4-[5-[[2-[4-(diphenylmethoxyl)-1-piperidinyl]ethyl]amino]-5-oxo-1,3-pentadienyl]-2-methoxyphenyl ethyl ester (9Cl), 2-Benzoxazolamine, N-[(1S)-2-cyclohexyl-1-(2-pyridinyl)ethyl]-5-methyl- (9Cl), Benzenepropanoic acid, 5-(3-carboxybenzoyl)-2-(decyloxy)- (9Cl), 9H-Xanthene-4-propanoic acid, 7-carboxy-3-(decyloxy)-9-oxo- (9Cl), 9H-Xanthene-4-propanoic acid, 7-carboxy-3-[3-[(5-ethyl-4′

-fluoro-2-hydroxy[1,1′

-biphenyl]-4-yl)oxy]propoxy]-9-oxo- (9Cl), Benzenepropanoic acid, 2-(4-carboxybutoxy)-6-[[(5E)-6-(4-methoxyphenyl)-5-hexenyl]oxy]- (9Cl), Cyclopentanecarboxylic acid, 1-[(3S,4R)-3-([1,1′

-biphenyl]-4-ylmethyl)-3,4-dihydro-4-hydroxy-2H-1-benzopyran-7-yl]- (9Cl), Pyrrolidine, 1-[5-hydroxy-5-[8-(1-hydroxy-2-phenylethyl)-2-dibenzofuranyl]-1-oxopentyl]- (9Cl), 2-Thiopheneheptanoic acid, dimethyl-3-(3-phenylpropyl)- (9Cl), 2-Propenoic acid, 3-[6-[[(3-aminophenyl)sulfinyl]methyl]-3-[[8-(4-methoxyphenyl)octyl]oxy]-2-pyridinyl]-, (2E)- (9Cl), Benzoic acid, 3-[[[[6-[(1E)-2-carboxyethenyl]-5-[[8-(4-methoxyhenyl)octyl]oxy]-2-pyridinyl]methyl]thio]methyl]- (9Cl), 2-Propenoic acid, 3-[6-[[(2,6-dichlorophenyl)thio]methyl]-3-(2-phenylethoxy)-2-pyridinyl]-, (2E)- (9Cl), 2H-1-Benzopyran-2-propanoic acid, 7-[3-[2-(cyclopropylmethyl)-3-methoxy-4-[(methylamino)carbonyl]phenoxy]propoxy]-3,4-dihydro-8-propyl-, (2S)-(9Cl), 2H-1-Benzopyran-2-carboxylic acid, 7-[3-[2-(cyclopropylmethyl)-3-methoxy-4-(4-thiazolyl) phenoxy]propoxy]-3,4-dihydro-8-propyl-, (+)- (9Cl), β

-Alanine, N-[[6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]-2-pyridinyl]carbonyl]-N-ethyl- (9Cl), [1,1′

-Biphenyl]-4-acetic acid, 2-fluoro-4′

-(2-quinolinylmethoxy)-(9Cl).

2. A composition comprising an immunosuppressive

4. The composition of claim 2 wherein the leukotriene B4 receptor antagonist is selected from the group consisting of 3-[2-[[3-(5-hydroxy-1,5-dimethyl-hexyl)-3a-methyl-1,2,3,3a,4,5,6,7a-octahydroinden-7-ylidene]]ethylidene]-2-methylene-cyclohexane-1,5-diol, 2-Benzoxazolamine, N-[(1S)-2-cyclohexyl-1-(2-pyridinyl)ethyl]-5-methyl- (9Cl), Benzeneacetic acid, cyclopentyl-4-(2-quinolinyimethoxy), Benzamide, 4-[[5-[4-(aminoiminomethyl)phenoxy]pentyl]oxy]-3-methoxy-N,N-bis(1-methylethyl)-, (2Z)-2-butenedioate (1:

1) (9Cl), 1,2-Benzisoselenazol-3(2H)-one, 2-phenyl- (9Cl), Benzoic acid, 4-[[[(3-fluorophenyl)methyl][4-(2-quinolinylmethoxy)phenyl]amino]methyl]- (9Cl), Benzoic acid, 2-[3-[3-[(5-ethyl-4′

-fluoro-2-hydroxy[1,1′

-biphenyl]-4-yl)oxy]propoxy]-2-propylphenoxy]- (9Cl), Benzenepropanoic acid, 2-(4-carboxybutoxy)-6-[[(5E)-6-(4-methoxyphenyl)-5-hexenyl]oxy]- (9Cl), Carbonic acid, 4-[5-[[2-[4-(diphenylmethoxy)-1-piperidinyl]ethyl]amino]-5-oxo-1,3-pentadienyl]-2-methoxyphenyl ethyl ester (9Cl), 2-Benzoxazolamine, N-[(1S)-2-cyclohexyl-1-(2-pyridinyl) ethyl]-5-methyl- (9Cl), Benzenepropanoic acid, 5-(3-carboxy benzoyl)-2-(decyloxy)- (9Cl), 9H-Xanthene-4-propanoic acid, 7-carboxy-3-(decyloxy)-9-oxo- (9Cl), 9H-Xanthene-4-propanoic acid, 7-carboxy-3-[3-[(5-ethyl-4′

-fluoro-2-hydroxy[1,1′

-biphenyl]-4-yl)oxy]propoxyl-9-oxo- (9Cl), Benzenepropanoic acid, 2-(4-carboxybutoxy)-6-[[(5E) -6-(4-methoxyphenyl)-5-hexenyl]oxy]- (9Cl), Cyclopentanecarboxylic acid, 1-[(3S,4R)-3-([1,1-biphenyl]-4-ylmethyl)-3,4-dihydro-4-hydroxy-2H-1 -benzopyran-7-yl]-(9Cl)., Pyrrolidine, 1-[5-hydroxy-5-[8-(1-hydroxy-2-phenylethyl)-2-dibenzofuranyl]-1-oxopentyl]- (9Cl), 2-Thiopheneheptanoic acid, dimethyl-3-(3-phenylpropyl)- (9Cl), 2-Propenoic acid, 3-[6-[[(3-aminophenyl)sulfinyl]methyl]-3-[[8-(4-methoxyphenyl)octyl]oxy]-2-pyridinyl-, (2E)- (9Cl), Benzoic acid, 3-[[[[6-[(1E)-2-carboxyethenyl]-5-[[8-(4-methoxyphenyl)octyl]oxy]-2-pyridinyl]methyl]thio] methyl]- (9Cl), 2-Propenoic acid, 3-[6-[[(2,6-dichlorophenyl)thio]methyl]-3-(2-phenylethoxy)-2-pyridinyl]-, (2E)- (9Cl), 2H-1 -Benzopyran-2-propanoic acid, 7-[3-[2-(cyclopropylmethyl)-3-methoxy-4-[(methylamino)carbonyl]phenoxy]propoxy]-3,4-dihydro-8-propyl-, (2S)- (9Cl), 2H-1 -Benzopyran-2-carboxylic acid, 7-[3-[2-(cyclopropylmethyl)-3-methoxy-4-(4-thiazolyl)phenoxy]propoxy]-3,4-dihydro-8-propyl-, (+)- (9Cl), β

-Alanine, N-[[6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy) methyl]-2-pyridinyl]carbonyl]-N-ethyl- (9Cl), and [1,1′

-Biphenyl]-4-acetic acid, 2-fluoro-4′

-(2-quinolinylmethoxy)-(9Cl).