G.d. Searle & Company

Other

Pharmacia Corporation

Susan A Gregory

Gary D Anderson

Peter C Isakson

Richard A Mueller

John Patrick McKearn

Richard A Partis

Thomas E Barta

Francis J Koszyk

Kerry W Fowler

John M Farah, Jr

Peter G Isakson

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

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This invention is in the field of a combination comprising a therapeutically-effective amount of a cyclooxygenase-2 inhibitor, a 5-lipoxygenase inhibitor and an immunosuppressive drug selected from antiproliferative agents, antiinflammatory-acting compounds and inhibitors of leukocyte activation. This combination may be used, for example, to suppress the immune response associated with organ transplantation, graft versus host disease, and conditions with underlying autoimmune or inflammatory reactivities or responses.

Immunosuppressive effects of administration of a cyclooxygenase-2 inhibitor and a 5-lipoxygenase inhibitor

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

Immunosuppressive effects of administration of a cyclooxygenase-2 inhibitor, a leukotriene B4 receptor inhibitor and a cyclosporin

Treatment with a cyclooxygenase-2 inhibitor and a leukotriene A hydrolase inhibitor is described as being useful in reducing recipient rejection of transplanted organs and for treatment of autoimmnune diseases.

Immunosuppressive effects of administration of a cyclooxygenase-2 inhibitor and a leukotriene A4 hydrolase inhibitor

A method to suppress immune, acute or delayed-type hypersensitivity by treatment with a combination of a therapeutically-effective amount of a 5-lipoxygenase inhibitor and a cyclooxygenase-2 inhibitor is reported. The method may be used, for example, to suppress the immune response associated with organ transplantation, graft versus host disease, and conditions with underlying autoimmune or inflammatory reactivities or responses.

Combinations of a cyclooxygenase-2 inhibitor and a leukotriene B receptor antagonist are described for treatment of inflammation and inflammation-related disorders.

Treatment of inflammation and inflammation-related disorders with a combination of a cyclooxygenase-2 inhibitors and a leukotriene B4 receptor antagonist

A class of halogenated phenylacetonitrile alkylaminoalkylphenyl compounds having immunosuppressive properties is described. Compounds of this class would be useful in reducing recipient rejection of transplanted organs and for treatment of autoimmune or inflammatory diseases. Compounds of particular interest are of the formula

Halogenated phenylacetonitrile alkylaminoalkylphenyl compounds as immunosuppressives

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

Immunosuppressive effects of administration of a cyclooxygenase-2 inhibitor and a leukotriene B4 receptor antagonist

Combinations of a cyclooxygenase-2 inhibitor and a 5-lipoxygenase inhibitor are described for treatment of inflammation and inflammation-related disorders.

Treatment of inflammation and inflammation-related disorders with a

Combinations of a cyclooxygenase-2 inhibitor and a leukotriene A.sub.4 hydrolase inhibitor are described for treatment of inflammation and inflammation-related disorders.

A class of halogenated phenylacetonitrile alkylaminoalkylphenyl compounds having immunosuppressive properties is described. Compounds of this class would be useful in reducing recipient rejection of transplanted organs and for treatment of autoimmune or inflammatory diseases. Compounds of particular interest are of the formula ##STR1## wherein m is a number selected from three to five, inclusive; wherein n one or two; wherein R.sup.1 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, iso-butyl, n-pentyl, isopentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, benzyl and phenethyl; wherein R.sup.2 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, iso-butyl, n-pentyl, isopentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, benzyl and phenethyl; wherein each of R.sup.3 through R.sup.7 is selected from hydrido, fluoro, chloro, bromo, azide, trifluoromethyl, difluorochloromethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, perfluoroethyl and 2,2,2,3-tetrafluoropropyl; with the proviso that at least one of R.sup.3 through R.sup.7 is selected from fluoro and trifluoromethyl; or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

Halogenated phenylacetonitrile alkylaminoalkylphenyl compounds as

A class of substituted phenylacetonitrilehydroxyalkylaminoalkyl-ortho-substituted aryl compounds having immunosuppressive properties is described. Compounds of this class would be useful in reducing recipient rejection of transplanted organs and for treatment of autoimmune or inflammatory diseases. Compounds of particular interest are of the formula ##STR1## wherein each of m and n is a number independently selected from one to five, inclusive; wherein R.sup.1 is selected from hydrido, alkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, alkenyl and alkynyl; wherein R.sup.6 is selected from loweralkyl; wherein each of R.sup.8, R.sup.9, R.sup.10 and R.sup.12 through R.sup.16 is independently selected from hydrido, hydroxy, alkyl, hydroxyalkyl, alkoxy, alkenyl, alkynyl, alkylcarbonyl, alkoxycarbonyl, alkylcarbonylalkenyl, alkylaminocarbonyl and alkoxyalkyl; or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

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St. Louis, MO, United States of America

Susan A Gregory