Inhibition of 5-lipoxygenase products
AssigneeSmithKline Beckman Corporation
InventorsPaul E. Bender, Don E. Griswold, Nabil Hanna, Henry M. Sarau
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Abstract
Novel compounds, compositions and pharmaceutical a method of inhibiting the 5-lipoxygenase pathway in an animal in need thereof which comprising administering an effective, 5-lipoxygenase pathway inhibiting amount of a 4,5-diaryl-2(substituted)-imidazole or a pharmaceutically acceptable salt thereof.
Claims37
A compound of the formula ##STR32## wherein:
- X.sup.1 is NHCN or NH.sub.2 ;
- R.sup.1 and R are independently selected from 4-pyridyl or monosubstituted phenyl wherein said substituent is selected from halo or C.sub.1-4 alkoxy;
- and
- Y.sup.1 is H or CN provided that when X.sup.1 is NH.sub.2, Y.sup.1 is CN when X.sup.1 is NHCN, Y.sup.1 is H;
- or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition having 5-lipoxygenase inhibitory activity comprising an effective, non-toxic 5-lipoxygenase pathway inhibiting amount of a compound of the formula ##STR33## wherein:
- X.sup.1 is NHCN or NH.sub.2 ;
- R.sup.1 and R are independently selected from 4-pyridyl or monosubstituted phenyl wherein said substituent is selected from halo or C.sub.1-4 alkoxy;
- and
- Y.sup.1 is H or CN provided that when X.sup.1 is NH.sub.2, Y.sup.1 is CN and when X.sup.1 is NHCN, Y.sup.1 is H;
- or a pharmaceutically acceptable salt or thereof, and a pharmaceutically acceptable carrier or diluent.
A method for treating rheumatoid arthritis in an animal in need thereof which comprises administering to such animal an effective, non-toxic 5-lipoxygenase pathway inhibiting amount of a compound of the formula ##STR34## wherein:
- X.sup.1 is NHCN or NH.sub.2 ;
- R.sup.1 and R are independently selected from 4-pyridyl or monosubstituted phenyl wherein said substituent is selected from halo or C.sub.1-4 alkoxy;
- and
- Y.sup.1 is H or CN provided that when X.sup.1 is NH.sub.2, Y.sup.1 is CN and when X.sup.1 is NHCN, Y.sup.1 is H;
- or a pharmaceutically acceptable salt thereof.
A method of treating a 5-lipoxygenase pathway mediated disease in an animal in need thereof, provided that such animal is in need of treatment of a 5-lipoxygenase pathway mediated disease other than, or in addition to, rheumatoid arthritis, which comprises administering to such animal an effective, non-toxic 5-lipoxygenase pathway inhibiting amount of a compound of the formula, ##STR35## wherein:
- X is S, S(0).sub.n R.sup.2, NHCN, NH.sub.2, polyhalo C.sub.1-4 alkyl, or 4-halophenyl;
- n is 0, 1 or 2;
- R.sup.2 is selected from H, C.sub.1-6 alkyl, or mono- or polyhalo C.sub.1-4 alkyl;
- R and R.sup.1 are independently selected from pyridyl or mono substituted phenyl wherein said substituent is selected from halo or C.sub.1-4 alkoxy;
- provided that when R and/or R.sup.1 are pyridyl, R.sup.2 is other than C.sub.1-6 alkyl, tetrahaloethyl or C.sub.1-4 perhaloalkyl;
- and
- Y is H, CN, or C.sub.1-4 alkyl provided that when X is NH.sub.2, Y is CN and when X is NHCN, Y is H;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.