Back to results
US 5,686,434 AGranted
3-aryl-2-isoxazolines as antiinflammatory agents
AssigneePfizer Inc.
InventorEdward Fox Kleinman
Life of this patent
Estimating the term…
Abstract
This invention relates to 3-aryl-2-isoxazoline compounds which are selective inhibitors of phosphodiesterase type IV (PDE.sub.IV). The 3-aryl-2-isoxazolines are useful in the treatment of AIDS, asthma, arthritis, bronchitis, chronic obstructive pulmonary disease, psoriasis, allergic rhinitis, dermatitis, shock, atopic dermatitis, rheumatoid arthritis and osteoarthritis. This invention also relates to pharmaceutical compositions useful therefor.
Claims16
A compound of the formula ##STR28## the racemic, racemic-diastereomeric mixtures and optical isomers of said compound and the pharmaceutically acceptable salts thereof wherein
- Y.sup.1 is --OR.sup.1 and is attached to the 4-position of the phenyl ring and Y.sup.2 is --OR.sup.2 and is attached to the 3-position of the phenyl ring;
- R.sup.1 is alkyl having 1 to 3 carbons, fluoromethyl, difluoromethyl or trifluoromethyl;
- R.sup.2 is (C.sub.3 -C.sub.7)cycloalkyl, optionally substituted phenylalkyl having 1 to 6 carbons in the alkyl portion or bicycloalkyl having 6 to 9 carbons;
- wherein the aromatic portion of the optionally substituted phenylalkyl is optionally independently substituted with (C.sub.1 -C.sub.4) alkyl, (C.sub.1 -C.sub.4) alkoxy, halogen or CF.sub.3 ;
- R.sup.3 is hydrogen, (C.sub.1 -C.sub.3)alkyl, mono-hydroxyalkyl having 1 to 3 carbons or alkoxyalkyl having 1 to 3 carbons in the alkyl portion and 1 to 3 carbons in the alkoxy portion;
- R.sup.4 is hydrogen, (C.sub.1 -C.sub.5)alkyl, --COOH, alkoxyalkyl having 1 to 3 carbons in the alkyl portion and 1 to 3 carbons in the alkoxy portion, N-alkylaminoalkyl having 1 to 3 carbons in the alkylamino portion and 1 to 3 carbons in the alkyl portion or N,N-dialkylaminoalkyl having a total of 2 to 6 carbons in the dialkylamino portion and 1 to 3 carbons in the alkyl portion;
- or R.sup.3 and R.sup.4 are taken together with the carbon atoms to which they are attached and form --CH.sub.2 OCH.sub.2 OCH.sub.2 --;
- and
- R.sup.5 is hydrogen, --CHO, amino, aminoalkyl having 1 to 3 carbons, ##STR29## mono-hydroxyalkyl having 1 to 3 carbons, --(CH.sub.2).sub.b --COOR.sup.6, --COR.sup.7, --(CH.sub.2).sub.m CO.sub.2 H, (C.sub.1 -C.sub.4) alkyl, hydroxy, --(CH.sub.2).sub.q CONX.sup.2 X.sup.3, --(CH.sub.2).sub.r SO.sub.2 NX.sup.4 X.sup.5, --(CH.sub.2).sub.s PO.sub.3 H.sub.2 or ##STR30## wherein b is 0 or an integer from 1 to 6;
- m, n, q, r, s and t are independently 0, 1, 2, 3 or 4;
- R.sup.6 and R.sup.7 are each independently (C.sub.1 -C.sub.4)alkyl;
- X.sup.1 is hydrogen, (C.sub.1 -C.sub.4) alkyl, --O(C.sub.1 -C.sub.4) alkyl or alkoxyphenyl having one to four carbon atoms in the alkoxy portion;
- X.sup.2, X.sup.3, X.sup.4 and X.sup.5 are each independently hydrogen or (C.sub.1 -C.sub.3) alkyl;
- and
- X.sup.6 is (C.sub.1 -C.sub.3)alkyl or phenyl;
- provided that when R.sup.4 is --COOH then R.sup.5 is not --COOH.
13 more elements
Dependencies are inferred from the claim text.