Substituted tetralins, chromans and related compounds in the treatment of asthma, arthritis and related diseases
AssigneePfizer Inc.
InventorsJames F. Eggler, Anthony Marfat, Lawrence S. Melvin, Jr.
Life of this patent
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Abstract
Substituted tetralins, chromans and related compounds which, by inhibiting 5-lipoxygenase enzyme and/or blocking leukotriene receptors, are useful in the prevention or treatment of asthma, arthritis, psoriasis, ulcers, myocardial infarction and related disease states in mammals, pharmaceutical compositions thereof, a method of treatment therewith, and to intermediates useful in the synthesis thereof.
Claims35
A racemic or optically active compound having the structural formual ##STR10## wherein n is 0 or 1;
- m is 0 or an integer from 1 to 3;
- X is CH.sub.2, O, S, SO, SO.sub.2, NH or N(C.sub.1 -C.sub.4)alkyl;
- X.sup.1 is CH.sub.2, O, S, SO or SO.sub.2 ;
- Y and Y.sup.1 are taken together and form a carbonyl group, or Y and Y.sup.1 are taken separately, Y is hydrogen and Y.sup.1 is hydroxy or an acyloxy group which is hydrolyzed to form a hydroxy group under physiological conditions;
- Z is CH.sub.2, CHCH.sub.3, CH.sub.2 CH.sub.2 or CH.sub.2 CH.sub.2 CH.sub.2 ;
- Z.sup.1 is CH or N;
- R is 2-, 3-, 4 or 8-quinolyl, or one of said groups mono- or disubstituted on carbon with the same or different substituents which are bromo, chloro, fluoro, (C.sub.1 -C.sub.4)alkyl, trifluoromethyl, hydroxy, hydroxymethyl or (C.sub.1 -C.sub.4)alkoxy, or on adjacent carbons with trimethylene, tetramethylene, --CH.sub.2 --O--CH.sub.2 -- or --O--CH.sub.2 --O--;
- and
- R.sup.1 is attached by means of aromatic or heteroaromatic carbon and is phenyl, naphthyl, pyridyl, pyridazinyl, pyrymidinyl, pyrrolyl, N-[(C.sub.1 -C.sub.4) alkyl]pyrrolyl, pyrazolyl, 1-[(C.sub.1 -C.sub.4)alkyl]pyrazolyl, imidazolyl, 1-[(C.sub.1 -C.sub.4)alkyl]imidazolyl, furyl, oxazolyl, isoxazolyl, thienyl, thiazolyl, isothiazolyl;
- or, only when either X.sup.1 is CH.sub.2 or m is at least 2, R.sup.1 is attached by means of hetrocyclic nitrogen and is 1-pyrrolyl, 1-pyrazolyl, or 1-imidazolyl;
- or R.sup.1 is one of said groups which is mono- or disubstituted on carbon with the same or different groups which are bromo, chloro, fluoro, hydroxy, hydroxymethyl, CF.sub.3, (C.sub.1 -C.sub.4)alkyl, (C.sub.1 -C.sub.4)alkoxy, carboxy, [(C.sub.1 -C.sub.4)alkoxy]carbonyl, or substituted on adjacent carbons with trimethylene, tetramethylene, --CH.sub.2 --O--CH.sub.2 -- or --O--CH.sub.2 --O--;
- or substituted on tertiary nitrogen to form an N-oxide;
- a pharmaceutically acceptable acid addition salt thereof;
- or
- a pharmaceutically acceptable cationic salt when the compound contains a carboxy group.
A compound of calim 15 wherein X and X.sup.1 are each O, R is 6-fluoro-2-quinolyl and R.sup.1 is 4-methoxyphenyl.
A method of claim 34 wherein the mammal is suffering from arthritis, said compound administered to prevent or relieve the symptoms of said arthritis.
Dependencies are inferred from the claim text.