Quinolinyl ether or thioether tetrazoles as agents for the treat

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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Details

546152, A61K 3147, C07D26530, C07D29500

Patent

active

048747696

DESCRIPTION:

BRIEF SUMMARY
FIELD OF INVENTION

This invention relates to certain chemical compounds and their use as valuable pharmaceutical agents, particularly as lipoxygenase inhibitors and/or leukotriene antagonists possessing anti-inflammatory and anti-allergic properties.


SUMMARY OF THE INVENTION

This invention relates to the compounds described by the general Formula I and to therapeutic compositions comprising as active ingredient a compound of Formula I: ##STR1## where:
A is O or S;
B is --CR.sub.2 R.sub.3 --, O or S;
a is 0-2;
b is 0-1;
c is 0-2;
d is 0-5;
n is 0-2;
R is independently hydrogen, alkyl, hydroxy, alkoxy, carbalkoxy, halo, nitro, haloalkyl or cyano;
R.sub.1 and R.sub.2 are independently hydrogen, alkyl or aralkyl;
vicinal R.sub.2 groups together may form a carbon-carbon double-bond;
R.sub.3 is --(CH.sub.2).sub.x --X;
where x is 0-3 and
X is hydrogen, alkyl, alkenyl, cycloalkyl, aryl aralkyl, hydroxy, alkoxy, amino, mono- and di-alkylamino, aralkylamino, acylamino, carbamyl, carboxy or carbalkoxy;
vicinal R.sub.3 groups together may be --(CH.sub.2).sub.y --where y is 1-4, thus forming a 3-6 membered ring;
geminal R.sub.2 and R.sub.3 groups may together form a spiro substituent, --(CH.sub.2).sub.z --, where z is 2 to 5;
geminal R.sub.2 and R.sub.3 groups may together form an alkylidenyl substituent, ##STR2## where R.sub.4 is hydrogen or alkyl;
R' is hydrogen, alkyl or substituted alkyl where the substutuent may be carboxy, carbalkoxy, amino, mono- and di-alkylamino, aralkylamino, acylamino, carbamyl, mono- and di-alkyl carbamyl; and
pharmaceutically acceptable salts thereof.
Preferred compounds of this invention are described by Formulae II and III. ##STR3## where the substituents are as defined in Formula I.
More preferred compounds are those described by Formula II and III where:
A is O;
B is --CR.sub.2 R.sub.3 --, O, or S;
a is 1-2;
b is 0-1;
c is 0-1;
d is 0-4;
n is 0-1;
R is hydrogen, loweralkyl, hydroxy, loweralkoxy, carboloweralkoxy, halo, nitro, trifuloromethyl or cyano;
R.sub.1 and R.sub.2 are hydrogen or loweralkyl;
vicinal R.sub.2 groups together may form a carbon-carbon double bond;
R.sub.3 is --(CH.sub.2).sub.x --X
where x is 0-2 and
X is hydrogen, loweralkyl, cycloloweralkyl, phenyl, hydroxy, lower-alkoxy, amino, mono- and di-loweralkylamino, carbamyl, carboxy or carb-loweralkoxy;
vicinal R.sub.3 groups together may be --(CH.sub.2).sub.y -- where y is 2-4, thus forming a 4-6 membered ring;
geminal R.sub.2 and R.sub.3 groups may together form a spiro substituent, --(CH.sub.2).sub.z -- where is z 2 to 5;
geminal R.sub.2 and R.sub.3 groups may together form a loweralkylidenyl substituent, ##STR4## where R.sub.4 is hydrogen or loweralkyl;
R' is hydrogen, loweralkyl or substituted loweralkyl where the substituent may be carboxy, carb-loweralkoxy, amino, mono- and di-alkylamino, acetylamino, carbamyl, mono- and di-loweralkylcarbamyl; and
pharmaceutically acceptable salts thereof.
The most preferred compounds are those which form special embodiments by this invention and include those compounds described by Formulae IV and V: ##STR5## where:
c, d, R.sub.2 and R.sub.3 are as described above.
In addition, the present invention relates to the method of using these compounds as lipoxygenase inhibitors and/or leukotriene antagonists possessing anti-inflammatory and anti-allergic properties.
As employed above and throughout the disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings:
"Alkyl", either alone or with various substituents defined herein, means a saturated aliphatic hydrocarbon, either branched or straight chained. A "loweralkyl" is preferred having about 1 to about 6 carbon atoms. Examples of alkyl include methyl, ethyl, n-propyl, isopropyl, butyl, sec-butyl, t-butyl, amyl, hexyl, etc.
"Alkoxy" refers to a loweralkyl-O-group.
"Alkenyl" refers to a hydrocarbon having at least one point of unsaturation and may be branched or straight chained. Preferred alkenyl groups have six or less carbon atoms present such as vinyl, allyl, ethynyl, isoprope

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