E. R. Squibb Sons, Inc.

Squibb & Sons, Inc.

Gordon, Eric M.

Haslanger, Martin F.

Varma, Ravi K.

Karanewksy, Donald S.

Hall, Steven E.

Ravi K Varma

Eric M Gordon

Christopher M Cimarusti

Sam T Chao

B Richard Vogt

Martin F Haslanger

Frank L Weisenborn

Jack Bernstein

Jagabandhu Das

Steven E Hall

Donald S Karanewsky

Paul Grabowich

Jeffrey O Saunders

Rudiger D Haugwitz

Dinos P Santafianos

Ligaya M Simpkins

Carl P Ciosek

Donald S Karanewksy

##STR1## and pharmaceutically acceptable salts thereof possess activity as cell-selective HMG-CoA reductase inhibitors, thus making them useful as antihypercholesterolemic agents. In the above formula,

Sulfur-substituted mevinic acid derivatives

Compounds of the formula ##STR1## and pharmaceutically acceptable salts thereof have been found to possess activity as cell-selective HMG-CoA reductase inhibitors, thus making them useful as antihypercholesterolemic agents. In the above formula, ##STR2## R.sup.1 is hydrogen, alkyl, cycloalkyl, aryl or arylalkyl; and R.sup.2 is hydrogen, alkyl, ammonium, or alkali metal.

6-.alpha.-hydroxy derivatives of mevinic acids

Compounds of the formula ##STR1## and pharmaceutically acceptable salts and tautomeric mixtures thereof possess activity as HMg-CoA reductase inhibitors, thus making them useful as antihypercholesterolemic agents. In the above formula,

Fluorinated derivatives of mevinic acids

Antihypercholesterolemic activity is exhibited by novel compounds of the formula ##STR1## wherein: Z is ##STR2## X is lower alkyl or lower alenyl; R.sup.1 is aryl or alkyl;

1-aroyl or 1-acyl-2-2pyrrolidinyl-3,5-dihydroxy alkanoic and alkenoic

Antihypercholesterolemic activity has been discovered in compounds of the formula ##STR1## and pharmaceutically acceptable salts thereof, wherein: Z is ##STR2## X is lower alkyl, lower alkenyl, or lower alkenyl; R.sup.1 is hydrogen, alkyl, alkenyl, aryl, alkylaryl, or substituted aryl having one or more substituents; and

2-pyrrolidone substituted dihydroxy alkanoic, alkenoic and alkynoic

Phenyl hydroxamic acids are disclosed having the general formula ##STR1## or a pharmaceutically acceptable salt thereof, wherein X is NR, oxygen, sulfur, ##STR2## or a single bond, and Y is NR, oxygen, sulfur, ##STR3## or a single bond, where R can be hydrogen or lower alkyl, g can be 1 or 2, and with the proviso that at least one of X and Y is other than a single bond; Z is aryl, aralkyl or cycloalkyl; R.sub.1 is hydrogen, substituted or unsubstituted lower alkyl, cycloalkyl, lower alkenyl or aryl; R.sub.2 is hydrogen, lower alkyl, aroyl or acyl; m is 0 to 4 carbon atoms; and, n is 0 to 4 carbon atoms further providing that if one of X or Y is oxygen, the other of X or Y must be oxygen and further that when X and Y are oxygen Z cannot be aralalkyl. These new compounds have been found to be inhibitors or arachidonic acid 5-lipoxygenase and are therefore useful as antiallergy agents and antipsoriatics.

Phenyl hydroxamic acids including a hetero-containing substituent

Arylhydroxamates are provided having the structure ##STR1## wherein R.sup.1 is hydrogen, lower alkyl, aryl, lower alkenyl, cycloalkyl, or aralkyl;

Arylhydroxamates and use thereof in treating allergies

Biphenyl hydroxamic acids are provided having the structure ##STR1## wherein m is 1 to 7, X is S, O or NH, R is H, lower alkyl, aryl, aralkyl or cycloalkyl and R.sup.1 is H, lower alkyl, aryl, aralkyl, cycloalkyl, alkanoyl or aroyl. These compounds are inhibitors of .DELTA..sup.5 -lipoxygenase and as such are useful as antiallergy agents.

Biphenyl hydroxamic acids

Certain arylalkyl or pyridylalkyl hydroxamates useful for treating

7-Oxabicyclo(2.2.1)heptane analogs are disclosed having the general formula ##STR1## wherein R.sub.1 is lower alkyl, alkenyl, substituted alkenyl or alkynyl; R.sub.2 is lower alkyl, alkenyl or alkynyl; A is --CH.sub.2 --CH.dbd.CH-- or a single bond; X is --CH.sub.2, --CH(CH.sub.3) or --C(CH.sub.3).sub.2 ; n is an integer from 0 to 9, with the proviso that when A is a single bond, n is an integer from 1 to 9; including all stereoisomers. These new compounds have been found to be inhibitors of arachidonic acid cyclooxygenase and are therefore useful as antiinflammatory antipyretic and analgesic agents.

7-oxabicyclo(2.2.1)heptane compounds useful in the treatment of

A compound of the formula ##STR1## wherein R.sub.1 is hydrogen, hydroxy, alkoxy or aryloxy; R.sub.2 is hydrogen, hydroxy, alkoxy or aryloxy; or wherein R.sub.1 and R.sub.2 taken together is an aromatic ring; R.sub.3 is hydrogen or lower alkyl; R.sub.4 is lower alkyl, substituted alkyl, alkenyl or alkynyl; X is amino, alkylamino, alkanoylamino, oxygen or a single bond; A is CH.sub.2 --CH.dbd.CH or a single bond; and n is an integer from 0 to 9, with the proviso that when A is a single bond, n is an integer from 1 to 9 including all stereoisomers thereof. These new compounds have been found to simultaneously inhibit the arachidonic acid enzymes 5-lipoxygenase and cyclooxygenase and as such are useful, for example, as antiinflammatory agents.

7-oxabicyclo(2.2.1)heptane analogs useful as inhibitors of

7-Oxabicyclo(2.2.1)heptane-based N-hydroxy-N-alkyl (or aryl) ureas, carbamic acids and carbamothioic acids are disclosed having the general formula ##STR1## wherein R.sub.1 is hydrogen, lower alkyl, alkenyl, aryl or aralkyl; R.sub.2 is hydrogen, lower alkyl, aralkyl, alkanoyl or aroyl; R.sub.3 is lower alkyl, alkenyl or alkynyl; A is --CH.sub.2 --CH.dbd.CH-- or a single bond; X is oxygen, sulfur or NH; n is an integer from 1 to 8; and all stereoisomers thereof. These new compounds have been found to simultaneously inhibit the enzymes arachidonic acid cyclooxygenase and arachidonic acid 5-lipoxygenase and are therefore useful as antiinflammatory, antiasthma and antipsoriatic agents.

7-oxabicyclo(2.2.1)heptane-based derivatives useful as antiinflammatory,

Hydroximic acids of 7-oxabicycloheptane substituted ether and thioether prostaglandin analogs are provided having the structural formula ##STR1## wherein Y is O or ##STR2## and including all stereoisomers thereof. The compounds are inhibitors of prostaglandin and biosynthesis and as such are useful, for example, as anti-allergy and antiinflammatory agents and also as antipsoriatic agents.

Hydroximic acids of 7-oxabicycloheptane substituted ethers and

7-Oxabicyclo(2.2.1)heptane hydroxamic acid derivatives are disclosed having the general formula ##STR1## wherein R.sub.1 is hydrogen, lower alkyl, aryl, aralkyl or alkenyl; R.sub.2 is hydrogen, lower alkyl, alkanoyl or aroyl; R.sub.3 is lower alkyl, alkenyl or alkynyl; A is --CH.sub.2 --CH.dbd.CH-- or a single bond; and n is an integer from 0 to 9, with the proviso that when A is a single bond, n is an integer from 1 to 9; and including all stereoisomers and pharmaceutically acceptable salts thereof. These new compounds have been found to simultaneously inhibit the arachidonic acid enzymes cyclooxygenase and 5-lipoxygenase and are therefore useful as antiinflammatory, antiasthma and antipsoriatic agents.

7-Oxabicyclo(2.2.1)heptane hydroxamic acid derivatives useful as

7-Oxabicycloheptane substituted oxo prostaglandin analogs are provided having the structural formula ##STR1## wherein R.sup.1 is lower alkyl, aryl, aralkyl, cycloalkyl or cycloalkylalkyl, A is --CH.dbd.CH-- or --(CH.sub.2).sub.2 --, n is 1 to 4, m is 1 to 8, and R.sup.2 is ##STR2## wherein R.sup.4 is H or lower alkyl and including all steroisomers thereof. The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.

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Belle Mead, NJ, United States of America

Ravi K Varma