American Cyanamid Company

Robert E Schaub

Martin J Weiss

Allan Wissner

Karel F Bernady

John F Poletto

Middleton Brawner Floyd

Seymour Bernstein

Janis Upeslacis

Middleton B Floyd, Jr

Kenneth E Green

Phaik E Sum

William J McGahren

Phaik-Eng Sum

Philip R Hamann

Thomas G Miner

The invention is a compound of R or S enantiomers or racemic mixtures of compounds of the formula: ##STR1## wherein: (A) X, Y, and R.sub.3 are as defined in the specification.

Certain hyrdoxy-phosphinyl-oxy-phenylmethyl-imidazolium hydroxide inner

The invention is novel compounds of the formula: ##STR1## which are antagonists of platelet activating factor.

Bis-arylphosphate ester antagonists of platelet activating factor

The invention is a compound of R or S enantiomers or racemic mixtures of compounds of the formula: ##STR1## wherein: (A) is ##STR2## Y is (i) C.sub.1 -C.sub.24

Certain phosphinyl-oxy-phenyl-methyl-pyridinium-hydroxide inner salts

The invention is a compound of R or S enantiomers or racemic mixtures of compounds of the formula: ##STR1## wherein: (A) X is

Certain hydroxy-phosphinyl-oxy-phenyl methyl-thiazolium hydroxide inner

Phospocholine derivatives having the formula: ##STR1## in which W, Z, Q and R are described in the specification are disclosed as useful for inhibiting the enzyme phospholipase A.sub.2. Methods of making and using the compounds are also disclosed.

Phosphocholine derivative inhibitors of phospholipase A.sub.2

The invention is novel compounds of the formula: ##STR1## wherein: X is a phenyl or naphthyl ring optionally substituted in any position with one to four substituents of;

Antihypertensive phosphate derivatives having the following formula are described: ##STR1## wherein X is selected from one or more of: (a) C.sub.1 -C.sub.24 branched or straight chain alkyl; (b) C.sub.1 -C.sub.24 branched or straight chain alkoxy; (c) ##STR2## wherein n and m are integers from 0 to 25 and the sum of n and m is less than or equal to 25; phenyl; substituted phenyl wherein the substituents are selected from the group consisting of C.sub.1 -C.sub.20 branched or straight chain alkyl, C.sub.1 -C.sub.20 branched or straight chain alkoxy, halogen, trifluoromethyl, phenyl, and substituted phenyl, phenoxy; and substituted phenoxy, wherein the substituents are selected from the group consisting of C.sub.1 -C.sub.20 branched or straight chain alkyl, halogen, trifluoromethyl, phenyl and substituted phenyl; Q is selected from the group consisting of: ##STR3## wherein R.sub.1 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.4 branched or straight chain alkyl, C.sub.1 -C.sub.4 branched or straight chain alkoxy and C.sub.1 -C.sub.4 branched or straight chain alkylamino and wherein R.sub.3 is C.sub.1 -C.sub.4 alkyl, with the proviso that when Q is ##STR4## then R.sub.1 is C.sub.1 -C.sub.4 branched or straight chain alkyl; T is a bivalent radical selected from the group consisting of --(CHR).sub.p -- and ##STR5## wherein p is an integer from 1 to 15, the moiety --(CHR).sub.p -- represents an alkylene chain substituted at any position with one or more C.sub.1 -C.sub.10 alkyl groups or phenyl groups, and the moiety ##STR6## is bound with the oxygen atom attached directly to the aromatic ring; and Z is ##STR7## wherein R.sub.2 is hydrogen or C.sub.1 -C.sub.4 branched or straight chain alkyl and q is an integer from 4 to 7; in either the racemic or optically active forms.

Antihypertensive phosphate derivatives and intermediates thereof

Antihypertensive phosphate derivatives are described having the following formula: ##STR1## wherein n is an integer 1 or 2; m is an integer 1 or 2, and the sum of n and m must be 3; X is selected from the group consisting of C.sub.1 -C.sub.24 branched or straight chain alkoxy and substituted phenoxy wherein the substituents are selected from one or more of the group consisting of C.sub.1 -C.sub.20 branched or straight chain alkyl, C.sub.1 -C.sub.20 branched or straight chain alkoxy, halogen, phenyl and substituted phenyl; T is selected from the group consisting of hydrogen and ##STR2## wherein R.sub.1 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.4 branched or straight chain alkyl, C.sub.1 -C.sub.4 branched or straight chain alkoxy and C.sub.1 -C.sub.4 branched or straight chain alkylamino, Q is a bivalent radical selected from the group consisting of --(CH.sub.2).sub.p -- and --(CHR).sub.p --, where p is an integer from 2 to 12 and the moiety --(CHR).sub.p -- represents an alkylene chain which is substituted by one or more C.sub.1 -C.sub.10 alkyl groups or phenyl groups; Z is selected from the group consisting of ##STR3## wherein R.sub.2 may be the same or different and is selected from the group consisting of hydrogen and C.sub.1 -C.sub.4 branched or straight chain alkyl and q is an integer from 4 to 7.

Antihypertensive phosphate derivatives

Antihypertensive phosphate derivatives having the following formula: ##STR1## wherein X is selected from one or more of C.sub.1 -C.sub.24 alkyl; C.sub.1 -C.sub.24 alkoxy; n and m are integers from 0 to 25 and the sum of which are less than or equal to 25; phenyl or substituted phenyl alkoxy, halogen, trifluoromethyl, phenyl, and substituted phenyl, phenoxy; and substituted phenoxy, wherein the substituents are C.sub.1 -C.sub.20 branched or straight chain alkyl, halogen, trifluoromethyl, phenyl and substituted phenyl; Q is selected from ##STR2## and --OR.sub.3 R.sub.1 is selected form hydrogen, C.sub.1 -C.sub.4 alkoxy and C.sub.1 -C.sub.4 alklyamino and R.sub.3 is C.sub.1 -C.sub.4 alkyl, with the provision that when Q is ##STR3## R.sub.1 is C.sub.1 -C.sub.4 branched or straight chain alkyl; T is a bivalent radical selected from alkylene or arylalkylene substituted at any position with one or more C.sub.1 -C.sub.10 alkyl with oxygen atom attached directly to the aromatic ring; Z is ##STR4## R.sub.2 is hydrogen or C.sub.1 -C.sub.4 branched straight chain alkyl; Q is an integer from 4-7.

Antihypertensive sulfonyl derivatives having the following formula are described: ##STR1## where R' is a C.sub.2 -C.sub.20 alkyl group,

Antihypertensive derivatives

Antihypertensive phosphate derivatives having the following formula are described: ##STR1## wherein X is a C.sub.1 -C.sub.24 branched or straight chain alkyl group; R is selected from the group consisting of hydrogen and C.sub.1 -C.sub.4 alkyl, with the proviso that at least one R group is not hydrogen; T is selected from the group consisting of hydrogen and ##STR2## wherein R.sub.1 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.4 branched or straight chain alkyl, C.sub.1 -C.sub.4 branched or straight chain alkoxy and C.sub.1 -C.sub.4 branched or straight chain alkylamino; Q is a bivalent radical selected from the group consisting of --(CH.sub.2).sub.p -- and --(CHR.sup.1).sub.p --, wherein p is an integer from 2 to 12 and the moiety --(CHR.sup.1).sub.p -- represents an alkylene chain which is substituted by one or more C.sub.1 -C.sub.10 alkyl groups or phenyl groups; Z is selected from the group consisting of ##STR3## wherein R.sub.2 may be chain alkyl and q is an integer from 4 to 7; in either the racemic or in the optically active form.

Antihypertensive phosphate derivatives having the following formula are described: ##STR1## wherein X is selected from one or more of: (a) C.sub.1 -C.sub.24 branched or straight chain alkyl; (b) C.sub.1 -C.sub.24 branched or straight chain alkoxy; (c) ##STR2## wherein n and m are integers from 0 to 25 and the sum of n and m is less than or equal to 25; phenyl; substituted phenyl wherein the substituents are selected from the group consisting of C.sub.1 -C.sub.20 branched or straight chain alkyl, C.sub.1 -C.sub.20 branched or straight chain alkoxy, halogen, trifluoromethyl, phenyl, and substituted phenyl, phenoxy; and substituted phenoxy, wherein the substituents are selected from the group consisting of C.sub.1 -C.sub.20 branched or straight chain alkyl, halogen, trifluoromethyl, phenyl and substituted phenyl; Q is selected from the group consisting of: ##STR3## wherein R.sub.1 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.4 branched or straight chain alkyl, C.sub.1 -C.sub.4 branched or straight chain alkoxy and C.sub.1 -C.sub.4 branched or straight chain alkylamino and wherein R.sub.3 is C.sub.1 -C.sub.4 alkyl, with the proviso that when Q is ##STR4## then R.sub.1 is C.sub.1 -C.sub.4 branched or straight chain alkyl; T is a bivalent radical selected from the group consisting of --(CHR).sub.p -- and ##STR5## wherein p is an integer from 1 to 15, the moiety --(CHR).sub.p -- represents an alkylene chain substituted at any position with one or more C.sub.1 -C.sub.10 alkyl groups or phenyl groups, and the moiety ##STR6## is bound with the oxygen atom attached directly to the aromatic ring; and Z is ##STR7## wherein R.sub.2 is hydrogen or C.sub.1 -C.sub.4 branched or straight chain alkyl and q is an interger from 4 to 7; in either the racemic or optically active forms.

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Upper Saddle River, NJ, United States of America

Robert E Schaub