Lilly Industries, Inc.

Eli Lilly and Company

Eli Lilly Industries Limited

John P Verge

William J Ross

Martin Charles Neville

William B Jamieson

Winston S Marshall

William R Williamson

Robin G Simmonds

Henry Friedman

John Goldsworthy

David J Steggles

Alec Todd

Alex Todd

This invention provides novel alkane derivatives which are leukotriene antagonists, formulations of those derivatives, and a method of using those derivatives for the treatment of conditions characterized by an excessive release of leukotrienes.

Cyano and thiocyano intermediates

There are described compounds of the formula ##STR1## in which R.sup.1 is hydrogen or C.sub.1-6 alkyl, R.sup.2 is hydrogen, C.sub.1-6 alkyl or C.sub.3-6 alkenyl, X and Y are each oxygen, sulphur, sulphinyl or sulphonyl, n is 2 to 6 and Z is 1H-tetrazol-5-yl, 1H-tetrazol-5-ylthio, 1H-tetrazol-5-ylsulphinyl, 1H-tetrazol-5-ylsulphonyl, cyano or thiocyano, provided that when both X and Y are oxygen Z is 1H-tetrazol-5-ylthio, 1H-tetrazol-5-ylsulphinyl, 1H-tetrazol-5-ylsulphonyl or thiocyano; and salts thereof. The compounds in which Z is other than cyano or thiocyano have pharmaceutical activity and inhibit leukotriene action or formation.

Tetrazole substituted compounds and their anti-allergic use

There are described compounds of the formula ##STR1## in which R.sup.1 is hydrogen or C.sub.1-6 alkyl, R.sup.2 is hydrogen, C.sub.1-6 alkyl or C.sub.3-6 alkenyl, R.sup.3 is hydrogen or C.sub.1-6 alkyl, R.sup.4 is hydrogen or an N-protecting group, n is 2, 3, 4 or 5, and X is oxygen, sulphur or --CH.sub.2 --, provided that when X is --CH.sub.2 -- n is 0; and salts thereof. The compounds in which R.sup.4 is hydrogen have pharmaceutical activity.

N-[4-[.omega.-(4-acyl-3-hydroxyphenoxy)alkoxy]-p

Compounds of formula ##STR1## wherein R.sub.1, R.sub.2 and R.sub.3 are each independently selected from H, OH, C.sub.1 -C.sub.4 alkyl, R.sub.4 --CO and halogen, where R.sub.4 is C.sub.1 -C.sub.4 alkyl; R.sub.5 and R.sub.6 are each independently selected from H, C.sub.1 -C.sub.4 alkyl and optionally-substituted phenyl; R.sub.7 is an alkylene group having from 1 to 4 carbon atoms, optionally containing a substituted or unsubstituted phenyl group; p is 0 or 1; and Z is a 1H-tetrazol-5-yl or a --CN group; and salts thereof, may be prepared by reacting a compound of formula. ##STR2## with a compound of formula ##STR3## wherein R.sub.1 -R.sub.7 are as defined in claim 1, in an organic solvent at a temperature in the range of 40.degree.-120.degree. C. in the presence of a base, and reacting the resulting compound with an alkali metal cyanide or thiocyanate, and optionally reacting the resulting compound with a source of azide ions to produce pharmacologically active compounds of formula I wherein Z is 1H-tetrazol-5-yl.

Tetrazolyl compounds and their use as anti allergic agents

Leukotriene antagonists

There are described compounds of the formula ##STR1## in which R.sup.1 is hydrogen or C.sub.1-6 alkyl, R.sup.2 is hydrogen, C.sub.1-6 alkyl or C.sub.3-6 alkenyl, X and Y are each oxygen, sulphur, sulphinyl or sulphonyl, n is 2 to 6 and Z is 1H-tetrazol-5-yl, 1H-tetrazol-5-ylthio, 1H-tetrazol-5-ylsulphinyl, 1H-tetrazol-5-ylsulphonyl, cyano or thiocyano, provided that when both X and Y are oxygen Z is 1H-tetrazol-5-ylthio, 1H-tetrazol-5-ylsulphinyl, 1H-tetrazol-5-ylsulphonyl or thiocyano; and salts thereof. The compounds in which Z is other than cyano or thiocyano have pharmaceutical activity and inhibit leukotriene action or formation. '

Benzonitrile and benzothiocyano intermediates

Compounds of the following formula are described: ##STR1## in which n is 0, 1 or 2, R.sup.1 is C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, C.sub.1-4 alkylsulphonyl, trifluoromethyl, halo or nitro, and R.sup.2 and R.sup.3 are each independently hydrogen or C.sub.1-4 alkyl, and salts thereof. The compounds are useful in the treatment of immediate hypersensitivity conditions and are prepared by reaction of the appropriate formylquinolone with malonic acid, ylid or phosphonate.

Quinolone derivatives and their use in a method of controlling an

Novel hydantoin compounds are described of the formula (I): ##STR1## wherein Ar is phenyl optionally substituted by up to three radicals selected from the group comprising C.sub.1-6 alkoxy, halogen, 1,3-dioxol-2-yl, hydroxy C.sub.1-4 alkoxy C.sub.1-4 alkyl, phenyl, hydroxyl, nitrile, C.sub.1-4 haloalkyl, C.sub.1-4 alkyl, C.sub.2-4 alkenyloxy, C.sub.1-4 alkoxycarbonyl or phenoxy optionally substituted by C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy or halogen;

Thenyl hydantoins and anti-asthmatic compositions thereof

A class of novel 2-oxazolyl ureas and carbamates having anti-allergic activity are described together with methods of making such compounds and pharmaceutical compositions containing the active compounds of the invention.

Oxazole carbamates, formulations and asthma treatment

Treatment of immediate hypersensitivity diseases with aryl hydantoins

Pharmaceutical formulations are described, which comprise a hydantoin of formula (I): ##STR1## wherein R.sup.1 is C.sub.1-4 alkyl, R.sup.2 is hydrogen or C.sub.1-4 alkyl; or R.sup.1 and R.sup.2 taken together either represent a C.sub.4-6 alkylene group or a group of formula: ##STR2## where R.sup.5 and R.sup.6 independently represent hydrogen or C.sub.1-4 alkyl;

Method of treating asthma with alkyl, alkylidene and alkylene hydantoins

Hydantoin compounds are described of the formula (I) : ##STR1## wherein R.sup.1 is phenyl, C.sub.1-4 hydroxyalkyl or carboxy C.sub.1-4 alkyl and wherein R.sub.2 is C.sub.1-6 alkyl. The compounds are useful in the prophylactic treatment of immediate hypersensitivity diseases including asthma.

Treating immediate hypersensitivity conditions with 3,5-disubstituted

Oxazole ureas formulations and asthma treatment

Acylamino heteroaryl compounds in which the heteroaryl nucleus is a 1,2,4-oxadiazole or 1,2,4-thiadiazole nucelus, methods of making the compounds and pharmaceutical formulations containing the compounds. The compounds have anti-allergy activity.

Acylamino derivatives

Acylamino heteroaryl compounds in which the heteroaryl nucleus is a 1,2,4-oxadiazole or 1,2,4-thiadiazole nucleus, methods of making the compounds and pharmaceutical formulations containing the compounds. The compounds having anti-allergy activity.

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Henley-on-Thames, United Kingdom

John P Verge