Miles Laboratories, Inc.

Brian T Warren

John W Spicer

Trevor S Abram

Peter Norman

Thomas Miller

Disclosed are trisubstituted benzene derivatives of the formula ##STR1## wherein B is selected from the group consisting of --NHCOC(CH.sub.3).sub.3, 1,3-oxazolinyl and --CONHR, wherein R is methyl, phenyl, or t-butyl; Y is selected from the group consisting of CO.sub.2 H, CHO, CO.sub.2 R' and COR', wherein R' is a lower alkyl having from 1 to 4 carbon atoms; and A is H or tetrahydropyran. Said compounds are valuable intermediates in the preparation of certain anti-allergic chromone or thiochromone-5-oxamic acid derivatives.

Trisubstituted benzene derivatives and a method for the preparation

1-(4-Cyano-phenoxy)-2-hydroxy-3-[2-(5-1H-tetrazolyl)-chromon-5-yloxy]-propa ne and its pharmacologically acceptable salts, are useful in the treatment of allergies, allergic asthma and inflammation.

1-(4-Cyano-phenoxy)-2-hydroxy-3-[2-(5-1H-tetrazolyl

Certain substituted cycloalkenochromones and pharmacologically acceptable salts thereof are disclosed as being useful in the treatment of allergies. The compounds have the structure: ##STR1## X is --O--, --S--, or --SO.sub.2. Y is from 1 to 4. R.sub.1 is H or alkyl, and R.sub.2 is H, alkyl, aryl, carboxyl, alkoxy, aralkoxy, or alkoxycarbonyl. When R.sub.1 is alkyl, R.sub.2 is hydrogen, alkyl or aryl. At least one of R.sub.2 and R.sub.3 is alkoxycarbonyl, carboxyl or tetrazolyl. R.sub.3 is carboxyl, alkylthio, alkylsulfonyl, alkylsulfinyl, alkoxycarbonyl, or tetrazolyl.

Cycloalkenochromone

Definitions: in the following Formulae I, II and IV, R.sup.1 represents hydrogen, alkyl of 1 to 4 carbon atoms, or a nontoxic cation, while each of R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 symbolizes hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, carboxy, carbalkoxy of 1 to 4 carbon atoms, trihalomethyl, halogen, nitro or cyano. Certain 1-(2-substituted-chromon-yloxy)-2-hydroxy-3-(substituted-phenoxy)propanes (Formula I), ##SPC1## can be synthesized from intermediate bis-(substituted-phenoxy)propanes (Formula II), ##SPC2## by condensation with diethyl oxalate in the presence of sodium ethoxide followed by cyclization with a mixture of glacial acetic acid and concentrated sulfuric or a mixture of concentrated hydrochloric acid and a lower alcohol containing up to 4 carbon atoms. The bis-(substituted-phenoxy)propane intermediates (Formula II) are prepared by reacting a dihydroxyacetophenone (Formula III), ##SPC3## with a (substituted-phenyl)glycidyl ether (Formula IV), ##SPC4## in an organic solvent in the presence of a catalyst. The 1-(2-substituted-chromon-yloxy)-2-hydroxy-3-(substituted-phenoxy)propanes (Formula I) are useful in the treatment of allergic conditions in mammals. The bis-(substituted-phenoxy)propanes (Formula II) are useful as intermediates in the synthesis of the latter compounds. Methods of preparing compounds having Formulae I and II are described. Methods of treating allergic conditions in mammals utilizing compounds of Formula I are also disclosed.

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Ickenham, United Kingdom

Brian T Warren