LEUKOTRIENE ANTAGONISTS, THEIR PRODUCTION, AND COMPOSITIONS CONTAINING THEM

Abstract: Compounds of the formulae: and their pharmaceutically acceptable (including acid-­ addition) salts, which are novel, are antagonists of leukot­ rienes of C₄, D₄ and E₄, the slow reacting substance of anaphylaxis. They can be made into pharmaceutical com­ positions by incorporating them in a pharmaceutical carrier. In the formulae, each R is H, OH, SH C₁ ₆ alkyl C₂ ₆ alkenyl, CF₃, C₁ ₆ alkoxy, C₁ ₆ alkylthio, benzyl, phenethyl, halogen, amino, N(R₄)₂, COOR₄ or CH₂OR₄ where R₄ is H or C₁ ₆ alkyl, formyl, CN, CF₃S or NO₂; each R′ is R₄; OR₄; COOR₄; N(R₄)₂; SR₄; CH₂OR₄ or CHO; or together R′ and R′ are O, CH₂ or Y′ is sulfur, sulfoxide, sulfone, = NR₁₁, = NR₁₂, = N - CO - R₁₃, - N - CN, CH₂ or C = 0 where R₁₁ is H, C₁₋₄ alkyl, C₁ ₄ alkanoyl, phenylsulfonyl or p-toluenesulfonyl, R₁₂ is H or C₁₋₄ alkyl and R₁₃ is C₁₋₄ alkyl or C₁₋₄ alkoxy; Y is of the type defined for Y′ or oxygen; each R₁ is hydrogen C₁₋₃ alkyl; each m is 0 or an integer from 1 to 6; where each R₆ is H or C₁₋₄ alkyl; each R₇ is H, OH or C₁₋₄ alkyl; and each R₈ is H or C₁₋₄ alkyl and is absent when the two indicated carbons are triply bonded; R₅ is COOR₄; CH₂OH, CHO: tetrazole; NHSO₂R₁₄; CON­ HSO₂R₁₄; hydroxymethylketone; CN; CON(R₇)₂; a monocy­ clic or bicyclic heterocyclic ring containing an acidic hydroxyl group; or COOR₁₅ where R₁₅ is: where each s is independently 0-3, R₆ is as defined above and R₁₆ is (A) a monocyclic or bicyclic heterocyclic radical contain­ ing from 3 to 12 nuclear carbon atoms and 1 or 2 N heteroatoms or one N and one S heteratom, each ring in the heterocyclic radical being formed of 5 or 6 atoms, or (B) W-R₁₇ where W is O, S or NH and R₁₇ contains up to 21 carbon atoms and is (1) a hydrocarbon radical or (2) an acyl radical or an organic acyclic or monocyclic carboxylic acid containing not more than 1 heteroatom in the ring; each of r and q is 0-20 but r + q does not exceed 20; and p is 0 or 1; R₃ is C₁₋₆ alkyl or C₃₋₆ alkenyl; R₉ is C₁₋₆ alkyl, C₁ ₆ alkoxy or (CH₂) r R₅, where r and R₅ are as defined above; and R₁₀ is H, C₁₋₆ alkyl; R₄CO- or R₄OCH₂, where R₄ is as defined above and R₁₄ is OH, C₁₋₆ alkoxy, C₁₋₆ acyl, phenyl, phenyl having C₁₋₃ alkyl or C₁₋₃ alkoxy substitution, halogen, halogenated alkyl, carboxy, cyano or formyl.

Description: LEUXOTRI ENE ANTAGONISTS, ThEIR PRODUCTION, AND COMPOSITIONS CONTAINING ZEN Although the chemical identity of leukotrienes was not discovered until 1979, their history actually began in Australia in 1938 when researchers discovered slow reacting substances (SRS) which caused slow contractions of smooth muscle. When their chemical identity was learned, SRS was found to be a mixture of three previously unknown substances which are related chemically to the prostaglandins and thromboxanes. They were named leukotrienes because they are made by leukocytes and have three conjugated double bonds. Leukotrienes have major effects on the smaller peripheral airways of the lungs and on the larger central passages which include the trachea and the bronchi. In the presence of an allergy trigger, like pollen or dust, leukotrienes are manufactured from fatty substances trapped in the membrane of a triggered cell. A series pf reactions within the cell generates a set of different leukotrienes which are transported through the cell membrane into the blood. Then they bring about a constriction of the air passages leading to breathlessness. The present invention provides compounds of Formula XI and XII below, and compounds that are their pharmaceutically acceptable salts. Compounds of these formulae can act as antagonists to prevent leukotriene action or as inhibitors to prevent synthesis, and can prevent or reverse leukotriene action or prevent leukotriene synthesis when administered orally. The compounds can be administered by insufflation, intravenously, rectally, topically, parenterally, including subcutaneously and intramuscularly, or nasally, and the present invention also provides pharmaceutical compositions containing the said compounds and a pharmaceutical carrier. Such compositions may be suitable for administration in the ways stated. Because of their activity as leukotriene antagonists, compounds of the present invention are useful as anti-asthmatic, anti-allergic, and anti-inflammatory agents and are useful in treating allergic rhinitis and chronic bronchitis and for amelioration of skin diseases like psoriasis and atopic eczema. These compounds are also useful to antagonize or inhibit the properties of leukotrienes relating to cardiovascular and vascular systems. The compounds of the present invention have the Formulae: EMI3.1 wherein each R is independently H, OH, alkyl of 1 to 6 carbon atoms which may be straight chain or branched; alkenyl of 2 to 6 carbon atoms which may be straight chain or branched; trifluoromethyl; alkoxy of 1 to 6 carbon atoms which may be straight chain or branched; SH; thioalkyl of 1 to 6 carbon atoms which may be straight chain or branched; phenyl; phenyl substituted by alkyl of 1 to 3 carbon atoms or by halogen; benzyl; phenalkyl with 2 to 4 alkyl carbon atoms; halogen, amino; N(R4)2 wherein R4 is H or alkyl of 1 to 6 carbon atoms which may be straight chain or branched; COOR4; CH20R4; formyl; CN; trifluoromethylthio; or nitro; each R' is independently R4; OR4; COOR4; N(R4)2; SR4; CH2OR4; CHO; or together R' and R' are 0; CH2; or EMI4.1 Y' is sulfur, sulfoxide, sulfone; EMI4.2 wherein R11 is H, alkyl of 1-4 carbon atoms which may be straight chain or branched; alkanoyl of 1-4 carbon atoms which may be straight chain or branched; phenylsulfonyl; tosyl; NR12 wherein R12 is H, alkyl of 1-4 carbon atoms which may be straight chain or branched; or EMI4.3 wherein R13 is alkyl of 1-4 carbon atoms which may be straight chain or branched, alkoxy of 1-4 carbon atoms which may be straight chain or branched; or N-CN, CH2, C=O. Y is Y' and oxygen; each R1 is independently hydrogen or alkyl of 1-3 carbonatoms; each m is independently an integer from 0-6; and R2 is EMI5.1 each R6 is independently H or alkyl of 1-4 carbons; each R7 is in dependently H, OH, or alkyl of 1-4 carbons; each R8 is independently H, or alkyl of 1-4 carbons, and is absent when a triple bond is present; R5 is COOR4; CH2OH; CHO; tetrazole; NHSO2R14; hydroxymethylketone; CONHSO2'R14; CN; CON(R7)2; a monocyclic or bicyclic heterocyclic ring containing an acidic hydroxyl group; or COOR15 where R15 is: EMI5.2 wherein each s is independently 0-3; R16 is A) a monocyclic or bicyclic heterocyclic radical containing from 3 to 12 nuclear carbon atoms and 1 or 2 nuclear heteroatoms selected from N and S with at least one being N, and with each ring in the heterocyclic radical being formed of 5 or 6 atoms, or B) the radical W-R17 wherein W is 0, S or NH and R17 contains up to 21 carbon atoms and is (1) a hydrocarbon radical or (2) an acyl radical of an organic acyclic or monocyclic carboxylic acid containing not more than 1 - heteroatom in the ring; R14 is OH, alkyl or alkoxy of 1 to 6 carbon atoms, phenyl or phenyl substituted by alkyl or alkoxy groups of 1 to 3 carbon atoms, halogen, hydroxy, haloalkyl, COOH, CN, formyl acyl of 1 to 6 carbon atoms or perfluoroalkyl of 1 to 4 carbon atoms; r and q are each independently 0-20 provided that the total of r and q does not exceed 20; and p is O or 1; R3 is alkyl of 1 to 6 carbon atoms which may be straight chain or branched; or alkenyl of 3 to 6 carbon atoms which may be straight chain or branched as illustrated in Formulae IV and V; R9 is alkyl of 1 to 6 carbon atoms which may be straight chain or branched; OH, alkoxy of 1 to 6 carbon atoms which may be straight chain or branched; or (CH2)rR5; R10 is H; alkyl of 1 to 6 carbon atoms 0 which may be straight chain or branched; R4C or R4OCH2-; and a pharmaceutically acceptable salt or acid addition salt thereof. In addition to the substituent definitions described above, the compounds of Formulae XI and XII also include the following: EMI6.1 all other definitions remaining the same, except that when one of the R7 groups is hydroxy, Y' may be oxygen. As used herein, the terms "each independently" or the equivalents thereof are employed to describe a number of possible position isomers and/or structural variations. For example, as described above, R2 is: EMI7.1 The letters r and q, represent possible alkane chains of from 0-20 carbon atoms, each having the R6 and R7 substituent groups. On each carbon atom of the alkane chain, the R6 and/or R7 substituent may be different. The above description therefore contemplates structures such as the following for the segments -(CR6R7)r- and -(CRgR7) EMI7.2 EMI7.3 and the like. The compounds of the present invention may be prepared by several different routes. According to one method a compound of Formula I is reacted with an optionally alkyl substituted alkenyl halide of Formula II wherein X is halogen and each R6 is independently H or alkyl of 1-4 carbon atoms to yield the corresponding 2-hydroxy-4-alkenyloxy-acetophenone of Formula III. The compound of Formula III is then subjected to a Claisen rearrangement to yield a 2, 4-dihydroxy-3-alkenyl-acetophenone compound of Formula IV. This rearrangement occurs on heating the compound of Formula III either neat or in a high boiling solvent, such as a halogenated hydrocarbon, e.g., dichlorobenzene, at from about 160 to about 2100C. The double bond in the compound of Formula IV may then be reduced, e.g., by catalytic hydrogenation with a catalyst such as Pd/C, to yield the corresponding saturated compound of Formula V. EMI8.1 The compound of Formula V is then reacted with a dihaloalkane of Formula VIa or a dihaloalkene of Formula VIb wherein X, R and m have the meaning given previously, to yield a 4-(haloalkyloxy)-3alkyl-2-hydroxyacetophenone compound of Formula VII. The reaction takes place by refluxing a mixture of the compounds of Formulae V and VIa or VIb in an inert solvent such as, for example, methylethylketone (MEK), acetone, tetrahydrofuran (THF), triglyme or dichloromethane in the presence of a base. The reflux temperature is preferably in the range of from about 60 to about 1300C. The base may be an alkali metal carbonate, for example, Li2O03, Na2CO3 or K2CO3. Specific examples of dihaloalkane compounds of Formula VIa are 1,3-dibromopropane, 2-methyl-1,3- dibromopropane, 2,2-dimethyl-l, 3-dibromopropane, 3-chloro-2-chloromethyl-l-propene, 1,3-dibromobutane, 1, 4-dibromobutane, 1, 5-dibromopentane, 1,6-dibromohexane, 1,7-dibromoheptane, l,S-dibromooctane, 1,9-di- bromononane, 1,10-dibromodecane, and 1,12-dibromododecane. A specific example of a dihaloalkene compound of Formula VIb is 1,4-dibromo-2-butene. EMI9.1 EMI10.1 wherein Q La EMI10.2 EMI10.3 In lieu of the dihaloalkane or dihaloalkene, the compound of Formula IV or V may be reacted with an epihalohydrin, e.g., epichlorohydrin, under the same conditions to yield the 4-(2,3-epoxypropyloxy)3-alkyl or 3-alkenyl-2-hydroxy-acetophenone compound of Formula VIII. EMI10.4 An alternative procedure is to react a compound of Formula II with a compound of Formula V to yield a 4-alkenyloxy-3-alkyl-2-hydroxy-acetophenone compound of Formula IX which is then epoxidized with an organic peracid such as, for example, m-chloroperbenzoic acid to give the compound of Formula VII I. EMI11.1 The reaction of a compound of Formula VII with a compound of Formula X, under the same conditions used to react a compound of Formula V with a compound of Formula VIa or VIb, gives compounds of the Formulae XI or XII. The reaction of a compound of Formula VIII with a compound of Formula X under the same conditions used to react a compound of Formula V with a compound of Formula VIa or VIb gives a compound of Formula XI wherein each m is 1. EMI11.2 When Y' is -CH2-, HY' is methyl. When EMI12.1 HY' is a protected aldehyde, such as, for example, dithioacetal. When Y' is methylene or carbonyl a stronger base such as, for example, lithium diisopropylamide or butyl lithium is employed in an inert solvent such as tetrahydrofuran with a suitable compound of Formula X. A compound of Formula X is prepared by subjecting a compound of the Formula XIII EMI12.2 wherein P is H or a protecting group such as, for example, methyl, benzyl, i-nitrobenzyl or 3-(m-nitrophenyl)-l-phenyl-l-oxo-3-propyl to a Friedel-Crafts reaction with an acyl halide or an acid anhydride. Other compounds of Formula XI and XII are obtained by reacting a compound of Formula VII with a compound of Formula X under the same conditions used to react a compound of Formula V. with a compound of Formula VIa or VIb. Alternatively, the compounds of Formulae XI and XII may be prepared by reacting a compound of Formula X with a compound of Formula VIa or VIb or an epihalohydrin under the same conditions as described for the preparation of the compound of Formula VII to give a compound of the Formula XIVa, XIVb or XIVc respectively. The latter are then reacted under the same conditions with a compound of the Formula V to give compounds of the Formulae XI or XII. EMI13.1 Alternatively, but less preferably, the compounds of Formulae IV or V, X and either VIa, VIb or epihalohydrin may. be reacted simultaneously under the conditions described above for reacting a compound of Formula VIa or Vib or epihalohydrin with a compound of Formula X. Prodrug ester derivatives of the compounds of Formulae XI and XII may be prepared using conventional synthetic techniques available to the skilled artisan. For example, compounds of the Formula XVI: EMI14.1 may be prepared as follows: Method A: EMI14.2 In Method A the carboxylic acid of Formula XVÏI is reacted in the presence of a base with an alkylhalide compound to provide the prodrug ester. Method B: EMI15.1 In Method B the sulfone carboxylic acid of Formula XVII I is similarly reacted with an appropriate alkylhalide in the presence of base to provide the corresponding prodrug ester. Method C: EMI15.2 EMI16.1 In Method C, the product of the Method A reaction, a prodrug ester, may be selectively oxidized to yield the sulfone or the sulfoxide compound. In the above structures, when R7=OH and R5=COOH, a lactone ring may be formed which would act as a prodrug form of the hydroxy acid. For example, a dehydration reaction of a compound having the Formula XIX: EMI16.2 such as, by reaction with trifluoroacetic acid would vield a lactone comPound having the formula: EMI16.3 which when administered orally to a mammal would release the hydroxy acid form of the compound in vivo. The magnitude of a prophylactic or therapeutic dose of a compound of Formula XI or XII will, of course, vary with the nature of the severity of the condition to be treated and with the particular compound of Formula XI or XII and its route of administration. In general, the daily dose range lies within the range of from about 0.2 mg to about 100 mg per kg body weight of a mammal. The pharmaceutical compositions of the present invention comprise a compound of Formula XI or- XII as an active ingredient, and may also contain a pharmaceutically acceptable carrier and optionally other therapeutic ingredients. The compositions include compositions suitable for oral, rectal, ophthalmic, pulmonary, nasal, dermal, topical or parenteral (including subcutaneous, intramuscular and intravenous) administration, although the most suitable route in any given case will depend on the nature and severity of the conditions being treated and on the nature of the active ingredient. They may be conveniently presented in unit dosage form and prepared by any of the methods well-known in the art of pharmacy. For use where a composition for intravenous administration is employed, a suitable dosage range is from about 0.2 to about 20 mg (preferably from about 1 to about 10 mg) of a compound of Formula XI or XII per kg of body weight per day and in the case where an oral composition is employed a suitable dosage range is, e.g. from about 1 to about 100 mg of a compound of Formula XI or XII per kg of body weight per day, preferably from about 5 to about 40 mg/kg. For administration by inhalation, the compounds of the present invention are conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebuliser. The preferred composition for inhalation is a powder which may be formulated as a cartridge from which the powder composition may be inhaled with the aid of a suitable device. In the case of a pressurized aerosol, the dosage unit may be determined by providing a valve to deliver a metered amount. Pharmaceuticalcompositions of the present invention suitable for oral administration and by inhalation in the case of asthma therapy may be presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient, as a powder or granules, or as a solution or a suspension in an aqueous liquid, a non-aqueous liquid, an oil-in-water emulsion or a water-in-oil liquid emulsion. Such compositions may be prepared by any of the methods of pharmacy but all methods include the step of bringing into association the active ingredient with the carrier which constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and intimately admixing the active ingredient with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product into the desired presentation. For example, a tablet may be prepared by compression or moulding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine, the active ingredient in a free-flowing form such as powder or granules, optionally mixed with a binder, lubricant, inert diluent, lubricating, surface active or dispersing agent. Moulded tablets may be made by moulding in a suitable machine, a mixture of the powdered compound moistened with an inert liquid diluent. Desirably, each tablet contains from about 25 mg to about 500 mg of the active ingredient and each cachet or capsule contains from about 25 to about 500 mg of the active ingredient. In addition to the compounds of Formulae XI and XII the pharmaceutical compositions can also contain other active ingredients, such as non-steroidal anti-inflammatory agents e.g. indomethacin, ibuprofen, sulindac, fenbufen, and the like, peripheral analgesic agents such as zomepirac, diflunisal and the like or cyclooxygenase inhibitors. They may also contain inhibitors of the biosynthesis of the leukotrienes such as are disclosed in copending case 16876, USSN 459,924, filed January 21, 1983 which is herein incorporated by reference and others known in the art. These pharmaceutical compositions may also contain antihistaminic agents such as Benadryl, Dramamine, Histadyl, Phenergan and the like. These pharmaceutical compositions containing Formulae XI or XII compounds and a second active ingredient are another embodiment of the invention. The weight ratio of the Formula XI or XII compound: second active ingredient may be varied and may range from 10:1 to about 1:10. The following examples illustrate the present invention without, however, limiting the same thereto. All temperatures are expressed in degrees Ceisius. EXAMPLE 1 4- (3- (4-Acetyl-3-hydroxy-2-propylphenoxy)propylthio) 2, 3-dichlorobenzeneacetic acid Step A. Preparation of 2,3-dichloro-4-methoxy acetophenone To a suspension of All3, 80 gm, in CH2C12, 1000 mL, was added dropwise acetylchloride, 31.6 gm. The solution was cooled at -5 C and 2,3-dichloroanisole, 70.8 gm, dissolved in CH2Cl2, 50 mL, was then added. The.solution was allowed to warm to room temperature and was stirred for 4 hours. The reaction mixture was poured on ice afld stirred for 30 minutes. The organic layer was decanted and the aqueous layer was extracted with CH2C12. The combined fractions were washed with brine, dried (Na2S04) and concentrated to a small volume. The addition of hexane caused crystallization of a solid which was filtered to yield the title compound, mp 73-770C. Analysis, calculated: C, 49.34; H, 3.68; C1, 32.36. Obtained: C, 49.09; H, 3.61; C1, 32.34. Step B: Preparation of 2,3-dichloro-4-methoxybenzene acetic acid, methyl ester To a mixture of 2,3-dichloro-4-methoxyacetophenone, 58 gm, methanol, 450 mL, and 70% perchloric acid, 88 mL, cooled to OOC, there was added thallium trinitrate trihydrate, 117 gm. The reaction mixture was allowed to warm to room temperature and was stirred for 18 hours. The mixture was poured in water, 700 mL, and was extracted twice with CH2C12, 500 mL. The combined organic fractions were washed successively with water, 5% NaHCO3 and with water, dried (Na2SO4) and concentrated in vacuo to yield, after purification by chromatography on silica gel, the title compound, as an oil, readily characterized by its NMR spectrum: (ppm) (CDC13) 3.85 (3H, s), 3.73 (2H, s), 3.68 (3H, s). Step C: Preparation of 2,3-dichloro-4-hydroxy benzeneacetic acid, methyl ester. 2,3-Dichloro-4-methoxybenzeneacetic acid, methyl ester, 46 gm, was refluxed for 18 hours in concentrated HBr, 350 mL. The reaction mixture was poured in water, 1.4 L, and the solution was extracted with EtOAc, 2 x 500 mL. The organic layers were washed with water, dried (Na2S04) and concentrated to dryness. The residue was slurried in 20% EtOAc-hexane to yield 2,3-dichloro-4-hydroxybenzeneacetic acid, mp 189-1900C. The acid was stirred at room temperature in methanolic HC1, 100 mL, for 30 minutes. The volatiles were removed in vacuo and the residue was slurried in hexane, filtered and air-dried to yield the title compound, mp 105-1060C. Analysis calculated: C, 45.98; H, 3.43; C1, 30.16. Obtained: C, 46.10; H, 3.65; C1, 30.31. Step D: Preparation of 2,3-dichloro-4-dimethyl thiocarbamoyloxybenzeneacetic acid, methyl ester Sodium hydride, 99%, 1.3 gm, was added to a solution of 2,3-dichloro-4-hydroxybenzeneacetic acid, methyl ester, 11.4 gm, in DMF, 100 mL. The mixture was stirred until evolution of H2 gas subsided. Dimethylthiocarbamoyl chloride, 6.5 gm, was then added and the reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was poured in water, 200 mL, and was extracted with ether, 500 mL. The ether layer was washed with water, dried (Na2S04) and concentrated in vacuo to yield an oil that was purified by chromatography on silica gel to yield the title compound, mp 87-930C. Analysis,-calculated: C, 44.73; H, 4.06; N, 4.34; S, 9.95; C1, 22.00. Obtained: C, 44.44; H, 4.15; N, 4.05; S, 9.05; C1, 21.65. Step E: Preparation of 2,3-dichloro-4-dimethyl carbamoylthiobenzeneacetic acid, methyl ester 2, 3-Dichloro-4-dimethylthiocarbamoylbenzene- acetic acid, methyl ester, 10.7 gm, was heated under N2 atmosphere at 2500C for 30 minutes. The reaction mixture was cooled to room temperature and after a purification by chromatography on silica gel, the title compound, was obtained, mp 119-1220C. Analysis, calculated: C, 44.73; H, 4.06; N, 4.34; S, 9.95; C1, 22.00. Obtained: C, 44.50; H, 4.21; N, 4.25; S, 10.19; C1, 22.57. Step F: Preparation of the sodium salt of 2,3 dichloro-4-mercaptobenzeneacetic acid, methyl ester 2, 3-Dichloro-4-dimethylcarbamoylthiobenzene- acetic acid, methyl ester1.3.22 gm, was refluxed in methanol, 60 mL, containing sodium methoxide, 855 mg, for 1 hour. The reaction mixture, containing about 10 millimoles of the sodium salt of the title compound, in 60 mL MeOH, was used as such in Step G. Step G: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)propylthio) -2, 3-dichlorobenzene- acetic acid, methyl ester To 30 mL of the solution obtained in Step F was added 4- (3-bromopropoxy) -3-propyl-2-hydroxyaceto- phenone, 1.73 gm, and the reaction mixture was refluxed for 2 hours. It was then poured in water and extracted with EtOAc. The extract was washed with water, dried (Na2SU4-) and concentrated in vacuo. The title compound, mp 82-850C was obtained by chromatography of the residue on silica gel. Step H: Preparation of 4-(3-(4-acetyl-3-hydroxy 2-propylphenoxy)propylthio) -2, 3-dichloro- benzeneacetic acid The ester prepared in Step G, 964 mg, dissolved in 1N NaOH, 10 mL, and in methanol, 30 mL, was refluxed for 30 minutes. The volatiles were evaporated in vacuo. The residue was taken up in water and the resulting solution was acidified with 20% citric acid. The mixture was extracted with EtOAc, the extracts were washed with water, dried (Na2SO4) and concentrated in vacuo to yield the title compound, mp 119-122 C. EXAMPLE 2 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropylthio) -2, 3-dichlorobenzeneacetic acid Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylthio)-2,3 dichlorobenzeneacetic acid, methyl ester By following Step G of Example 1, but substituting 4- (2, 3-epoxypropoxy) -3-propyl-2-hydroxy- acetophenone for 4-(3-bromopropoxy)-3-propyl-2hydroxyacetophenone, the title compound,-mp 85-88 OC, was obtained. Step B: 4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2 hydroxypropylthio) -2, 3-dichlorobenzeneacetic acid By following Step H of Example 1, but substituting the product of Step A of this example for the ester of Step G of Example 1, the title compound, mp l51-1530C, was obtained. EXAMPLE 3 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)propylthio)2, 3-dichlorobenzeneacetic acid-S-oxide Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)propylthio)-2,3-dichlorobenzene- acetic acid-S-oxide, methyl ester The product obtained in Step G of Example 1, 1.4 gm, in CH2C12, 35 mL, was treated with m-chloroperbenzoic acid, 560 mg, for 15 minutes at 0 C. Ca(OH)2, 3 gm, was added and the resulting suspension was stirred for 10 minutes. The solids were filtered off and the filtrate was concentrated in vacuo to yield the title compound, mp 153-1550C. Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)propylthio) -2,3-dichlorobenzene- acetic acid-S-oxide By following Step H of Example 1, but substituting the product of Step A of this example for the ester of Step G of Example 1, the title compound, mp 162-1640C, was obtained. EXAMPLE 4 4(3- (4-Acetyl-3-hydroxy-2-propylphenoxy)propyl- sulfonyl)-2,3-dichlorobenzeneacetic acid Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)propylsulfonyl)-2,3-dichloro- benzeneacetic acid, methyl ester The product obtained in Step G of Example 1, 1.4 gm, in CH2C12, 35 mL, was treated with m-chloroperbenzoic acid, 1.15 gm, for 2 hours at room temperature. Ca(OH)2, 4 gm, was added and the resulting suspension was stirred for 10 minutes. The solids were filtered off and the filtrate was concentrated in vacuo to yield the title compound, mp 115-1180C, Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)propylsulfonyl) -2,3-dichloro- benzeneacetic acid By following Step H of Example 1, but substituting the product of Step A of this example for the ester of Step G of Example 1, the title compound, mp 180-1810C, was obtained. EXAMPLE 5 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy propylthio)-2,3-dichlorobenzeneacetic acid-S-oxide Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy 2-propyiphenoxy) -2-hydroxypropylthio) -2,3- dichlorobenzeneacetic acid-S-oxide, methyl ester By following Step A of Example 3, but substituting the product of Step A of Example 2 for the ester of Step G of Example 1, the title compound, mp 149-1520C, was obtained. Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylthio)-2,3- dichlorobenzeneacetic acid-S-oxide By following Step H of Example 1 but substituting the product of Step A of this example for the ester of Step G of Example 1, the title compound, mp l66-l700C, was obtained. EXAMPLE 64-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy propylsulfonyl) -2, 3-dichlorobenzeneacetic acid Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylsulfonyl)-2,3- dichlorobenzeneacetic-acid, methyl ester By following Step A of Example 4, but substituting the product of Step A of Example 2 for the ester from Step G of Example 1, the title compound, mp 122-1250C, was obtained. Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylsulfonyl)-2,3- dichlorobenzeneacetic acid By following Step H of Example 1, but substituting the product from Step A of this example for the ester of Step G of Example 1, the title compound, mp 181-1830C, was obtained. EXAMPLE 7 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)propylthio-2fluorobenzeneacetic acid Step A: Preparation of 4-methoxy-2-fluoroacetophenone By following Step A of Example 1, but substituting m-fluoroanisole for 2,3-dichloroanisole, the title compound, mp 50-520C, was obtained. Step B: Preparation of 4-methoxy-2-fluorobenzene acetic acid, methyl ester By following Step B of Example 1 but substituting 4-methoxy-2-fluoroacetophenone for 2,3-dichloro-4-methoxyacetophenone, the title compound, bp 112-1150C/1 Torr, was obtained. Step C: Preparation of 4-hydroxy-2-fluorobenzene acetic acid, methyl ester By following Step C of Example 1 but substituting 4-methoxy-2-fluorobenzeneacetic acid, methyl ester for 2,3-dichloro-4-methoxybenzeneacetic acid, methyl ester, 4-hydroxy-2-fluorobenzeneacetic acid was obtained as a sticky solid which was treated with methanolic HC1 to yield the title compound as an oil. It was characterized by its NMR spectrum: (ppm) (CDC13) 3.70 (3H, s, CH30), 3.55 (2H, s, CH2). Step D: Preparation of 2-fluoro-4-dimethylthio carbamoyloxybenzeneacetic acid, methyl ester By following Step D of Example 1 but substituting 4-hydroxy-2-fluorobenzeneacetic acid, methyl ester for 4-hydroxy-2, 3-dichlorobenzeneacetic acid, methyl ester, the title compound, mp 113-1140C, was obtained. Step B: Preparation of 2-fluoro-4-dimethyl carbamoylthiobenzeneacetic acid, methyl ester By following Step E of Example 1 but substituting 2-fluoro-4-dimethylthiocarbamoyloxy- benzeneacetic acid, methyl ester for 2,3-dichloro 4-dimethylthiocar bamoyloxybenzeneacetic acid, methyl ester, the title compound, mp 79-810C, was obtained. Step F: Preparation of the sodium salt of 2-fluoro-4-mercaptobenzeneacetic acid, methyl ester By following Step F of Example 1 but substituting 2-fluoro-4-dimethylcarbamoylthiobenzeneacetic acid, methyl ester for 2,3-dichloro-4-dimethylcarbamoylthiobenzeneacetic acid, methyl ester a solution of the title compound was obtained and was used as such in the following Step. Step G: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)propylthio-2-fluorobenzene acetic acid, methyl ester By following Step G of Example 1 but substituting the product of Step F of this example for the product of Step F of Example 1, the title compound, mp 63-650C, was obtained. Step H: Preparation of 4-(3-(4-acetyl-3-hydroxy 2-propylphenoxy) propylthio-2-fluorobenzene- acetic acid By following Step H of Example 1, but substituting the methyl ester of Step G of this example for the methyl ester of Step G of Example 1, the title compound, mp 154-1560C, was obtained. EXAMPLE 8 Sodium Salt of 4-(3-(4-Acetyl-3-hydroxy-2-propyl phenoxy) -2-hydroxypropylthio-2-fluorobenzeneacetic acid, monohydrate Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylthio-2-fluoro benzeneacetic acid, methyl ester By following Step G of Example 7, but substituting 4-(2,3-epoxypropoxy)-3-propyl-2-hydroxyacetophenone for 4-(3-bromopropoxy)-3-propyl-2- hydroxyacetophenone, the title compound was obtained as an oil. Analysis, calculated: C, 61.31; H, 6.04; F, 4.21; S, 7.11. Obtained: C, 61.08; H, 6.51; F, 3.93; S, 6.69. Step B: Preparation of the sodium salt of 4-(3-(4 acetyl-3-hydroxy-2-propylphenoxy) -2-hydroxy- propylthio-2-fluorobenzeneacetic acid, mono hydrate By following Step H of Example 7, but substituting the product of Step A of this example for the ester of Step G of Example 7, the corresponding acid of the title compound was obtained as an oil. It was treated with one equivalent of sodium hydroxide in water to yield, after evaporation of the water, the title compound, mp 75-830C. Analysis, calculated: C, 55.45; H, 5.50; F, 3.98; S, 6.73. Obtained: C, 55.55; H, 5.56; F, 4.71; S, 6.99. EXAMPLE 9 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropylthio)-2-fluorobenzeneacetic acid-S-oxide Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylthio)-2-fluoro- benzeneacetic acid-S-oxide, methyl ester By following Step A of Example 3, but substituting the title compound of Step A of Example 8 for the title compound of Step G of Example 1, the title compound is obtained. Step B: Preparation 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylthio)-2-fluoro- benzeneacetic acid-S-oxide By following Step H of Example 1, but substituting the product of Step A of this example for the ester of Step G of Example 1, the title compound is obtained. EXAMPLE 10 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropylsulfonyl)-2-fluorobenzeneacetic acid; and 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-1-propenylsulfonyl)-2-fluorobenzeneacetic acid Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylsulfonyl)- fluorobenzeneacetic acid, methyl ester By following Step A of Example 4, but substituting the product of Step A of Example 8 for the title compound of Step G of Example 1, the title compound, mp 118-1190C, was obtained. Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2- propylphenoxy)-2-hydroxypropylsulfonyl)- fluorobenzeneacetic acid; and 4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)-1 propenylsulfonyl)-2-fluorobenzeneacetic acid By following Step H of Example 1, but substituting the product of Step A of this example for the ester of Step G of Example 1, a mixture was obtained. After recrystallization from diethyl ether, 4- (3- (4-acetyl-3-hydroxy-2-propylphenoxy) -2- hydroxypropylsulfonyl) -2-fluorobenzeneacetic acid, mp 119-120 C, was obtained. The mother liquors were purified by chromatography on silica gel to yield 4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)-1-propenylsulfonyl)-2-fluoro-benzene acetic acid, mp 249-2510C. EXAMPLE 11 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)propylthio-3fluorobenzeneacetic acid Step A: Preparation of 4-dimethylthiocarbamoyloxy-3 fluorobenzeneacetic acid, methyl ester By following Step D of Example 7, but substituting 4-hydroxy-3-fluorobenzene acetic acid, methyl ester for 4-hydroxy-2-fluorobenzeneacetic acid, methyl ester, the title compound, was obtained as an oil which was characterized by its NMR spectrum: (ppm) (CDC13) 3.70 (3H, s, CH30), 3.60 (2H, S, CH2), 3.40 (3H, S, CH3N), 3.33 (3H, s, CH3N). Step B: Preparation of 4-dimethylcarbamoylthio-3 fluorobenzeneacetic acid, methyl ester By following Step E of Example 7, but substituting 4-dimethylthiocarbamoyloxy-3-fluoro- benzeneacetic acid, methyl ester for 4-dimethylthiocarbamoyloxy-2-fluorobenzeneacetic acid, methyl -ester, the title compound, was obtained as an oil which was characterized by its NMR spectrum: (ppm) (CDC13) 3.70 (3H, s, CH3), 3.63 (2H, s, CH2), 3.07 (6H, s, (CH3)2N). Step C: Preparation of the sodium salt of 3-fluoro-4 mercaptobenzeneacetic acid, methyl ester -By following Step F of Example 7, but substituting 4-dimethylcarbamoylthio-3-fluorobenzeneacetic acid, methyl ester for 4-dimethylcarbamoyl-2 fluorobenzeneacetic acid, methyl ester, a solution of the title compound was obtained and was used as such in the following Step. Step D: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylthio)-3-fluorobenzene- acetic acid, methyl ester By following Step G of Example 7, but substituting the product of Step C of this example for the product of Step F of Example 1, the title compound was obtained as an oil which was characterized by its NMR spectrum: (ppm) (CDCl3) 12.70 (lH, s, phenolic OH), 7.53 (1H, d, J=9Hz, H ortho to acetyl), 6.33 (lH, d, J=9Hz H meta to acetyl), 4.13 (2H, t, J=7Hz, CH2O), 3.67 (3H, s, CH30), 3.57 (2H, s, CH2), 2.53 (3H, s, CH3CO). Step E: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy) -propylthio) -3-fluorobenzene- acetic acid By following Step H of Example 7, but substituting the methyl ester of Step D of this example for the product of Step G of Example 7, the title compound, mp 84-850C, was obtained. EXAMPLE 12 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropylthio)-3-fluorobenzeneacetic acid Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy 2-propylphenoxy)-2-hydroxypropylthio)-3- fluorobenzeneacetic acid, methyl ester By following Step D pf Example 11, but substituting 4-(2,3-epoxypropoxy)-3-propyl-2hydroxyacetophenone for 4-(3-bromopropoxy)-3-propyl2-hydroxyacetophenone, the title compound was obtained as an oil which was characterized by its NMR spectrum: (ppm) (CDC13) 12.70 (1H, s), 7.53 (1H, d, J=9Hz), 6.33 (1H, d, J=9Hz), 3.67 (3H, s), 3.57 (2H, s), 2.53 (3H, s). Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylthio-3-fluoro- benzeneacetic acid By following Step H of Example 1, but substituting the title compound of Step A of this example for 4- (3- (4-acetyl-3-hydroxy-2-propylphenoxy) - propylthio-2,3-dichlorobenzeneacetic acid, methyl ester, the title compound, mp 113-114 C, was obtained. EXAMPLE 13 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propylthio-3chlorobenzeneacetic acid Step A: Preparation of 4-dimethylthiocarbamoyloxy-3 chlorobenzeneacetic acid, methyl ester By following Step D of Example 7, but substituting 4-hydroxy-3-chlorobenzeneacetic acid, methyl ester for 4-hydroxy-2-fluorobenzene acetic acid, methyl ester, the title compound, mp 76-780C was obtained. Step B: Preparation of 4-dimethylcarbamoylthio-3 chlorobenzeneacetic acid, methyl ester By following Step E of Example 7, but substituting 4-dimethylthiocarbamoyloxy-3-chlorobenzeneacetic acid, methyl ester for 4-dimethylthiocarbamoyloxy-2-fluorobenzeneacetic acid, methyl ester, the title compound, was obtained as an oil which was characterized by its NMR spectrum: (ppm) (CDC13) 3.60 (3H, s), 3.50 (2H, s) r 2.90 (6H, s). Step C: Preparation of the sodium salt of 3-chloro 4-mercaptobenzeneacetic acid, methyl ester By following Step F of Example 7, but substituting 4-dimethylcarbamoylthio-3-chlorobenzeneacetic acid, methyl ester for 4-dimethylcarbamoylthio2-fluorobenzeneacetic acid, methyl ester, a solution of the title compound was obtained and was used as such in the following Step. Step D: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylthio)-3-chlorobenzene- acetic acid, methyl ester By following Step G of Example 7, but substituting the product of Step C of this example for the product of Step F of Example 1, the title compound, mp 66-68 C, was obtained. Step E: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylthio)-3-chlorobenzene acetic acid By following Step H of Example 7, but substituting the methyl ester of Step D of this example for the product of Step G of Example 7, the title compound, mp 79-810C, was obtained. EXAMPLE 14 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propylthio)- 3-chlorobenzeneacetic acid-S-oxide Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylthio)-3-chlorobenzene acetic acid-S-oxide, methyl ester By following Step A of Example 3, but sXlbsti ting the title compound of Step D of Example 13 for the title compound of Step G of Example 1, the title compound, mp 90-910C, was obtained. Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylthio)-3-chlorobenzene acetic acid-S-oxide By following Step H of Example 1, but substituting the product of Step A of this example for the ester of Step G of Example 1, the title compound, mp 130-1320C, was obtained. EXAMPLE 15 4-(3-(4-Acety1-3-hydroxy-2-propylphenoxy)-propyl- sulfonyl)-3-chlorobenzeneacetic acid Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylsulfonyl)-3-chloro- benzeneacetic acid, methyl ester By following Step A of Example 4, but substituting the product of Step D of Example 13 for the title compound of Step G of Example 1, the title compound, mp 98-1000C, was obtained. Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylsulfonyl)-3-chloro- benzeneacetic acid By following Step H of Example 1, but substituting the product of Step A of this example for the ester of Step G of Example 1, the title compound, mp 132-1340C, was obtained. EXAMPLE 16 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropylthio)-3-chlorobenzeneacetic acid Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylthio)-3-chloro- benzeneacetic acid, methyl ester By following Step D of Example 13, but substituting 4-(2,3-epoxypropoxy)-3-propyl-2-hydroxyacetophenone for 4-(3-bromopropoxy)-3-propyl-2hydroxyacetophenone, the title compound, mp 55-580C, was obtained. Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxyprdpylthio)-3-chloro- benzeneacetic acid By following Step H of Example 1, but substituting the title compound of Step A of this example for 4- (3-(4-acetyl-3-hydroxy-2-propylphenoxy) - propylthio-2,3-dichlorobenzeneacetic acid, methyl ester, the title compound, mp 128-1290C, was obtained. EXAMPLE 17 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropylthio)-3-chlorobenzeneacetic acid-S-oxide Step A: Preparation 4- (3- (4-acetyl-3-hydroxy-2- propylphenoxy)-2-hydroxypropylthio)-3-chloro- benzeneacetic acid-S-oxide, methyl ester By following Step A of Example 3, but substituting the title compound of Step A of Example 16- for the title compound of Step G of Example 1, the title compound, mp 103-1040C, was obtained. Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylthio)-3-chloro- benzeneacetic acid-S-oxide By following Step H of Example 1, but substituting the product of Step A of this example for the ester of Step G of Example 1, the title compound, mp 119-1230C, was obtained. EXAMPLE 18 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy proPylsulfonyl)-3-chlorobenzeneacetic acid Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylsulfonyl)-3- chlorobenzeneacetic acid, methyl ester By following Step A of Example 4, but substituting the title compound of Step A of Example 16 for the title compound of Step G of Example 1, the title compound, mp 96-980C, was obtained. Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylsulfonyl)- chlorobenzeneacetic acid By following Step H of Example 1, but substituting the product of Step A of this example for the ester of Step G of Example 1, the title compound, mp 110-112bC, was obtained. EXAMPLE 19 4- (3--(4-Acetyl-3-hydroxy-2-propylphenoxy) -propylthio) benzeneacetic acid Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylthio)benzeneacetic acid methyl ester By following Step G of Example 1, but substituting 4-mercaptobenzeneacetic acid, methyl ester for 2,3-dichloro-4-mercaptobenzeneacetic acid, methyl ester, the title compound, was obtained as an oil which was characterized by its NMR spectrum: (ppm) (CDC13) 12.67 (1H, s), 7.63 (1H, d, J=9Hz), 6.40 (lH, d, J=9Hz), 4.13 (2H, t, J=6Hz), 3.70 (3Ht s), 3.60 (2H, s), 2.57 (3H, s). Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylthio)benzeneacetic acid By following Step H of Example 1, but substituting the product of Step A of this example for the title compound of Step G of Example 1, the title compound, mp 94"C, was obtained. EXAMPLE 20 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propylsulfonyl)-benzeneacetic acid Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylsulfonyl)-benzeneacetic acid, methyl ester By following Step A of Example 4, but substituting the title compound of Step A of Example 19 for the title compound of Step G of Example 1, the title compound, was obtained as an oil which was characterized by its NMR spectrum: (ppm) (CDC13) 12.67 (1H, s), 7.63 (1H, d, J=9Hz), 6.40 (1H, d, J=9Hz) , 4.13 (2H, t, J=6Hz) , 3.70 (3H, s) , 3.60 (2H, S), 2.57 (3H, s). Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylsulfonyl)-benzeneacetic acid By following Step H of Example 1, but substituting the title compound of Step A of this example for the title compound of Step G of Example 1, the title compound, mp 132-134 C, was obtained. EXAMPLE 21 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-methyl proylthio)-benzeneacetic acid Step A: Preparation of 4- (3-bromo-2-methylpropoxy) - 2-hydroxy-3-propylacetoPhenone To a solution of 2,4-dihydroxy-3-propylacetophenone, 10 gm, in methylethyl ketone, 250 mL, was added successively 2-methyl-l, 3-dibromopropane, 33.4 gm, and potassium carbonate, 11 gm. The suspension was stirred at reflux for 4 hours. The solids were filtered off, and were washed thoroughly with acetone. The filtrate was evaporated to dryness to yield the title compound as an oil after purification by chromatography on silica gel. -NMR (ppm) (CDC13) 3.95 (2H, d, J=7Hz), 3.55 (2H, d, J=7Hz), 1.20 (3H, d, J=7Hz). Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy) -2-methylpropylthio) -benzene- acetic acid, methyl ester By following Step A of Example 19, but substituting the title compound of Step A of this example for 4-(3-bromopropoxy)-3-propyl-2-hydroxyacetophenone, the title compound was obtained as an oil. NMR (ppm) (CDC13) 12.65 (1H, s), 7.58 (1H, a, J=9Hz), 6.40 (1H, a, J=9Hz), 3.60 (3H, s), 3.50 (2H, s), 2.55 (3H, s). Step C: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-methylpropylthio)-benzene acetic acid By following Step H of Example 1, but substituting the title compound of Step B of this example for the title compound of Step G of Example 1, the title compound, mp 96-980C, was obtained. EXAMPLE 22 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropylthio)-benzeneacetic acid Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylthio)-benzene acetic acid methyl ester By following Step A of Example 2, but substituting 4-mercaptobenzeneacetic acid, methyl ester for the title compound of Step F of Example 1, the title compound, was obtained as an oil. NMR (ppm) (CDC13) 12.77 (1H, s), 7.67 (1H, d, J=9Hz), 7.27 (2H, d, J=9Hz), 6.93 (2H, d, J=9Hz), 6.50 (1H, d, J=9Hz), 3.67 (3H, s). Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylthio)-benzene- acetic acid By following Step H of Example 1, but substituting the title compound of Step A of this example for the title compound of Step G of Example 1, the tiel-e compound, mp 105.40C, was obtained. EXAMPLE 23 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy propylthio)-3-fluorobenzoic acid Step A: Preparation of 4-dimethylthiocarbamoyloxy-3 fluorobenzoic acid, methyl ester By following Step D of Example 7, but substituting 4-hydroxy-3-fluoro-benzoic acid, methyl ester for 4-hydroxy-2-fluorobenzeneacetic acid, methyl ester, the title compound, mp 103-1040C, was obtained. Step B: Preparation of 4-dimethylcarbamoylt-hio-3- fluorobenzoic acid, methyl ester By following Step E of Example 7, but substituting 4-dimethylthiocarbamoyloxy-3-fluorobenzoic acid, methyl ester for 4-dimethylthiocarbamoyloxy-2-fluorobenzeneacetic acid, methyl ester, the title compound, mp 72-74 C, was obtained. Step C: Preparation of the sodium salt 4-mercapto 3-fluorobenzoic acid, methyl ester By following Step F of Example 7, but substituting 4-dimethylcarbamoylthio-3-fluorobenzoic acid, methyl ester for 4-dimethylcarbamoylthio-2fluorobenzeneacetic acid, methyl ester, a solution of the title compound was obtained and was used as such in the following step. Step D: Preparation of 4-(3-(4-acetyl-3-hydroxy 2-propylphenoxy)-2-hydroxypropylthio) 3-fluorobenzoic acid, methyl ester By following Step A of Example 12, but substituting 4-mercapto-3-fluorobenzoic acid, methyl ester for 4-mercapto-3-fluorobenzeneacetic acid, methyl ester, the title compound, mp 123-125 C, was obtained. Step E: Preparation of 4-(3-(4-acetyl-3-hydroxy 2-propylphenoxy)-2-hydroxypropylthio) 3-fluorobenzoic acid By following Step H of Example 1, but substituting the title compound of Step D of tbis example for the title compound of Step G of Example 1, the title compound, mp 171-1750C, was obtained. EXAMPLE 24 4-(3-(4-Acety1-3-hydroxy-2-propylphenoxy)-2-hydroxy- propylthio)-3-fluorobenzoic acid-S-oxide Step A: Preparation of 4- (3- (4-acetyl-3-hydroxy-2- propylphenoxy)-2-hydroxypropylthio)-3-fluoro- benzoic acid-S-oxide, methyl ester By following Step A of Example 3 but substituting the title compound of Step D of Example 23 for the title compound of Step G of Example 1, the title compound, mp 103-1040C, was obtained. Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy) -2-hydroxypropylthio) -3- fluorobenzoic acid-S-oxide By following Step H of Example 1, but substituting the title compound of Step A of this example for the title compound of Step G of Example 1, the title compound, mp 72-740C, was obtained. EXAMPLE 25 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropylsulfonyl)-3-fluorobenzoic acid Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylsulfonyl)- fluorobenzoic acid, methyl ester By following the indications of Step A of Example 4, but substituting the title compound of Step D of Example 23 for the title compound of Step G of Example 1, the title compound was obtained as an oil. NMR (ppm) (CDC13) 12.75 (1H, s), 7.85 (1H, d, J=9Hz), 6.35 (lH, d, J=9Hz), 3.95 (3H, s), 2.54 (3H, s). Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2-hydroxypropylsulfonyl)- fluorobenzoic acid By following Step H of Example 1, but substituting the title compound of Step A of this example for the title compound of Step G of Example 1, the title compound, mp 128-1290C, was obtained. EXAMPLE 26 4-(3- (4-Acetyl-3-hydroxy-2-propylphenoxy) -propylthio- 3-fluorobenzoic acid Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylthio)-3-fluorobenzoic acid, methyl ester By following Step D of Example 23, but substituting 4-(3-bromopropoxy)-3-propyl-2-hydroxyacetophenone for 4-(2,3-epoxypropoxy)-3-popyl-2- hydroxyacetophenone, the title compound, mp 62-650C, was obtained. Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylthio)-3-fluorobenzoic acid By following Step H of Example 1, but substituting the title compound of Step A of this example for the title compound of Step G of Example 1, the title compound, mp 128-1290C, was obtained. EXAMPLE 27 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propylthio)-3-fluorobenzoic acid-S-oxide Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylthio)-3-fluorobenzoic acid-S-oxide, methyl ester By following Step A of Example 3, but substituting the title compound of Step A of Example 26 for the title compound of Step G of Example 1, the title compound, mp 108-1090C, was obtained. Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylthio)-3-fluorobenzoic acid-S-oxide By following Step H of Example 1, but substituting the title compound of Step A of this example for the title compound of Step G of Example 1, the title compound, mp 175-1760C, was obtained. EXAMPLE 28 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propyl sulfonyl)-3-fluorobenzoic acid Step A: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylsulfonyl)-3-fluoro benzoic acid, methyl ester By following Step A of Example 4, but substituting the title compound of Step A of Example 26 for the title compound of Step G of Example 1, the title compound, mp 102-1030C, was obtained. Step B: Preparation of 4-(3-(-acetyl-3-hydroxy-2- propylphenoxy)-propylsulfonyl)-3-fluoro- benzoic acid By following Step H of Example 1, but substituting the title compound of Step A of this example for the title compound of Step G of Example 1, the title compound, mp 181-1820C, was obtained. EXAMPLE 29 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propylcyanamido)-benzeneacetic acid Step A: Preparation of 4-cyanamidobenzeneacetic acid, methyl ester To a mixture of p-aminobenzeneacetic acid, methyl ester, 1.65 gm, in sodium acetate, 1.4 gm, in H20, 15 mL, cooled at OOC, was added CNBr, 1.3 gm. The suspension was allowed to warm to room temperature and was stirred overnight. The title compound was then filtered off and had mp 77-790C after crystallization from EtOAc/hexane. Step B: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylcyanamido)-benzeneacetic acid, methyl ester By following Step G of Example 1, but substituting 4-cyanamidobenzeneacetic acid, methyl ester for 4-mercapto-2,3-dichlorobenzeneacetic acid, methyl ester, the title compound, mp 92-930C, was obtained. Step C: Preparation of 4-(3-(4-acetyl-3-hydroxy-2 propylphenoxy)-propylcyanamido)-benzeneacetic acid By following Step H of Example 1, but substituting the title compound of Step B of this example for the title compound of Step G of Example 1, the title compound, mp 130-1310C, was obtained. EXAMPLE 30 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propylthio) delta-hydroxybenzenebutanol Step A: Preparation of I: 4-(3-bromopropylthio) delta-oxo-benzenebutanol and II: 4(3-bromo propylthio) -delta-hydroxybenzenebutanol 4-(3-Bromopropylthio)-gamma-oxobenzenebutanoic acid (3.4 g, 10.3 mmoles) was dissolved in THF (25 ml) and cooled to -150. Borane-THF complex (10 ml, 10.4 mmoles)'was added dropwise over one hour. The solution warmed to room temperature with stirring over twelve hours. The reaction mixture was diluted with methanol and stirred for thirty minutes. The solution was evaporated to dryness, dissolved in toluene, cooled to 0 and treated with an excess of diazomethane. After twelve hours the reaction was evaporated to dryness and purified by HPLC to yield the title compounds: I mass spectrum M+ 298 II mass spectrum M+ 300 Step B: Preparation of 4-(3-(4-Acetyl-3-hydroxy 2-propylphenoxy) -propylthio)delta-hydroxy- - benzenebutanol The compound II from Step A above, (2.0 g, - 6.25 mmoles), 2,4-dihydroxy-3-propylacetophenone (1.94 g, 10 mmoles) and potassium carbonate (2.76 g, 20 mmoles) were heated at reflux in methyl ethyl ketone (20 ml) for six hours. The reaction mixture was cooled to room temperature, filtered and evaporated to dryness. HPLC afforded the title compound. Analysis, calculated: C, 66.64; H, 7.46; S, 7.41. Obtained: C, 66.65; H, 7.40; S, 7.30. EXAMPLE 31 4(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propylsulfonyl)-delta-hydroxybenzenebutanol The compound of Example 30, Step B, (1.0 g, 2.32 mmole) was dissolved in chloroform and cooled to 00. A solution of m-chloroperbenzoic acid (1.0 g, 4.8 meq.) in chloroform was added dropwise. The reaction stirred at 0 for one hour. Calcium hydroxide (590 mg) was added and the reaction stirred twenty-five minutes. The mixture was filtered and evaporated to dryness. Crystallization of the residue from ethyl acetate-hexane afforded the title compound, m.p. 74-750, Analysis, calculated: C, 62.05; H, 6.94; S, 6.90. Obtained: C, 62.07; H, 6.92; S, 6.72. Similarly there may be prepared the following compounds: EXAMPLE 32 D,L-4- (3- (4-acetyl-3-hydroxy-2-propylphenoxy) propyl thio) -alpha-hydroxybenzeneacetic -acid Analysis, calculated: C, 63.29; H, 6.04; S, 7.68. Observed: C, 63.26; H, 6.13; S, 7.50. EXAMPLE 33 D,L-4- (3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl- sulfonsl)-alPha-hydroxybenzeneace-tic acid Analysis, calculated: C, 58.66; H, 5.82; S, 7.12. Observed: C, 58.75; H, 5.85; S, 6.97. m.p. 160-1610C. EXAMPLE 34 D,L-4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl oxy)-alpha-hydroxybenzeneacetic acid Analysis, calculated: C, 65.66; H, 6.51. Observed: C, 65.79; H, 6.56. EXAMPLE 35 D,L-4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl- thio)-3-bromo-alpha-hydroxybenzeneacetic acid EXAMPLE 36 D,L-4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylthio)-3-fluoro-alpha-hydroxybenzeneacetic acid EXAMPLE 37 D,L-2- (4- (3- (4-acetyl-3-bydroxy-2-propylphenoxy)propyl- oxy)-alpha-hydroxybenzeneacetic acid EXAMPLE 38 Methyl 4-(4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)- propylthio)phenyl) -3-methyl-3 (E) -butenoate EXAMPLE 39 4-(4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylthio)phenyl)-3-methyl-3(E)-butenoic acid EXAMPLE 40 Methyl 4-(4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)- propylthio)phenyl)-3-methyl-3(Z)-butenoate EXAMPLE 41 4-(4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylthio)phenyl)-3-methyl-3(Z)-butenoid acid It is understood that for those compounds which contain asymmetric centers, the present invention includes the racemic mixture as well as the individual resolved optical isomers.

Claims: WHAT IS CLAIMED IS: 1. A compound having either of the following Formulae EMI51.1 wherein each R is independently H, OH, alkyl of 1 to 6 carbon atoms which may be straight chain.or branched; alkenyl of 2 to 6 carbon atoms which may be straight chain or branched; trifluorometbyl; alkoxy of 1 to 6 carbon atoms which may be straight.chain or branched; SH; thioalkyl of 1 to 6 carbon atoms which may be straight chain or branched; phenyl; phenyl substituted by alkyl of 1 to 3 carbon atoms or by halogen; benzyl; phenethyl; halogen, amino; N(R4)2 wherein R4 is'H or alkyl of 1 to 6 carbon atoms which may be straight chain or branched; COOR4; CH2OR4; formyl; CN; trifluoromethylthio; or nitro; each R' is independently R4; OR4; COOR4; N(R4)2; SR4; CH2OR4; CHO; or together R' and R' are O; CH2; EMI52.1 Y' is sulfur, sulfoxide, sulfone; EMI52.2 wherein R11 is H, alkyl of 1-4 carbon atoms which may be straight chain or branched; alkanoyl of 1-4 carbon atoms which may be straight chain or branched; phenylsulfonyl; tosyl; NR12 wherein R12 is-H, $alkyl of 1-4 carbon atoms which may be straight chain or branched; or EMI52.3 wherein R13 is alkyl of 1-4 carbon atoms which may be straight chain or branched, alkoxy of 1-4 carbon atoms which may be straight chain or branched; or N-CN, CH2, C=O. Y is Y' and oxygen; each R1 is independently hydrogen or alkyl of 1-3 carbon atoms; each m is independently an integer from 0-6; and EMI52.4 each R6 is independently H or alkyl of 1-4 carbons; each R7 is independently H, OH, or alkyl of 1-4 carbons; each R8 is independently H, or alkyl of 1-4 carbons, and is absent when a triple bond is- present; R5 is COOR4; CH2OH; CHO; tetrazole; NHSO2R14; hydroxymethylketone; CONHSO2R14; CN; CON(R7)2; a monocyclic or bicyclic heterocyclic ring containing an acidic hydroxyl group; or COOR15 where R15 is: EMI53.1 wherein each s is independently 0-3; R16 is A) a monocyclic or bicyclic heterocyclic radical containing from 3 to 12 nuclear carbon atoms and 1 or 2 nuclear heteroatoms selected from N and S with at least one being N, and with each ring in the heterocyclic -radical being formed of 5 or 6 atoms, or B) the radical W-R17 wherein W is O, S or NH and R17 contains up to 21 carbon atoms and is (1) a hydrocarbon radical or (2) an acyl radical of an organic acyclic or monocyclic carboxylic acid containing not more than 1 heteroatom in the ring; r an q are each independently 0-20 provided that the total of r and q does not exceed 20; and p is 0 or 1; R3 is alkyl of 1 to 6 carbon atoms which may be straight chain or branched; or alkenyl of 3 to 6 carbon atoms which may be straight chain or branched as illustrated in Formulae IV and V; Rg is alkyl of 1 to 6 carbon atoms which may be straight chain or branched; alkoxy of 1 to 6 carbon atoms which may be straight chain or branched; or (CH2)rR5; Rln is H; alkyl of 1 to 6 carbon atoms which may be straight chain or branched; EMI54.1 or R4OCH2-; R14 is OH, alkyl or alkoxy of 1 to 6 carbon atoms, phenyl or phenyl substituted by alkyl or alkoxy groups of 1 to 3 carbon atoms, halogen, hydroxy, haloalkyl, COOH, CN, formyl acyl of 1 to 6 carbon atoms or perfluoroalkyl of 1 to 4 carbon atoms; and a pharmaceutically acceptable salt or acid addition salt thereof. 2. A compound of Claim 1 wherein Y is oxygen and Y! is sulfur, sulfoxide, sulfone, amino or cyanamido. 3. A compound of Claim 1 wherein Y' is oxygen and Y is oxygen, sulfur, sulfoxide, sulfone, amino or cyanamido and R2 is EMI54.2 wherein at least one R7 is OH. 4. A compound of Claim 1 having the name: 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)propyl thio)-2,3-dichlorobenzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2 hydroxypropylthio) -2, 3-dichlorobenzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)propyl thio) -2, 3-dichlorobenzeneacetic acid-S-oxide 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)propylsulfonyl)-2,3-dichlorobenzeneacetic acid 4- (3- (4-Acetyl-3-hydroxy-2-propylphenoxy) -2- hydroxypropylthio) -2,3-dichlorobenzeneacetic acid S-oxide 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2 hydroxypropylsulfonyl) -2,3-dichlorobenzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)propyl thio) -2-fluorobenzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2 hydroxypropylthio)-2-fluorobenzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2 hydroxypropylthio)-2-fluorobenzeneacetic acid-S-oxide 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2 hydroxypropylsulfonyl) -2-fluorobenzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2 propenylsulfonyl)-2-fluorobenzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)propyl thio)-3-fluorobenzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2 hydroxypropylthio)-3-fluorobenzeneacetic acid 4- (3- (4-Acetyl-3-hydroxy-2-propylphenoxy) - propylthio)-3-chlorobenzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propyl thio)-3-chlorobenzeneacetic acid-S-oxide 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propyl sulfonyl)-3-chlorobenzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2 hydroxypropylthio) -3-chlorobenzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2 hydroxypropylthio)-3-chlorobenzeneacetic acid-S oxide 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2 hydroxypropylsulfonyl) -3-chlorobenzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propyl thio)benzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propyl sulfonyl)-benzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-methylpropylthio)-benzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2hydroxypropylthio)-benzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2hydroxypropylthio)-3-fluorobenzoic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2hydroxypropylthio)-3-fluorobenzoic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2hydroxypropylsulfonyl)-3-fluorobenzoic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propylthio)-3-fluorobenzoic acid-S-oxide, methyl ester 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propylsulfonyl)-3-fluorobenzoic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propylcyanamido)-benzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propylthio)delta-hydroxybenzenebutanol 4-(3-(4-Acetyl-3-hydroxy-2-propyl-phenoxy)-propylsulfonyl)-delta-hydroxybenzenebutanol 4- (3- (4-acetyl-3-hydroxy-2-propylphenoxy) - propylthio)-alpha-hydroxybenzeneacetic acid 4- (3- (4-acetyl-3-hydroxy-2-propylphenoxy) - propylsulfonyl)-alpha-hydroxybenzeneacetic acid 4- (3- (4-acetyl-3-hydroxy-2-propylphenoxy) - propyloxyr-alpha-hydroxybenzeneacetic acid 4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)propylthio)-3-bromo-alpha-hydroxybenzeneacetic ac d 4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy) - propylthio)-3-fluoro-alpha-hydroxybenzeneacetic acid 2-(4-(3-acetyl-3-hydroxy-2-propylphenoxy)propyloxy) -alpha-hydroxybenzeneacetic acid Methyl 4-(4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl thio)phenyl)-3-methyl-3(E)-butenoate 4-(4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl thio)phenyl)-3-methyl-3(E)-butenoic acid Methyl 4-(4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl thio)phenyl)-3-methyl-3(Z)-butenoate 4-(4 -(3 -(4-acetyl-3-hydroxy-2-propylphenoxy)propyl- thio)phenyl)-3-methyl-3(Z)-butenoic acid. 5. A pharmaceutical composition useful for antagonizing leukotrienes in mammals, especially humans, containing an effective amount of a compound as claimed in Claim 1 and a pharmaceutically acceptable carrier. 6. A compound as claimed in Claim 1 for use in antagonizing leukotriene action in a mammal. 7. A method of preparing a compound as claimed in Claim 1 that comprises condensing a compound of the formula: EMI57.1 where Q is EMI57.2 EMI58.1 with a compound of the Formula EMI58.2 wherein R, R1, R2, R3, R', Y', Y and m have the meaning given in Claim 1, and X is halogen. 8. A method of preparing a compound of Claim 1 which comprises condensing a compound of the Formula: EMI58.3 wherein Q is EMI58.4 EMI59.1 with a compound of the Formula EMI59.2 wherein R, R1, R2, R3, R', Y', Y and m have the meaning given in Claim 3, and X is halogen. 9. A method of preparing a compound of Claim 1 which comprises condensing a compound having one of the following Formulae EMI59.3 EMI60.1 with a compound of the Formula EMI60.2 wherein R1, R2, R3, R, R', Y, Y' and m are as defined in Claim 1, and X is halogen. 10. A method of preparing a compound of Claim 1 which comprises condensing a compound of the Formula: EMI61.1 with a compound of the Formula EMI61.2 wherein R, R1, R2, R3, R;, Y', Y and m have the meanina given in Claim 3, and X is halogen. 11. A compound having one of the following Formulae: EMI62.1 wherein Y', R, R1, R2, R' and m have the meaning given in Claim 1, and X is halogen. 12. A comppund having one of the following Formulae: EMI62.2 EMI63.1 wherein Y', R, R1, R2, R' and m have the meaning given in Claim 3, and X is halogen.

Inventors: BELANGER, PATRICE C., FORTIN, REJEAN, GUIDON, YVAN, ROKACH, JOSHUA, YOAKIM, CHRISTIANE, GUINDON, YVAN
Applicants: MERCK FROSST CANADA INC.
Application year: 1983
Main classification: C07C149
IPC codes: A61K31, C07C381, C07C45, A61P29, C07C317, C07C323, A61P11, C07C59, A61P9, A61P43, C07C239, C07C67, C07C261, C07C313, C07C49, C07C51, C07C325, A61P37