NZ248350A

NZ248350A - Isobutyl-substituted methanesulphonyl-quinolyl- methoxyphenyl-cycloalkylacetamide derivatives and pharmaceutical compositions

Info

Publication number: NZ248350A
Application number: NZ248350A
Authority: NZ
Inventors: Siegfried Raddatz; Klaus-Helmut Mohrs; Michael Matzke; Romanis Fruchtmann; Reiner Muller-Peddinghaus; Armin Hatzelmann
Original assignee: Bayer Ag
Priority date: 1992-08-12
Filing date: 1993-08-09
Publication date: 1994-12-22
Also published as: FI933529A; IL106623A0; MX9304608A; NO179948C; NO932731D0; CZ163693A3; MY108716A; SK86693A3; ZA935828B; AU669913B2; PL300025A1; PL174102B1; FI933529A0; CN1039998C; CA2103600A1; NO179948B; RU2103261C1; AU4425593A; EP0582916A1; HU9302320D0

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £48350 Patents Form 5 Priority Daiefs}: Complete Specification Filed: C'aQs: Publication Date: , .3 .? ,?£?. I??!1....... P.O. Journal, No: .... tl ^ *■*., SrT "™* p~V »; paps /C"i WJ UI iA\f tf l a ^ y 3 NEW ISOBUTYL-SUBSTITUTED METHANESULPHQNYL-OUINOLYL-METHOXYPHENY L-CYCLO ALK YL A CETA MI PES We, BAYER AKTIENGESELLSCHAFT, a Company registered under the laws of the Federal Republic of Germany, of Leverkusen, Germany do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: - - 1 - (Followed by 1A) tn £/?« J The invention relates to new isobutyl-substituted meth-anesulphonyl-quinolylmethoxyphenyl-cycloalkylacetamides, a process for their preparation and their use in medicaments. Substituted 4-(quinolin-2-yl-methoxy)phenylacetic acid derivatives and a-substituted 4-(quinolin-2-yl-methoxy)-phenylacetic acid derivatives have been disclosed in EP 344,519 (US 4,970,215) and EP 339,416. The present invention relates to new isobutyl-substituted 10 methanesulphonyl-quinolylmethoxyphenyl-cycloalkylacet- amides of the general formula (I) in which 0^nh-s02-ch3 (I) R represents cyclohexyl, 15 in the form of the racemate and of the enantiomers as well as the two enantiomers of the compounds of the in. A B8 - 1 A,- formula (I), in which R1 represents cyclopentyl or cyclo-heptyl and their salts. In the context of the present invention, physiologically acceptable salts are preferred. Physiologically acceptable salts of the compounds according to the invention can be salts of the substances according to the invention with mineral acids, carboxylic acids or sulphonic acids. Particularly preferred salts, for example, are those with hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, ethanesulphonic acid, toluenesulphonic acid, benzenesulphonic acid, naphthalenedisulphonic acid, acetic acid, propionic acid, lactic acid, tartaric acid, citric acid, fumaric acid, maleic acid or benzoic acid. Salts in the context of the present invention are additionally metal salts, preferably of the univalent metals, and the ammonium salts. Preferred alkali metal salts are those such as, for example, sodium, potassium and ammonium salts. The compounds of the general formula (I) according to the invention are prepared by reacting the carboxylic acids of the general formula (II) 483 5 C (ii) R1 has the abovementioned meaning, if appropriate with prior activation, with methanesul-5 phonamide of the formula (III) H2N-S02-CH3 (III) in inert solvents, in the presence of a base and/or catalyst, and in the case of the enantiomers, either employing the 10 enantiomerically pure acids (II) directly or resolving the racemates (I) according to customary methods. The enantiomers are preferably resolved by column chromatography . The process according to the invention can be illustrated 15 by way of example by the following reaction scheme: A 29 - 3 - 1) Mesyl chloride 2) H2N-S02CH3 ►- Triethylamine DMAP C0-NH-S02-CH3 The sulphoamidation is in general carried out in inert solvents in the presence of a base and of a dehydrating agent. Suitable solvents in this connection are inert organic solvents which do not change under the reaction conditions. These include halogenohydrocarbons such as dichlo-romethane, trichloromethane, tetrachloromethane, 1,2-dichloroethane, trichloroethane, tetrachloroethane, 1,2-dichloroethylene or trichloroethylene, hydrocarbons such as benzene, xylene, toluene, hexane or cyclohexane or mineral oil fractions, nitromethane, dimethylformamide, acetonitrile or hexamethylphosphoramide. It is also possible to employ mixtures of the solvents. Dichloromethane is particularly preferred. Suitable bases for the sulphoamidation are the customary basic compounds. These preferably include alkali metal and alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide or barium hydroxide, alkali metal hydrides such as sodium hydride, alkali metal or alkaline earth metal carbonates such as sodium carbonate or potassium carbonate, or alkali metal alkoxides such-as, for example, sodium methoxide or sodium ethoxide, potassium methoxide or potassium ethoxide or potassium tert-butoxide, or organic amines such as benzyltrimethylammonium hydroxide, tetra-butylammonium hydroxide, dimethylaminopyridine, pyridine, triethylamine or N-methylpiperidine. Suitable dehydrating reagents are carbodiimides such as, for example, diisopropylcarbodiimide, dicyclohexylcar-bodiimide or N-(3-dimethylaminopropyl)-N'-ethylcarbodi-imide hydrochloride or carbonyl compounds such as car-bonyldiimidazole or 1,2-oxazolium compounds such as 2-ethyl-5-phenyl-l,2-oxazolium-3-sulphonate or propanephosphonic anhydride or isobutyl chloroformate or benzotriazolyloxy-tris-(dimethylamino)phosphonium hexafluorophosphate or diphenyl phosphoramidate or methanesulphonyl chloride, if appropriate in the presence of bases such as triethylamine or N-ethylmorpholine or N-methylpiperidine or dicyclohexylcarbodiimide and # N-hydroxysuccinimide. When carrying out the sulphoamidation, the base is in general employed in an amount from 1 to 3 mol, preferably from 1 to 1.5 mol, relative to 1 mol of the carboxylic 5 acid (II). In the case of reaction via the mixed anhydride, di-methylaminopyridine is preferably employed as the catalyst. The catalyst is in general -employed in catalytic to 10 equimolar amounts, preferably equimolar amounts. The sulphoamidation is in general carried out in a temperature range from 0°C to 150°C, preferably at 25°C to 40°C. The sulphoamidation is in general carried out at normal 15 pressure. However, it is also possible to carry out the process at reduced pressure or at elevated pressure (for example in a range from 0.5 to 5 bar). With the exception of the case R1 = cycloheptyl, the carboxylic acids of the general formula (II) are, as 20 actual substance representatives, in particular in enantiomerically pure form, new and can be prepared, for example, by either converting compounds of the general formula (IV) or (IVa) t-0. 'ch-rj I CO2R7 (IV) or t'-o. 'ch2 I co2r2' (IVa) in which R1 has the abovementioned meaning, T and T' are identical or different and represent a hydroxyl protective group such as benzyl or tert-butyl and R2 and R2' are identical or different and denote Cj-C*- alkyl, after removal of the protective group with 2-halogenomethylguinoline of the formula (V) in which V represents halogen, preferably chlorine or bromine, in inert solvents by etherification into the compounds of the general formula (VI) or (Via) (VI) or CH-R, CO2R2 in which (Via) R1, R2 and R2' have the abovementioned meaning, and in the case of the compounds of the general formula (Via), subjecting these in a 2nd step to an alkylation with compounds of the general formula (VII) Rx-W (VII) in which R1 has the abovementioned meaning and W represents chlorine, bromine or iodine, in inert solvents, and then hydrolysing the esters by customary methods, 10 15 £ 20 and in the case of the enantiomers, resolving the racemic acids by column chromatography on chiral acids according to a customary method. The protective groups are removed from the corresponding ethers (IV) and (IVa) by a customary method, for example by hydrogenolytic cleavage of the benzyl ethers in the abovementioned inert solvents in the presence of a catalyst using hydrogen gas. The etherification can be carried out in inert organic solvents, if appropriate in-the presence of a base. Solvents for the etherification can be inert organic solvents which do not change under the reaction conditions. These preferably include ethers such as, for example, dioxane, tetrahydrofuran or diethyl ether, halogenohydrocarbons such as dichloromethane, trichloro-methane, tetrachloromethane, 1,2-dichloroethane or trichloroethylene, hydrocarbons such as benzene, xylene, toluene, hexane, cyclohexane or mineral oil fractions, nitromethane, dimethylformamide, acetonitrile, acetone or hexamethylphosphoramide. It is also possible to employ mixtures of the solvents. Bases employed for the etherification can be inorganic or organic bases. These preferably include alkali metal hydroxides such as, for example, sodium hydroxide or potassium hydroxide, alkaline earth metal hydroxides, such as, for example, barium hydroxide, alkali metal carbonates such as sodium carbonate or potassium JPi S9 £■»» - 10 - carbonate, _ alkaline earth metal carbonates such as calcium carbonate, or organic amines (trialkylfCi-C6)amines) such as triethylamine, or heterocycles such as pyridine, methylpiperidine, piperidine or morpholine. It is also possible to employ as bases alkali metals such as sodium and their hydrides, such as sodium hydride. The etherification is in general carried out in a temperature range from 0°C to +150°C, preferably from +10°C to +100°C. The etherification is in general carried out at normal pressure. However, it is also possible to carry out the process at reduced pressure or elevated pressure (for example in a range from 0.5 to 5 bar). In general, 0.5 to 5 mol, preferably 1 to 2 mol of halide (V) are employed, relative to 1 mol of the reactant. The base is in general employed in an amount from 0.5 to 5 mol, preferably from 1 to 3 mol, relative to the halide. The compounds of the general formulae (IV) and (IVa) are known per se or can be prepared by a customary method. The compounds of the general formula (V) and their preparation are also known. Suitable solvents for the processes according to the invention and for the alkylation are customary organic solvents which do not change under the reaction conditions. These preferably include ethers such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether, 5 or hydrocarbons such as benzene, toluene, xylene, hexane, cyclohexane or mineral oil fractions, or halogenohydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane, dichloroethylene, trichloroethylene or chlorobenzene, or ethyl acetate, or triethylamine, 10 pyridine, dimethyl sulphoxide, dimethylformamide, hexa-methylphosphoramide, acetonitrile, acetone or nitrometh-ane. It is also possible to use mixtures of the solvents mentioned. Dichloromethane is preferred. The alkylation is carried out in the abovementioned 15 solvents at temperatures from 0°C to +150°C, preferably at room temperature to +100°C, and at normal pressure. The compounds of the general formula (III) are known per se. As actual substance representatives, the compounds of the 20 general formula (VI) are new in some cases and can be prepared as described above. The racemates are in general resolved by column chromatography on chiral HPLC columns using solvent mixtures such as, for example, n-heptane/2-propanol or via diastereo-25 meric esters. The new N-methanesulphonyl-2-[3-isobutyl-3-(quinolin-2-yl-methoxy)phenyl]-2-cycloalkylacetamides according to the invention can be employed as active compounds in medicaments. The substances can act as inhibitors of enzymatic reactions in the context of arachidonic acid metabolism, in particular of lipoxygenase. They are thus preferably suited to the treatment of and prevention of diseases of the airways such as allergies/asthma, bronchitis, emphysema, shock lung, pulmonary hypertension, inflammations/rheumatism and oedemas, thromboses and thromboembolisms, ischaemia (peripheral, cardiac and cerebral circulatory disorders), cardiac and cerebral infarcts, angina pectoris, arteriosclerosis, in tissue transplants, dermatoses such as psoriasis, inflammatory dermatoses and for cytoprotection in the gastrointestinal tract. The phenyl-substituted quinolines according to the invention can be used both in human medicine and in veterinary medicine. The pharmacological actions of the substances according to the invention are determined by the following method: As a measure of lipoxygenase inhibition, the release of leucotriene B4 (LTB4) in polymorphonuclear human leucocytes (PMN) was determined after addition of substances and Ca ionophore by means of reverse phase HPLC according to Borgeat, P. et al., Proc. Nat. Acad. Sci., 76. 2148-2152 (.1979). Lipoxygenase inhibition (human PMNL) Ex. No 1 6 7 IC50[mol/l] 5.2 x 10'8 5.8 x 10"8 7.0 x 10"8 The present invention also includes pharmaceutical preparations which, apart from inert, non-toxic, pharmaceutical^ suitable auxiliaries and excipients, contain one or more compounds of the general formula (I), or which consist of one or more active compounds of the formula (I), as well as processes for the production of these preparations. The active compounds of the formula (I) should be present in these preparations in a concentration from 0.1 to 99.5% by weight, preferably from 0.5 to 95% by weight of the total mixture. Apart from the active compounds of the formula (I), the pharmaceutical preparations can also contain other pharmaceutical active compounds. The abovementioned pharmaceutical preparations can be prepared by known methods in a customary manner, for example using the auxiliary(ies) or excipient(s). In general,. it has proven advantageous to administer the active compound(s) of the formula (I) in total amounts from about 0.01 to about 100 mg/kg, preferably in total amounts from about 1 mg/kg to 50 mg/kg of body weight every 24 hours, if appropriate in the form of several individual doses, to achieve the desired result. However, it may sometimes be advantageous to deviate from the amounts mentioned, mainly depending on the type and on the body weight of the subject to be treated, on individual behaviour towards the medicament, the nature and severity of the disease,-the method of preparation and administration, and the time or interval at which administration takes place. Starting Compounds Example I Methyl 2-[3-isobuty1-4-(quinolin-2-yl-methoxy)phenyl]-2-cyclohexyl-acetate C02CH3 f f\ r-7 {£ A 445*1 :< {J 10 15 12 g (0.033 mol) of methyl 2-[3-isobutyl-4-(quinolin-2-yl-methoxy)phenylacetate and 6.52 g (0.04 mol) = 4.9 ml of cyclohexyl bromide are dissolved in 36 ml of DMF and cooled to 0°C under an argon atmosphere. 4.88 g (0.04 mol) of potassium tertiary butoxide, dissolved in 80 ml of DMF, are added dropwise to this mixture with stirring. After a reaction time of about 2 h, the temperature is allowed to rise to RT, and the mixture is acidified with 2N hydrochloric acid and concentrated to dryness in vacuo. The residue which remains is stirred with 100 ml of dichloromethane and 50 ml of water, the organic phase is separated off, dried using~Na2S0^ and concentrated to a small volume in vacuo, and the residue which remains is separated by column chromatography (silica gel 60, eluent: dichloromethane/ethyl acetate = 100:2). Yield: 13 g (88.4% of theory), slightly yellowish oil Example II 2-[3-Isobutyl-4- (quinolin-2-yl-methoxy) phenyl ]-2-cyclo-hexyl-acetic acid 20 co,h LL A cd aa» - 16 10.2 g (0.0236 mol) of the compound from Example I are taken up in 70 ml of 2-propanol and heated to boiling overnight with 50 ml of IN sodium hydroxide solution. After cooling, the mixture is neutralised using 50 ml of 5 IN hydrochloric acid. The precipitate obtained is filtered off with suction, washed and dried, and then recrystallised from diisopropyl ether. Yield: 9.5 g (96.3% of theory), colourless crystals M.p.: 130°C 10 Example III and Example IV (+)-2-[3-Isobutyl-4-(quinolin-2-yl-methoxy)phenyl]-2-cyclohexyl-acetic acid (Example III) (-)-2-[3-Isobutyl-4-(quinolin-2-yl-methoxy)phenyl]-2-cyclohexyl-acetic acid (Example IV) The title compounds are obtained by resolution of the racemate (Example II) by means of chromatographic resolution on chiral columns. (+)-Enantiomer: spec, rotn.: 17.96° (CHC13) (Example III) mol. rotn.: 77.41° (-)-Enantiomer: spec, rotn.: -18.86° (CHC13) (Example IV) mol. rotn.: -81.28° Example V Methyl 2-[3-isobutyl-4-(quinolin-2-yl-methoxy)phenyl]-2-cycloheptyl acetate 10 g (0.0275 mol) of methyl 2-[3-isobutyl-4-(quinolin-2-yl-methoxy)phenylacetate are reacted with 10.04 g (0.055 mol) of cycloheptyl bromide and 6.17 g (0.055 mol) of potassium tertiary butoxide to give the title compound in analogy to the procedure of Example I. Yield: quantitative, yellow-brown oil Example VI 2 - [ 3 -1 sobuty 1- 4 - (quinolin-2 -yl-methoxy) phenyl ] -2-cyclo-heptylacetic acid C02CH3 The title compound is prepared from the compound of Example V and 30 ml of IN sodium hydroxide solution with subsequent acidification in analogy to the procedure of Example II. Yield: 11.3 g (92.3% of theory), colourless crystals M.p.: 112°C Example VII and Example VIII (+)-2-[ 3-Isobutyl-4-(quinolin-2-yl-methoxy) phenyl ] -2-10 cycloheptylacetic acid (Example VII) (-) -2- [ 3-Isobuty 1-4- (quinolin-2-yl-methoxy) phenyl ] -2-cycloheptylacetic acid (Example VIII) ijju fli SO »» 19 co2h The title compounds are prepared from the racemate (Example VI) by chromatographic resolution on HPLC-H 1050 Chiralpak AS in a solvent mixture of 96% n-heptane and 4% 5 of a mixture of 2-propanol which contains 1% water and 0.2% trifluoroacetic acid. (+)-Enantiomer: spec, rotn.: 15.72°, solvent CHC13, Example VII mol. rotn.: 69.96° 10 (-)-Enantiomer: spec, rotn.: -18.7°, solvent CHC13, Example VIII mol. rotn.: -86.19° Example IX Methyl 2-[3-isobutyl-4-(quinolin-2-yl-methoxy)phenyl]-2 cycloheptylacetate The title compound is prepared from 10 g (0.0275 mol) of methyl 2-[3~isobutyl-4-(quinolin-2-yl-methoxy)phenyl]-acetate, 8.2 g (0.055 mol) of cyclopentyl bromide and 6.17 g (0.055 mol) of potassium tertiary butoxide in analogy to the procedures of Examples I and V. Yield: quantitative, yellow-brown oil Example X 2- [ 3-Isobutyl-4- (quinolin-2-yl-methoxy) phenyl] -2-cyclo-pentylacetic acid c02ch3 A a 7 £ n £•!■ O) r ! i ? j co2h The title compound is prepared from the compound of Example IX by hydrolysis using 30 ml of sodium hydroxide solution and subsequent acidification in analogy to the 5 procedures of Examples II and VI. Yield: 10.5 g (91.5% of theory), slightly yellowish crystals M.p.: 120°C Examples XI and XII 10 ( + ) -2-[ 3-1 sobuty 1-4- (quinolin-2-yl-methoxy) phenyl ]-2-cyclopentylacetic acid (Example XI) (-) -2-[3-Isobutyl-4-(quinolin-2-yl-methoxy) phenyl]-2-cyclopentylacetic acid (Example XII) Ji 20 22 - co2h In analogy to the procedure of Examples VII and VIII, the title compounds are obtained by chromatographic resolution of the compound of Example X. 5 (+)-Enantiomer: spec, rotn.: 44.56° (THF), Example XI mol. rotn.: 185.84° (-)-Enantiomer: spec, rotn.: -41.07° (THF), Example XII mol. rotn.: -171.28° Example XIII 10 N-Methanesulphonyl-2- [ 3-isobutyl-4-(quinolin-2-yl-meth-oxy)phenyl]-2-cycloheptylacetamide cr nh-so2-ch3 iia h DP - 23 - /. o T? K A -4 o ') -' 4 ? 2 g (0.0045 mol) of the compound from Example VI are suspended in 20 ml of dried THF under argon and treated with 1.82 g (0.018 mol) of triethylamine (d = 0.73). A clear solution is formed. 1.14 g (0.01 mol) of mesyl 5 chloride (d = 1.48) are added dropwise with cooling in an ice bath/ the mixture is stirred at this temperature for a further 15 min and 1.52 g (0.016 mol) of methanesul-phonamide and 1.1 g (0.009 mol) of dimethylaminopyridine, dissolved in 10 ml of dry THF, are then added dropwise 10 with stirring. The mixture is allowed to react overnight, during the course of which the temperature rises to RT. The mixture is poured into toluene and extracted with water and dilute acetic acid. The organic phase is separated off, dried using Na2S04 and concentrated in 15 vacuo to a small volume, and the pale brown oil which remains (2.42 g) is subjected to column chromatography (silica gel 60, eluent: toluene/ethyl acetate/glacial acetic acid = 8:2:1). 1.75 g (74.6% of theory) of a colourless product (amoc-20 phous) are obtained. Preparation Examples Example 1 N-Methanesulphonyl-2- [3-isobutyl-4-(quinolin-2-yl-meth-oxy)phenyl]-cyclohexylacetamide Tn T) 19 1AA - 24 - 24 0 10 O^NH-S02-CH3 In analogy to the procedure of Example XIII, the title compound is prepared from J". 5 g (0.008 mol) of the compound from Example II, 1 g (0.008 mol) of mesyl chloride, 0.912 g of methanesulphonamide, 1.62 g (0.016 mol) of triethylamine and 0.98 g (0.008 mol) of dimethylaminopyridine . Yield: 3.48 g (84.9% of theory), colourless amorphous powder M.p.: 163-170°C Example 2 and Example 3 (+)-N-Methanesulphonyl-2-[3-isobutyl-4-(quinolin-2-yl-methoxy)phenyl]-2-cyclohexylacetamide (Example 2) 15 (-)-N-Methanesulphonyl-2-[ 3-isobutyl-4-(quinolin-2-yl-methoxy)phenyl]-2-cyclohexylacetamide (Example 3) JL 11) 739 - 25 - 83 5 0 10 O^NH-S02-CH3 The two enantiomers are obtained by column chromatographic resolution of the compound from Example 1 on HPLC-HP 1050 Chiralcel OD in an eluent mixture of 86% n-heptane and 14% of a 2-propanol mixture which contains 1% water + 0.2% trifluoroacetic acid. (+)-Enantiomer: spec, rotn.: +32.15° (CHC13) Example 2 mol. rotn.: +163.32° (-)-Enantiomer: spec, rotn.: -28.96° (CHC13) Example 3 mol. rotn.: -147.12° The pure enantiomers shown in Table 1 can either be prepared in analogy to the procedures of Examples 2 and 3 via resolution of the racemate or by use of the corresponding enantiomerically pure carboxylic acids. -t» * •>«» 0,30 - 26 - </div>

Claims

<div class="application article clearfix printTableText" id="claims"> 4t\ T w*;Bod;Table 1:;Ex. No. R1 Enantiomer mol. rotn. spec. rotn. 5 4;5;6;10;7;( + );(-);( + ) +147.99° +28.35°;(CHC13) (CHCI3);(-) -169.91° -32.55°;(CHCI3) (CHC13);248350;WHAT WE CLAIM IS:;1.;Isobutyl -substituted methanesulphonyl-quinolyl-;methoxyphenyl-cycloalkylacetamides of the formula in which;R1 represents cyclohexyl in the form of the racemate and of the enantiomers as well as the enantiomers if;R1 represents cyclopentyl or cycloheptyl and their salts.;2. Racemate, (+)-enantiomer and (-)-enantiomer of the o^nh-so2-ch3;* <•>, wci 4 H o t) I compound of the formula 0^nh-s02-ch3 and its salts. 3. (+)-Enantiomer and (-)-enantiomer of the compound of the formula o^nh-so2-ch3 and its salts. fca A BO - 29 - 248350 (+)-Enantiomer and (-)-enantiomer of the compound of the formula and its salts. Isobutyl -substituted methanesulphonyl-quinolyl-methoxyphenyl-cycloalkylacetamides according to Claim 1 for therapeutic use. Process for the preparation of an isobutyl-substituted methanesulphonyl-quinolylmethoxy-cyclo-alkylphenylacetamide according to Claim 1, characterised in that a carboxylic acid of the general formula (II) - 30 - 248350 in which R1 has the abovementioned meaning, is reacted, if appropriate with prior activation, with methane sulphonamide of the formula (III) H2N-S02-CH3 (III) in at least one inert solvent, in the presence of a base and/or catalyst, and in the case of an enantiomer, either the enantiomerically pure acid (II) is employed directly or a racemate (I) is resolved according to customary methods. Process according to Claim 6, characterised in that the enantiomers are resolved by column chromato-graphy. Medicaments containing at least one 248350 isobutyl-substituted methanesulphonyl-quinolylmethoxyphenyl-cycloalkylacetamide according to Claim 1. 9. Use of isobutyl-substituted methanesulphonyl-quin-olylmethoxyphenyl-cycloalkylacetamides according to Claim 1 for the production of medicaments. 10. Use according to Claim 9 for the production of lipoxygenase-inhibiting medicaments. 11. An isobutyl-substituted m-ethanesulphonyl-quinolyl-methoxyphenyl-cycloalkylacetamide according to claim 1 substantially as herein described or exemplified. 12. Racemate, (+)-enantiomer and (-)-enantiomer of the compound of the formula and its salts, according to claim 2 substantially as herein described or exemplified. 13. (+)-Enantiomer and (-)-enantiomer of the compound of the formula and its salts according to claim 3 or 4 substantially as herein described or exemplfied. 14. A process according to claim 6 substantially as herein described or exemplified. BAYER AKTIENGESELLSCHAFT By Their Attorneys HENRY HUGHES LTD Per: </div>