GB2356138A

GB2356138A - Use of substituted 4-(quinolin-2-yl-methoxy)phenyl-acetic acid derivatives for the treatment of diseases

Info

Publication number: GB2356138A
Application number: GB9926983A
Authority: GB
Inventors: Bill Taylor
Original assignee: Bayer AG
Current assignee: Bayer AG
Priority date: 1999-11-15
Filing date: 1999-11-15
Publication date: 2001-05-16
Also published as: AU1518901A; WO2001035960A1; GB9926983D0

Abstract

Use of substituted 4-(quinolin-2-yl-methoxy)phenyl-acetic acid derivatives of the formula <EMI ID=1.1 HE=43 WI=108 LX=643 LY=874 TI=CF> <PC>R<SP>1</SP> represents a group of the formula <EMI ID=1.2 HE=16 WI=57 LX=542 LY=1412 TI=CF> <PC>wherein<BR> Y represents a group of the formula <EMI ID=1.3 HE=18 WI=20 LX=772 LY=1819 TI=CF> <PC>Z represents norbornyl, or represents a group of the formula <EMI ID=1.4 HE=18 WI=92 LX=667 LY=2096 TI=CF> <PC>and<BR> A and B are identical or different and denote hydrogen, lower alkyl or halogen,<BR> and salts thereof for the treatment of glomerular nephritis, lung cancer, multiple sclerosis, ocular inflammation, osteoporosis, reperfusion injury and tinnitus.

Description

2356138 Use of substituted 4-(quinolin 2-yl-methoxy)phenyl-acetic acid

derivatives for the treatment of diseases The invention relates to the use of substituted 4-(quinolin-2-yl- methoxy)phenylacetic acids, esters and amides in medicaments for the treatment of glomerular nephritis, lung cancer, multiple sclerosis, ocular inflammation, osteoporosis, reperfusion injury and tinnitus.

Substituted 4-(quinolin-2-yl-methoxy)phenylacetic acid derivatives are known from EP-A-344 519. For 2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl- acetic acid, myocardial protection has been described (Rossini, G. et al., J.P.E.T. 276: 335-41, 1996). It has now been found that substituted 4-(quinolin-2-ylmethoxyphenyl acetic acids and esters and amides thereof, of the general formula (I) B A 0 I Y-Z 0 Ri in which Ri represents a group of the formula 2 -OR 2 or -N R wherein R2 and R3 are identical or different and represent hydrogen, alkyl, aryl, aralkyl or a group of the formula R 4 R 4 1 5 1 5 -CH-COI 2 R -UH-UHF-OR, R 4 R 4 1 6 1 7 -CH-OR CH R 0 Y 0 0 wherein R4 represents hydrogen, alkyl, aralkyl or aryl, which can optionally be substituted by hydroxyl, carboxyl, alkoxy carbonyl, alkylthio, heteroaryl or carbamoyl, R5 represents hydrogen, alkyl, aryl or aralkyl, R6 represents a group of the formula -COR5 or -C02R5, wherein R5 has the abovementioned meaning, R7 represents hydrogen, alkyl or aryl, Y represents a group of the formula 8 R (-CH) n wherein R8 represents hydrogen, alkyl or aryl and n denotes a number from 0 to 5, z represents norbomyl, or represents a group of the formula CH R io C 10 ,- '.R R 9 or _C11_1 - IR 9 (C)M (C)M wherein R9 and RIO are identical or different and denote hydrogen, alkyl or aryl, or 10 R9 and RIO can together form a saturated carbocyclic ring having up to 6 carbon atoms and In denotes a number from 1 to 6, and 15 A and B are identical or different and denote hydrogen, lower alkyl or halogen, and salts thereof, can be used for the treatment and prevention of glomerular nephritis, lung cancer, multiple sclerosis, ocular inflammation, osteoporosis, reperfusion injury and tinnitus. Alkyl in general represents a straight- chain or branched hydrocarbon radical having I to 12 carbon atoms. Lower alkyl having I to about 6 carbon atoms is preferred. 25 Examples which may be mentioned are methyl, ethyl, propyl, isopropyl, butyl, tert.butyl, isobutyl, pentyl, isopentyl, hexyl, isohexyl, heptyl, isoheptyl, octyl and isooctyl.

Haloge in general represents fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine. Halogen particularly preferably represents fluorine or chlorine.

Aryl in general represents an aromatic radical having 6 to about 12 carbon atoms. Preferred aryl radicals are phenyl, naphtyl and biphenyl. Aralkyl in general represents an aryl radical which has 7 to 14 carbon atoms and is bonded via an alkylene chain. Aralkyl radicals having I to 6 carbon atoms in the 10 aliphatic part and 6 to 12 carbon atoms in the aromatic part are preferred. The following aralkyl radicals may be mentioned as examples: benzyl, naphtylmethyl, phenethyl and phenylpropyl. Alkylthio in general represents a straight-chain or branched hydrocarbon radical 15 which has I to 12 carbon atoms and is bonded via a sulphur atom. Lower alkylthio having I to about 6 carbon atoms is preferred. An alkylthio radical having I to 4 carbon atoms is particularly preferred. Examples which may be mentioned are methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, pentylthio, isopentylthio, hexylthio, isohexylthio, heptylthio, isoheptylthio, octylthio and iso20 octylthio.

Alkoxycarbonyl can be represented, for example, by the formula -C-OAlkyl I I 0 25 Alkyl in this formula represents a straight-chain or branched hydrocarbon radical having 1 to 12 carbon atoms. Lower alkoxycarbonyl having I to about 6 carbon atoms in the alkyl part is preferred. Alkoxycarbonyl having I to 4 carbon atoms in the alkyl part is particularly preferred. The following alkoxycarbonyl radicals may be mentioned as examples: methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl and isobutoxycarbonyl.

Heteroaryl in the context of the abovementioned definition in general represents a 5 to 6- membered aromatic ring which can contain oxygen, sulphur and/or nitrogen as hetero atoms and onto which a further aromatic ring can be fused. 5- and 6 membered aromatic rings which contain an oxygen, a sulphur and/or up to 2 nitrogen atoms and which are optionally benzo-fused are preferred. Particularly preferred heteroaryl radicals which may be mentioned are: thienyl, ftiryl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, quinolyl, isoquinolyl, quinazolyl, quinoxalyl, thiazolyl, benzothiazolyl, isothiazolyl, oxazolyl, benzoxazolyl, isoxazolyl, imidazolyl, benz imidazolyl, pyrazolyl, indolyl and isoindolyl.

Physiologically acceptable salts are preferred in the context of the present invention.

Physiologically acceptable salts of the substituted 4-(quinolin-2-ylmethoxy)phenyl- acetic acids esters and amides can be salts of the substances according to the invention with mineral acids, carboxylic acids or sulphonic acids. Particularly preferred salts are, for example, 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 furthermore salts of monovalent metals, such as alkali metals and ammonium salts. Sodium, potassium and ammonium salts are preferred.

Preferred compounds of the general formula (1) are those in which RI represents a group of the formula --OR 2 or N 11 R 3 wherein R2 and R3 are identical or different and represents hydrogen, lower alkyl, benzyl, phenyl or a group of the formula R4 R 4 -CH-CO 2R OR R 4 R 4 1 6 1 7 _U_I_U_R or LAI R 0 Y 0 0 wherein R4 represents hydrogen, lower alkyl, benzyl or phenyl, which can optionally be substituted by hydroxyl, lower alkoxycarbonyl, carboxyl, lower alkylthio, heteroaryl or carbamoyl, R5 represents hydrogen, lower alkyl, phenyl or benzyl, R6 represents a group of the formula -COR5 or -C02R5' wherein R5 has the above-mentioned meaning, and R7 represents hydrogen, lower alkyl or phenyl, Y represents a group of the formula R 8 1 (-UN)n wherein R8 represents hydrogen, lower alkyl or phenyl, and n denotes a number from 0 to 5, z represents norbornyl, or represents a group of the formula CH R jo C R 10 9 or -C 9 (C), (C) M wherein R9 and RIO are identical or different and denote hydrogen, lower alkyl or phenyl, or R9 and RIO can together form a saturated carbocyclic ring having, up to 6 carbon atoms and In denotes a number from 1 to 6, A and B are identical or different and denote hydrogen, methyl, ethyl, fluorine, chlorine or bromine, and salts thereof Particularly preferred compounds of the general formula (I) are those in which RI represents a group of the formula 2 -OR 2 or R 3 wherein R2 and R3 are identical or different and represents hydrogen, methyl, ethyl, propyl, isopropyl, butyl, tert.-butyl, phenyl or benzyl, or represents a group of the formula R4 R 4 1 5 1 5 -CH-CO 2R -CH-CHF-OR R 4 R 4 1 6 or U1 7 -L;ti-u-R R.

0 0 Y 0 wherein R4 represents hydrogen, methyl, ethyl, propyl, isopropyl, butyl, tert.-butyl, benzyl or phenyl, which can optionally be substituted by hydroxyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, carboxyl, methylthio, ethylthio, propylthio, imidazolyl or carbarnoyl, R5 represents hydrogen, methyl, ethyl, propyl, isopropyl, butyl, tert.-butyl, phenyl or benzyl, R6 represents a group of the formula -COR5 or -C02R5, wherein R5 has the abovementioned meaning, and R7 represents hydrogen, methyl, ethyl, propyl, isopropyl, butyl, tert.-butyl or phenyl, Y represents a group of the formula R 8 (-L;H)n wherein R8 represents hydrogen, methyl, ethyl, propyl, isopropyl, butyl, tert.- butyl or phenyl, and 15 n denotes a number from 0 to 5, z represents norbornyl or represents a group of the formula CH io C R 10 C::r q or -C 9 N-1 R _1 1::-R, (C)n, I C) wherein R9 and RIO are identical or different and denote hydrogen, methyl, ethyl, npropyl, iso-propyl, butyl or tert.-butyl, or 25 R9 and RIO can together form a saturated carbocyclic. ring having up to 6 carbon atoms and m denotes a number from I to 6, and A and B are identical or different and denote hydrogen, methyl, ethyl, fluorine or chlorine, and salts thereof Especially preferred compounds of the general formula (I) are those in which 10 RI represents a group of the formula 2 --OR 2 or - N R 3 wherein 15 R2 and R3 are identical or different and represents hydrogen or methyl, or represent hydrogen or methyl, or represent a group of the formula R4 R 4 1 5 1 5 -CH-C02R -CH-CHF-OR R 4 R 4 1 1 -L;H-U-R 6 or -UH R. 7 0 Y 0 0 wherein R4 represents hydrogen, methyl or phenyl, R5 represents hydrogen, methyl, ethyl, tert.-butyl or benzyl, R6 represents a group of the formula -COR5, wherein RS has the above-mentioned meaning, and R7 represents methyl, Y represents a group of the formula R 8 1 wherein R8 represents hydrogen or methyl, and n denotes the number 0 or 1, z represents norbornyl, or represents a group of the formula CH io C 10 C-4--R 9 or 9 (C)r" (C), wherein R9 and RIO are identical or different and denote hydrogen or methyl, or R9 and R 10 together form a cyclohexyl ring, and M denotes the number 1, 2, 3, 5 or 5, and A and B denote hydrogen or fluorine, and salts thereof 5 Most preferred in the compound (R)-(-)-2-[4-(quinolin-2-yl- methoxy)phenyl]-2cyclopentyl-acetic acid.

The compounds according to the invention can be in stereoisomeric forms which either behave as image and mirror image (enantiomers) or do not behave as image and mirror image (diastereomers).

The invention relates both to the antipodes and to the racemic forms as well as the diastereomer mixtures. The racernic forms, like the diastereomers, can be resolved into the stereoisomerically uniform constituents in a known manner (compare E.L.

Eliel, Stereochernistry of Carbon Compounds, McGraw Hill, 1962).

The following further active compounds may be mentioned specifically:

methyl 2-[4-(quinolin-2-yl-methoxy)phenyl]-3-cyclopropylpropionate methyl 2-[4-(quinolin-2-yl-methoxy)phenyl]-3-cyclohexylproprionate methyl 2-[4(quinolin-2-yl-methoxy)phenyl]-2-cyclopentylacetate methyl 2-[4-(quinolin2-yl-methoxy)phenyl]-2-cyclohexylacetate methyl 2-[4-(quinolin-2-ylmethoxy)phenyl]-2-cycloheptyl-acetate 25 2-[4-(quinolin-2-ylmethoxy)phenyl]-3-cyclopropyl-propionic acid 2-[4-(quinolin-2-ylmethoxy)phenyl]-3-cyclohexyl-propionic acid 2-[4-(quinolin-2-ylmethoxy)phenyl]-2-cyclopentyl-acetic acid 2-[4-(quinolin-2-ylmethoxy)phenyl]-2-cyclohexyl-acetic acid 2-[4-(quinolin-2-ylmethoxy)phenyl]-2-cycloheptyl-acetic acid 30 methyl 2-[4-(quinolin-2-ylmethoxy)phenyl]-2-(cyclohex-2-enyl)-acetate benzyloxycarbonylmethyl 2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopropyl- propionate benzyloxycarbonylmethyl 2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentylacetate 2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentylacetic acid methoxycarbonyl methylamide methyl 2-[4-(quinolin-2-yl-methoxy)phenyl]-2-(I-decalinyl)-acetate tert.-butoxycarbonylmethyl 2-[4-(quinolin-2-yl-methoxy)phenyl]-2cyclopentyl- acetate pivaloyloxymethyl 2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl- acetate methoxycarbonylmethyl 2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentylacetate 2-[4-(quinolin-2-yl-methoxy)phenyl]-2-(I-decalinyl)-acetic acid 2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl-acetic acidcarboxymethylamide sodium 2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl-acetate methyl 2-[4-(quinolin-2-yl-methoxy)phenyll-3-cyclopentylpropionate 2-[4-(quinolin-2-yl-methoxy)phenyl]-3-cyclopentyl-propionic acid 2-[4-(quinolin-2-yl-methoxy)phenyl]-2-(cyclohex-2-enyl)-acetic acid carboxymethyl 2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentylacetate methyl 2-[4-(6-fluoroquinolin-2-yl-methoxy)phenyl)-2-cyclopentylacetate 2-[4-(6-fluoroquinolin-2-yl-methoxy)phenyl)-2-cyclop.entylacetic acid methyl 2-[4-(quinolin-2-yl-methoxy)phenyl]-2-norbomyl-acetate 2-[4-(quinolin-2-yl-methoxy)phenyll-2-norbomyl-acetic acid 2[4-(quinolin-2-yl-methoxyphenyl]-2-cyclopentyl-acetic acid- [(L)-2hydroxy- 1 - phenylethyl]amide (both diastereomers) (+)-4-[2-(quinolin-2-yl-methoxyphenyl]-2-cyclopentylacetic acid and (-)-4-[2-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl-acetic acid.

The compounds of the general formula (I) are known from EP-A-344 519.

The acids, esters and amides according to the invention can be employed as active compounds in medicaments. The substances have an action in particular as inhibitors of enzymatic reactions in the context of arachidonic acid metabolism, in particular of 5-lipoxygenase.

The compounds according to the invention exhibit a good action following oral administration in lipoxygenase-sensitive test models and therefore are suitable for the treatment of glomerular nephritic, lung cancer, multiple sclerosis, ocular inflammation, osteoporosis, reperfusion injury and tinnitus.

For the obtainment of systemic activity the active compounds can be administered orally or parenterally.

For parenteral. administration, forms of administration to the mucous membranes (i.e.

buccal, lingual, sublingual, rectal, nasal, pulmonary, conjunctival or intravaginal) or into the interior of the body are particularly suitable. Administration can be carried out by avoiding absorption (i.e. intracardiac, intra-arterial, intravenous, intraspinal or intralumbar administration) or by including absorption (i.e. intracutaneous, subcutaneous, percutaneous, intramuscular or intraperitoneal administration).

For the above purpose the active compounds can be administered per se or in administration forms.

Suitable administration forms for oral administration are, inter alia, normal and enteric-coated tablets, capsules, coated tablets, pills, granules, pellets, powders, solid and liquid aerosols, syrups, emulsions, suspensions and solutions. Suitable administration forms for parenteral administration are injection and infusion solutions.

The active compound can be present in the administration forms in concentrations of from 0 - 100 % by weight; preferably the concentration of the active compound should be 0.5 - 90% by weight, i.e. quantities which are sufficient to allow the specified range of dosage.

15- The active compounds can be converted in the known manner into the abovementioned administration forms using inert non-toxic pharmaceutically suitable auxiliaries, such as for example excipients, solvents, vehicles, emulsifiers and/or dispersants.

The following auxiliaries can be mentioned as examples: water, solid excipients such as ground natural or synthetic minerals (e.g. talcum or silicates), sugar (e.g. lactose), non-toxic organic solvents such as paraffins, vegetable oils (e.g. sesame oil), alcohols (e.g. ethanol, glycerol), glycols (e.g. polyethylene glycol), emulsifying agents, dispersants (e.g. polyvinylpyrrolidone) and lubricants (e.g. magnesium sulphate).

In the case of oral administration tablets can of course also contain additives such as sodium citrate as well as additives such as starch, gelatin and the like. Flavour enhancers or colorants can also be added to aqueous preparations for oral administration.

For the obtainment of effective results in the case of parenteral administration it has generally proven advantageous to administer quantities of about 0.001 to 10 mg/kg, preferably about 0.01 to I mg/kg of body weight. In the case of oral administration the quantity is about 0.0 1 to 100 mg/kg, preferably about 0. 1 to 10 rng/kg of body weight.

It may nevertheless be necessary to use quantities other than those mentioned above, depending on the body weight concerned, the method of administration, the individual response to the active compound, the type of preparation and the time or interval of administration.

Example I

2-[4-(quinolin-2-yl-methoxy)phenyl]-3-cyclopropylpropionic acid Example 2

2-[4-(quinolin-2-yl-methoxy)phenyl]-3-cyclohexylpropionic acid Example 3 10 2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentylacetic acid Example 4 (use example) The release of leucotriene B4 (LTB4) from polymorphonuclear rat leucocytes (PN4N) following addition of substances and a Ca-ionophor was determined by means of reverse phase HPLC by the method of Borgeat, P. et al., Proc. Nat. Acad. Sci. (USA) 76, 2148-2152 (1979) as a measure of lipoxygenase inhibition.

The values achieved in this test with some compounds according to the invention are listed by way of example in Table 1:

Table I Lipoxygenase inhibition Example No. LO inhibition IC50 (ILM) 1 0.14 2 0.01 3 0.04 The compounds are known from EP-A-344 519.

Claims

Patent claims

I Use of a compound of the general formula (I) B A 0 N 0 RI in which RI represents a group of the formula --OR 2 or -N 10 wherein R2 and R3 are identical or different and represent hydrogen, alkyl, aryl, aralkyl. or a gToup of the formula R R 4 1 4 5 1 5 -CH-CO R -L;H-CH-OR 2 2 R 4 R 4 1 6 1 7 -L;H-0-R or -CH R 0 Y 0 0 wherein 18- R4 represents hydrogen, alkyl, aralkyl or aryl, which can optionally be substituted by hydroxyl, carboxyl, alkoxycarbonyl, alkylthio, heteroaryl or carbamoyl, R5 represents hydrogen, alkyl, aryl or aralkyl, R6 represents a group of the formula -COR5 or -C02R5, R7 represents hydrogen, alkyl or aryl, Y represents a group of the formula R 8 I (-L;tl)n wherein R8 represents hydrogen, alkyl or aryl and n denotes a number from 0 to 5, z represents norbornyl, or represents a group of the formula CH jo C 10 R 9 or -C IR 9 wherein 25 R9 and RIO are identical or different and denote hydrogen, alkyl or aryl, or R9 and RIO can together form a saturated carbocyclic ring having up to 6 carbon atoms and m denotes a number from I to 6, and A and B are identical or different and denote hydrogen lower alkyl or halogen, or a salt thereof, for the manufacture of a medicament for the treatment and prevention of glomerular nephritis, lung cancer, multiple sclerosis, ocular inflammation, osteoporosis, reperfusion. injury and tinnitus.
2. Use of a compound of the general formula (I) according to claim 1, wherein RI represents a group of the formula 2 -OR 2 or -N 3 R wherein R2 and R3 are identical or different and represent hydrogen, lower alkyl, benzyl, phenyl or a group of the formula R R 4 1 4 1 5 -CIH-CO R' -L;H-CH-OR 2 2 R 4 R 4 1 6 1 7 -CH-O-R or -CH R 0 Y 0 0 wherein R4 represents hydrogen, lower alkyl, phenyl or benzyl, which can optionally be substituted by hydroxyl, lower alkoxycarbonyl, carboxyl, lower alkylthio, heteroaryl or carbamoyl, R5 represents hydrogen, lower alkyl, phenyl or benzyl, R6 represents a group of the formula -COR5 or -C02R5, and R7 represents hydrogen, lower alkyl or phenyl, Y represents a group of the formula R I (-L; Mn wherein R8 represents hydrogen, lower alkyl or phenyl, and n denotes a number from 0 to 5, z represents norbornyl, or represents a group of the formula CH io C 10 R 11.1. R -C"-.rR 9 or -C "1 9 (C), (C), wherein R9 and RIO are identical or different and denote hydrogen, lower alkyl or phenyl, or R9 and RIO can together form a saturated carbocyclic ring having up to 6 carbon atoms and m denotes a number from I to 6, A and B are identical or different and denote hydrogen, methyl, ethyl, fluorine, chlorine or bromine for the manufacture of a medicament for the treatment and prevention of glomerular nephritis, lung cancer, multiple sclerosis, ocular inflammation, osteoporosis, reperfusion injury and tinnitus.
3. Use of a compound of general formula (1) according to claim 1, or a salt thereof, wherein RI represents a group of the formula -OR 2 or wherein R2 and 0 are identical or different and represent hydrogen, methyl, ethyl, propyl, isopropyl, butyl, tert.-butyl, phenyl or benzyl, or represent a group of the formula 5 R R 4 1 4 5 1 5 -C;H-CO R -UH-CH-OR 2 2 R 4 R 4 1 1 -CH-0-R 6 or -UI R 7 0 Y 0 0 wherein R4 represents hydrogen, methyl, ethyl, propyl, isopropyl, 10 butyl, tert.- butyl, benzyl or phenyl, which can optionally be substituted by hydroxyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, carboxyl, methylthio, ethylthio, propylthio, imidazolyl or carbamoyl, 15 R5 represents hydrogen, methyl, ethyl, propyl, isopropyl, butyl, tert.-butyl, phenyl or benzyl, R6 represents a group of the formula -COR5 or -C02R5' 20 and R7 represents hydrogen, methyl, ethyl, propyl, isopropyl, butyl, tert.-butyl or phenyl, Y represents a group of the formula R 8 1 wherein 5 R8 represents hydrogen, methyl, ethyl, propyl, isopropyl, butyl, tert.- butyl or phenyl, and n denotes a number from 0 to 5, z represents norbornyl or represents a group of the formula CH R jo C 10 9 or -C,--jj--R L4--R 9 (C), wherein R9 and RIO are identical or different and denote hydrogen, methyl, ethyl, n-propyl, iso-propyl, butyl or tert.-butyl, or 20 R9 and RIO can together form a saturated carbocyclic ring having up to 6 carbon atoms and m denotes a number form I to 6, and 25 A and B are identical or different and denote hydrogen, methyl, ethyl, fluorine or chlorine for the manufacture of a medicament for the treatment and prevention of glomerular nephritis, lung cancer, multiple sclerosis, ocular inflammation, osteoporosis, reperfusion injury and tinnitus.
4. Use of a compound of general formula (1) according to claim 1, or salts thereof, wherein R2 and R3 are identical or different and represent hydrogen or methyl, or represent a group of the formula R R 4 14 5 1 5 -CH-CO 2 R -CH-CHT-OR, R 4 R 4 1 1 1 6 or -L;t 7 -CH-0-R R 0 Y 0 0 wherein R4 represents hydrogen, methyl or phenyl, 15 R5 represents hydrogen, methyl, ethyl, tert.-butyl or benzyl, R6 represents a group of the formula -COR5, R7 represents methyl, R8 represents hydrogen or methyl, n denotes the number 0 or 1, R9 and RIO are identical or different and denote hydrogen or methyl, or R9 and RIO together form a cyclohexyl ring, and m denotes the number 1, 2, 33, 4 or 5, and A and B denote hydrogen or fluorine.
5. Use of a compound according to claim 1, wherein such compound is 2-[4 (quinolin-2-yl-methoxy)phenyl]-2-cyclopen4.ylacetic acid of the formula 0 rN'r C02 H or a salt thereof for the manufacture of a medicament for the treatment and prevention of glomerular nephritis, lung cancer, multiple sclerosis, ocular inflammation, osteoporosis, reperfusion injury and tinnitus.
6. A compound according to claim 5, wherein such compound is the (+)-enantiomer.
7. Use of a compound according to claim 5, wherein such compound is the (-)-enantiomer.

7. A compound according to claim 5, wherein such compound is the (-)-enantiomer.

2-G Amendments to the claims have been filed as follows 1. Use of a compound of the general formula (I) B A 0 Y-Z 0 R in which RI represents a group of the formula --OR 2 or -N R.

wherein R2 and R3 are identical or different and represent hydrogen, aIkyl, aryl, aralkyl or a group of the formula R4 R 4 1 5 1 - -CH-C02R -CH CHF-OR', R 4 R 4 1 6 1 7 -CH-O-R or -CH R 0 Y 0 0 wherein R4 represents hydrogen, alkyl, aralkyl or aryl, which can optionally be substituted by hydroxyl, carboxyl, alkoxycarbonyl, alkylthio, heteroaryl or carbamoyl, R5 represents hydrogen, alkyl, aryl or aralkyl, R6 represents a group of the formula -COR5 or -C02R5' R7 represents hydrogen, alkyl or aryl, Y represents a group of the formula R 8 1 wherein R8 represents hydrogen, alkyl or aryl and n denotes a number from 0 to 5, z represents norbomyl, or represents a group of the formula CH jo C 10 9 or 1-1t-R - C:1 -"r R -IR 9 (C)" (C)M wherein 25 R9 and RIO are identical or different and denote hydrogen, alkyl or aryl, or 2-% R9 and RIO can together form a saturated carbocyclic ring having up to 6 carbon atoms and m denotes a number from I to 6, and A and B are identical or different and denote hydrogen lower alkyl or halogen, C) or a salt thereof, for the manufacture of a medicament for the treatment and prevention of glomerular nephritis, lung cancer, multiple sclerosis, ocular inflammation, osteoporosis, reperfusion injury and tinnitus.

2. Use of a compound of the general formula (I) according to claim 1, wherein RI represents a group of the formula -OR 2 or - N R wherein R2 and R3 are identical or different and represent hydrogen, lower alkyl, benzyl, phenyl or a group of the formula 2C4 R 4 R 4 1 -CH-CO 2 R -UH-CHF-OR5, R 4 R 4 7 6 R -CH-0-R or 0 Y 0 0 wherein R4 represents hydrogen, lower alkyl, phenyl or benzyl, which can optionally be substituted by hydroxyl, lower alkoxycarbonyl, carboxyl, lower alkylthio, heteroaryl or carbamoyl, R5 represents hydrogen, lower alkyl, phenyl or benzyl, R6 represents a group of the formula -COR5 or -C02R5, and R7 represents hydrogen, lower alkyl or phenyl, Y represents a group of the formula R 8 wherein 20 R8 represents hydrogen, lower alkyl or phenyl, and n denotes a number from 0 to 5, z represents norbornyl, or represents a group of the formula ,-,CH R lo C 10 -R -C or -C 9 rR9 L4--R wherein R9 and R 10 are identical or different and denote hydrogen, lower alkyl or phenyl, or R9 and RIO can together form a saturated carbocyclic ring having up to 6 carbon atoms and m denotes a number from I to 6, A and B are identical or different and denote hydrogen, methyl, ethyl, fluorine, chlorine or bromine f6r the manufacture of a medicament for the treatment and prevention of glomerular nephritis, lung cancer, multiple sclerosis, ocular inflammation, osteoporosis, reperfusion injury and tinnitus.

3. Use of a compound of general formula (I) according to claim 1, or a salt thereof, wherein RI represents a group of the formula -OR 2 or I--, R 3 wherein R2 and 0 are identical or different and represent hydrogen, methyl, ethyl, propyl, isopropyl, butyl, tert.-butyl, phenyl or benzyl, or represent a group of the formula 5 R4 R 4 1 5 1 -CH-CO 2 R -UH-uIF-OR' R 4 R 4 1 7 6 _L;H R -CH-0-R or -I _ 0 Y 0 0 wherein R4 represents hydrogen, methyl, ethyl, propyl, isopropyl, 10 butyl, tert.- butyl, benzyl or phenyl, which can optionally be substituted by- hydroxyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, carboxyl, methylthio, ethylthio, propylthio, imidazolyl or carbamoyl, R5 represents hydrogen, methyl, ethyl, propyl, isopropyl, butyl, tert.-butyl, phenyl or benzyl, R6 represents a group of the formula -COR5 or -C02R5, and R7 represents hydrogen, methyl, ethyl, propyl, isopropyl, butyl, tert.-butyl or phenyl, CS 7- Y represents a group of the formula R 8 1 (-L I;tl)n wherein 5 R8 represents hydrogen, methyl, ethyl, propyl, isopropyl, butyl, tert.- butyl or phenyl, and n denotes a number from 0 to 5, z represents norbornyl or represents a group of the formula CH 10 C 10 _C::rR 9 or C R R I I R 9 (C)" (C)M wherein R9 and RIO are identical or different and denote hydrogen, methyl, ethyl, n-propyl, iso-propyl, butyl or tert.-butyl, or 20 R9 and RIO can together form a saturated carbocyclic ring having up to 6 carbon atoms and m denotes a number form I to 6, and 25 A and B are identical or different and denote hydrogen, methyl, ethyl, fluorine or chlorine for the manufacture of a medicament for the treatment and prevention of glomerular nephritis, lung cancer, multiple sclerosis, ocular inflammation, osteoporosis, reperfusion injury and tinnitus.

4. Use of a compound of general formula (I) according to claim 1, or salts thereof, wherein R2 and R3 are identical or different and represent hydrogen or methyl, or represent a group of the formula R 4 R 4 1 5 1 5 -CH-CO 2 R R 4 R 4 1 1 -CH-0-R 6 or -L;H R 7 0 0 Y 0 wherein R4 represents hydrogen, methyl or phenyl, 15 represents hydrogen, methyl, ethyl, tert.-butyl or benzyl, R6 represents a group of the formula -COR5, R7 represents methyl, R8 represents hydrogen or methyl, n denotes the number 0 or 1, 34- R9 and RIO are identical or different and denote hydrogen or methyl, or R9 and R 10 together form a cyclohexyl ring, and m denotes the number 1, 2, 3, 4 or 5, and A and B denote hydrogen or fluorine.

5. Use of a compound according to claim 1, wherein such compound is 2-[4 (quinolin-2-yl-methoxy)phenyl]-2-cyclopentylacetic acid of the formula 0 C C02 H or a salt thereof for the manufacture of a medicament for the treatment and prevention of glomerular nephritis, lung cancer, multiple sclerosis, ocular inflammation, osteoporosis, reperfusion injury and tinnitus.

6. Use of a compound according to claim 5, wherein such compound is the (+)-enantiomer.