GB2356138A - Use of substituted 4-(quinolin-2-yl-methoxy)phenyl-acetic acid derivatives for the treatment of diseases - Google Patents
Use of substituted 4-(quinolin-2-yl-methoxy)phenyl-acetic acid derivatives for the treatment of diseases Download PDFInfo
- Publication number
- GB2356138A GB2356138A GB9926983A GB9926983A GB2356138A GB 2356138 A GB2356138 A GB 2356138A GB 9926983 A GB9926983 A GB 9926983A GB 9926983 A GB9926983 A GB 9926983A GB 2356138 A GB2356138 A GB 2356138A
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- United Kingdom
- Prior art keywords
- formula
- group
- phenyl
- hydrogen
- methyl
- Prior art date
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- MYPFKEGUMKPGDR-UHFFFAOYSA-N 2-[4-(quinolin-2-ylmethoxy)phenyl]acetic acid Chemical class C1=CC(CC(=O)O)=CC=C1OCC1=CC=C(C=CC=C2)C2=N1 MYPFKEGUMKPGDR-UHFFFAOYSA-N 0.000 title abstract description 6
- 201000010099 disease Diseases 0.000 title description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 2
- 239000001257 hydrogen Substances 0.000 claims abstract description 83
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 83
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 68
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 44
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 206010061218 Inflammation Diseases 0.000 claims abstract description 12
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 12
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 12
- 208000009205 Tinnitus Diseases 0.000 claims abstract description 12
- 230000004054 inflammatory process Effects 0.000 claims abstract description 12
- 201000005202 lung cancer Diseases 0.000 claims abstract description 12
- 208000020816 lung neoplasm Diseases 0.000 claims abstract description 12
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 12
- 231100000886 tinnitus Toxicity 0.000 claims abstract description 12
- 206010018364 Glomerulonephritis Diseases 0.000 claims abstract description 11
- 206010063837 Reperfusion injury Diseases 0.000 claims abstract description 11
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
- 150000001875 compounds Chemical class 0.000 claims description 37
- -1 tert.- butyl Chemical group 0.000 claims description 31
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 21
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 20
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 19
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 16
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 239000011737 fluorine Substances 0.000 claims description 12
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- 125000002837 carbocyclic group Chemical group 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 230000002265 prevention Effects 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- ZEYYDOLCHFETHQ-JOCHJYFZSA-N (2r)-2-cyclopentyl-2-[4-(quinolin-2-ylmethoxy)phenyl]acetic acid Chemical compound C1([C@@H](C(=O)O)C=2C=CC(OCC=3N=C4C=CC=CC4=CC=3)=CC=2)CCCC1 ZEYYDOLCHFETHQ-JOCHJYFZSA-N 0.000 claims description 4
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
- 125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims 8
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 208000027418 Wounds and injury Diseases 0.000 claims 1
- 230000006378 damage Effects 0.000 claims 1
- 208000014674 injury Diseases 0.000 claims 1
- 230000010410 reperfusion Effects 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 4
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000003820 Lipoxygenases Human genes 0.000 description 3
- 108090000128 Lipoxygenases Proteins 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
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- 230000005764 inhibitory process Effects 0.000 description 3
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 150000005840 aryl radicals Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- STFVRLSMTLIUIG-UHFFFAOYSA-N 2-[3-[2-(quinolin-2-ylmethoxy)phenyl]cyclopentyl]acetic acid Chemical compound C1C(CC(=O)O)CCC1C1=CC=CC=C1OCC1=CC=C(C=CC=C2)C2=N1 STFVRLSMTLIUIG-UHFFFAOYSA-N 0.000 description 1
- 125000003229 2-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- XEXBWIHRLSBNFX-UHFFFAOYSA-N 3-cyclohexyl-2-[4-(quinolin-2-ylmethoxy)phenyl]propanoic acid Chemical compound C=1C=C(OCC=2N=C3C=CC=CC3=CC=2)C=CC=1C(C(=O)O)CC1CCCCC1 XEXBWIHRLSBNFX-UHFFFAOYSA-N 0.000 description 1
- OAYHRVHPUKGQQV-UHFFFAOYSA-N 3-cyclopropyl-2-[4-(quinolin-2-ylmethoxy)phenyl]propanoic acid Chemical compound C=1C=C(OCC=2N=C3C=CC=CC3=CC=2)C=CC=1C(C(=O)O)CC1CC1 OAYHRVHPUKGQQV-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 description 1
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
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- 235000011054 acetic acid Nutrition 0.000 description 1
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- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 239000008159 sesame oil Substances 0.000 description 1
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- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000008275 solid aerosol Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
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- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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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 (7)
- Patent claimsI 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.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9926983A GB2356138A (en) | 1999-11-15 | 1999-11-15 | Use of substituted 4-(quinolin-2-yl-methoxy)phenyl-acetic acid derivatives for the treatment of diseases |
| PCT/EP2000/010922 WO2001035960A1 (en) | 1999-11-15 | 2000-11-06 | Use of substituted 4-(quinolin 2-yl-methoxy)phenyl-acetic acid derivatives for the treatment of diseases |
| AU15189/01A AU1518901A (en) | 1999-11-15 | 2000-11-06 | Use of substituted 4-(quinolin 2-yl-methoxy)phenyl-acetic acid derivatives for the treatment of diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9926983A GB2356138A (en) | 1999-11-15 | 1999-11-15 | Use of substituted 4-(quinolin-2-yl-methoxy)phenyl-acetic acid derivatives for the treatment of diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB9926983D0 GB9926983D0 (en) | 2000-01-12 |
| GB2356138A true GB2356138A (en) | 2001-05-16 |
Family
ID=10864540
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB9926983A Withdrawn GB2356138A (en) | 1999-11-15 | 1999-11-15 | Use of substituted 4-(quinolin-2-yl-methoxy)phenyl-acetic acid derivatives for the treatment of diseases |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU1518901A (en) |
| GB (1) | GB2356138A (en) |
| WO (1) | WO2001035960A1 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0344519A1 (en) * | 1988-05-31 | 1989-12-06 | Bayer Ag | Substituted 4-(quinolin-2-yl-methoxy)phenyl-acetic-acid derivatives |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4112533A1 (en) * | 1991-04-17 | 1992-10-22 | Bayer Ag | METHOD FOR THE PRODUCTION OF ENANTIOMER-PURE SUBSTITUTED (CHINOLIN-2-YL-METHOXY) PHENYL ACETIC ACIDS |
-
1999
- 1999-11-15 GB GB9926983A patent/GB2356138A/en not_active Withdrawn
-
2000
- 2000-11-06 WO PCT/EP2000/010922 patent/WO2001035960A1/en not_active Ceased
- 2000-11-06 AU AU15189/01A patent/AU1518901A/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0344519A1 (en) * | 1988-05-31 | 1989-12-06 | Bayer Ag | Substituted 4-(quinolin-2-yl-methoxy)phenyl-acetic-acid derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2001035960A1 (en) | 2001-05-25 |
| AU1518901A (en) | 2001-05-30 |
| GB9926983D0 (en) | 2000-01-12 |
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| Date | Code | Title | Description |
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| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |