HRP980046A2 - 5-aroylnaphthalene derivatives - Google Patents
5-aroylnaphthalene derivativesInfo
- Publication number
- HRP980046A2 HRP980046A2 HR60/036,466A HRP980046A HRP980046A2 HR P980046 A2 HRP980046 A2 HR P980046A2 HR P980046 A HRP980046 A HR P980046A HR P980046 A2 HRP980046 A2 HR P980046A2
- Authority
- HR
- Croatia
- Prior art keywords
- hydrogen
- compound according
- alkyl
- cyano
- group
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims description 154
- -1 nitro, hydroxy Chemical group 0.000 claims description 88
- 239000001257 hydrogen Substances 0.000 claims description 68
- 229910052739 hydrogen Inorganic materials 0.000 claims description 68
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 150000002431 hydrogen Chemical class 0.000 claims description 53
- 238000000034 method Methods 0.000 claims description 48
- 239000000203 mixture Substances 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 25
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 125000002252 acyl group Chemical group 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
- 125000001188 haloalkyl group Chemical group 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- GJFYSLWEOSGLHZ-UHFFFAOYSA-N 5-(4-fluorobenzoyl)-6-methoxynaphthalene-2-sulfonamide Chemical compound COC1=CC=C2C=C(S(N)(=O)=O)C=CC2=C1C(=O)C1=CC=C(F)C=C1 GJFYSLWEOSGLHZ-UHFFFAOYSA-N 0.000 claims description 7
- 208000023275 Autoimmune disease Diseases 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 125000005366 cycloalkylthio group Chemical group 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 229940002612 prodrug Drugs 0.000 claims description 7
- 239000000651 prodrug Substances 0.000 claims description 7
- UPKXQEHNLYCAFF-UHFFFAOYSA-N 1-(4-fluorobenzoyl)-6-methylsulfonylnaphthalene-2-carbonitrile Chemical compound N#CC=1C=CC2=CC(S(=O)(=O)C)=CC=C2C=1C(=O)C1=CC=C(F)C=C1 UPKXQEHNLYCAFF-UHFFFAOYSA-N 0.000 claims description 6
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 229910020008 S(O) Inorganic materials 0.000 claims description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 5
- 125000004476 heterocycloamino group Chemical group 0.000 claims description 5
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- ZMQKCCDRPOSEOH-UHFFFAOYSA-N 1-benzoyl-6-methylsulfonylnaphthalene-2-carbonitrile Chemical compound N#CC=1C=CC2=CC(S(=O)(=O)C)=CC=C2C=1C(=O)C1=CC=CC=C1 ZMQKCCDRPOSEOH-UHFFFAOYSA-N 0.000 claims description 4
- UEYICAYNQHDAPU-UHFFFAOYSA-N 5-(3-fluorobenzoyl)-6-methoxynaphthalene-2-sulfonamide Chemical compound COC1=CC=C2C=C(S(N)(=O)=O)C=CC2=C1C(=O)C1=CC=CC(F)=C1 UEYICAYNQHDAPU-UHFFFAOYSA-N 0.000 claims description 4
- WQJHZIJUPIDPOH-UHFFFAOYSA-N 6-cyano-5-(4-fluorobenzoyl)naphthalene-2-sulfonamide Chemical compound N#CC=1C=CC2=CC(S(=O)(=O)N)=CC=C2C=1C(=O)C1=CC=C(F)C=C1 WQJHZIJUPIDPOH-UHFFFAOYSA-N 0.000 claims description 4
- JVYMKTAPCLSXLC-UHFFFAOYSA-N COClO Chemical compound COClO JVYMKTAPCLSXLC-UHFFFAOYSA-N 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 4
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 4
- 230000002757 inflammatory effect Effects 0.000 claims description 4
- 231100000252 nontoxic Toxicity 0.000 claims description 4
- 230000003000 nontoxic effect Effects 0.000 claims description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
- 230000010933 acylation Effects 0.000 claims description 3
- 238000005917 acylation reaction Methods 0.000 claims description 3
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 3
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 2
- 206010006811 Bursitis Diseases 0.000 claims description 2
- 201000005569 Gout Diseases 0.000 claims description 2
- 201000002481 Myositis Diseases 0.000 claims description 2
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 2
- 206010003246 arthritis Diseases 0.000 claims description 2
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
- XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 claims description 2
- KIWSYRHAAPLJFJ-DNZSEPECSA-N n-[(e,2z)-4-ethyl-2-hydroxyimino-5-nitrohex-3-enyl]pyridine-3-carboxamide Chemical compound [O-][N+](=O)C(C)C(/CC)=C/C(=N/O)/CNC(=O)C1=CC=CN=C1 KIWSYRHAAPLJFJ-DNZSEPECSA-N 0.000 claims description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 201000004595 synovitis Diseases 0.000 claims description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 4
- XBRICTIWURKBNP-UHFFFAOYSA-N OCCOClO Chemical group OCCOClO XBRICTIWURKBNP-UHFFFAOYSA-N 0.000 claims 1
- 239000000543 intermediate Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 44
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
- 230000015572 biosynthetic process Effects 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 238000003786 synthesis reaction Methods 0.000 description 20
- 241000700159 Rattus Species 0.000 description 18
- 125000004432 carbon atom Chemical group C* 0.000 description 16
- 239000004215 Carbon black (E152) Substances 0.000 description 15
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 229930195733 hydrocarbon Natural products 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- 229910052938 sodium sulfate Inorganic materials 0.000 description 15
- 235000011152 sodium sulphate Nutrition 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 230000003110 anti-inflammatory effect Effects 0.000 description 13
- 238000004587 chromatography analysis Methods 0.000 description 13
- 239000012266 salt solution Substances 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- 150000003254 radicals Chemical class 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- 125000004429 atom Chemical group 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 150000003180 prostaglandins Chemical class 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 8
- 239000004615 ingredient Substances 0.000 description 8
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 210000004712 air sac Anatomy 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 238000010828 elution Methods 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- QPHXXRHCBGDDJS-UHFFFAOYSA-N (4-fluorophenyl)-(2-hydroxy-6-methylsulfonylnaphthalen-1-yl)methanone Chemical compound OC=1C=CC2=CC(S(=O)(=O)C)=CC=C2C=1C(=O)C1=CC=C(F)C=C1 QPHXXRHCBGDDJS-UHFFFAOYSA-N 0.000 description 6
- CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 230000000202 analgesic effect Effects 0.000 description 6
- 239000000679 carrageenan Substances 0.000 description 6
- 235000010418 carrageenan Nutrition 0.000 description 6
- 229920001525 carrageenan Polymers 0.000 description 6
- 229940113118 carrageenan Drugs 0.000 description 6
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 6
- 229960002986 dinoprostone Drugs 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000000463 material Substances 0.000 description 6
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- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 6
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 6
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- 125000002947 alkylene group Chemical group 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
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- 125000001072 heteroaryl group Chemical group 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- OCUGBFPTNSQSDJ-UHFFFAOYSA-N (2-methoxy-6-methylsulfonylnaphthalen-1-yl)-phenylmethanone Chemical compound COC1=CC=C2C=C(S(C)(=O)=O)C=CC2=C1C(=O)C1=CC=CC=C1 OCUGBFPTNSQSDJ-UHFFFAOYSA-N 0.000 description 4
- WTSMEQARCCMWGM-UHFFFAOYSA-N (4-fluorophenyl)-(2-methoxy-6-methylsulfonylnaphthalen-1-yl)methanone Chemical compound COC1=CC=C2C=C(S(C)(=O)=O)C=CC2=C1C(=O)C1=CC=C(F)C=C1 WTSMEQARCCMWGM-UHFFFAOYSA-N 0.000 description 4
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 4
- YVKCZGIZEJHWCR-UHFFFAOYSA-N 5-(2-fluorobenzoyl)-6-methoxynaphthalene-2-sulfonamide Chemical compound COC1=CC=C2C=C(S(N)(=O)=O)C=CC2=C1C(=O)C1=CC=CC=C1F YVKCZGIZEJHWCR-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
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- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
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- 125000006413 ring segment Chemical group 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
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- 125000003396 thiol group Chemical group [H]S* 0.000 description 4
- BNOMSHBIVYJTHY-UHFFFAOYSA-N (2-hydroxy-6-methylsulfonylnaphthalen-1-yl)-phenylmethanone Chemical compound OC=1C=CC2=CC(S(=O)(=O)C)=CC=C2C=1C(=O)C1=CC=CC=C1 BNOMSHBIVYJTHY-UHFFFAOYSA-N 0.000 description 3
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 3
- JNYZIGMFVCYMMB-UHFFFAOYSA-N 1-(4-chlorobenzoyl)-6-methylsulfonylnaphthalene-2-carbonitrile Chemical compound N#CC=1C=CC2=CC(S(=O)(=O)C)=CC=C2C=1C(=O)C1=CC=C(Cl)C=C1 JNYZIGMFVCYMMB-UHFFFAOYSA-N 0.000 description 3
- LRDYFLSPMAZWPE-UHFFFAOYSA-N 1-(4-fluorophenyl)sulfonyl-2-methoxy-6-methylsulfonylnaphthalene Chemical compound COC1=CC=C2C=C(S(C)(=O)=O)C=CC2=C1S(=O)(=O)C1=CC=C(F)C=C1 LRDYFLSPMAZWPE-UHFFFAOYSA-N 0.000 description 3
- DLKQHBOKULLWDQ-UHFFFAOYSA-N 1-bromonaphthalene Chemical compound C1=CC=C2C(Br)=CC=CC2=C1 DLKQHBOKULLWDQ-UHFFFAOYSA-N 0.000 description 3
- WPJQZSOSBHCSBT-UHFFFAOYSA-N 2-methoxy-6-methylsulfonylnaphthalene Chemical compound C1=C(S(C)(=O)=O)C=CC2=CC(OC)=CC=C21 WPJQZSOSBHCSBT-UHFFFAOYSA-N 0.000 description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- UWPJYQYRSWYIGZ-UHFFFAOYSA-N 5-aminonaphthalene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=C2C(N)=CC=CC2=C1 UWPJYQYRSWYIGZ-UHFFFAOYSA-N 0.000 description 3
- MHNZIWBNSRLGPL-UHFFFAOYSA-N 6-methoxy-5-(4-methylbenzoyl)naphthalene-2-sulfonamide Chemical compound COC1=CC=C2C=C(S(N)(=O)=O)C=CC2=C1C(=O)C1=CC=C(C)C=C1 MHNZIWBNSRLGPL-UHFFFAOYSA-N 0.000 description 3
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- 208000024827 Alzheimer disease Diseases 0.000 description 3
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 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 3
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Classifications
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
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- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/40—Radicals substituted by oxygen atoms
- C07D307/46—Doubly bound oxygen atoms, or two oxygen atoms singly bound to the same carbon atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Diabetes (AREA)
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- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Luminescent Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US3646697P | 1997-01-28 | 1997-01-28 |
Publications (1)
Publication Number | Publication Date |
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HRP980046A2 true HRP980046A2 (en) | 1998-10-31 |
Family
ID=21888759
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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HR60/036,466A HRP980046A2 (en) | 1997-01-28 | 1998-01-28 | 5-aroylnaphthalene derivatives |
Country Status (38)
Country | Link |
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US (2) | US5962531A (it) |
EP (1) | EP0966437B1 (it) |
JP (1) | JP3607706B2 (it) |
KR (1) | KR100313180B1 (it) |
CN (1) | CN1159293C (it) |
AR (1) | AR011571A1 (it) |
AT (1) | ATE219051T1 (it) |
AU (1) | AU721407B2 (it) |
BR (1) | BR9807520A (it) |
CA (1) | CA2278687C (it) |
CO (1) | CO4930273A1 (it) |
CZ (1) | CZ259399A3 (it) |
DE (2) | DE69805974T2 (it) |
DK (1) | DK0966437T3 (it) |
ES (2) | ES2178162T3 (it) |
FR (1) | FR2758818B1 (it) |
GB (1) | GB2321457B (it) |
HR (1) | HRP980046A2 (it) |
HU (1) | HUP0001061A3 (it) |
ID (1) | ID22825A (it) |
IL (1) | IL130909A0 (it) |
IT (1) | IT1298159B1 (it) |
MA (1) | MA26469A1 (it) |
NO (1) | NO313136B1 (it) |
NZ (1) | NZ336684A (it) |
PA (1) | PA8444901A1 (it) |
PE (1) | PE51499A1 (it) |
PL (1) | PL334769A1 (it) |
PT (1) | PT966437E (it) |
RU (1) | RU2188192C2 (it) |
SV (1) | SV1998000013A (it) |
TN (1) | TNSN98013A1 (it) |
TR (1) | TR199901783T2 (it) |
TW (1) | TW520355B (it) |
UY (1) | UY24860A1 (it) |
WO (1) | WO1998032732A1 (it) |
YU (1) | YU34499A (it) |
ZA (1) | ZA98495B (it) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
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CA2418832A1 (en) * | 2000-08-09 | 2002-02-14 | F. Hoffmann-La Roche Ag | Quinolene derivatives as anti-inflammation agents |
JP2005518444A (ja) * | 2002-02-22 | 2005-06-23 | ファルマシア アンド アップジョン カンパニー リミティド ライアビリティー カンパニー | アリールスルホン誘導体 |
WO2003104178A1 (en) * | 2002-06-07 | 2003-12-18 | Cortical Pty Ltd | Napththalene derivatives which inhibit the cytokine or biological activity of macrophage migration inhibitory factor (mif) |
CA2524568C (en) * | 2003-03-31 | 2012-07-17 | Council Of Scientific & Industrial Research | Mercapto-phenyl-naphthyl-methane derivatives and preparation thereof |
EP1534305B9 (en) | 2003-05-07 | 2007-03-07 | Osteologix A/S | Treating cartilage / bone conditions with water-soluble strontium salts |
JP2009541219A (ja) * | 2006-06-12 | 2009-11-26 | メルク エンド カムパニー インコーポレーテッド | 高眼圧治療のための眼科組成物 |
EP2788332A1 (en) | 2011-12-07 | 2014-10-15 | Amgen, Inc. | Bicyclic aryl and heteroaryl sodium channel inhibitors |
WO2014201173A1 (en) | 2013-06-12 | 2014-12-18 | Amgen Inc. | Bicyclic sulfonamide compounds as sodium channel inhibitors |
Family Cites Families (24)
Publication number | Priority date | Publication date | Assignee | Title |
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CH384567A (de) * | 1958-10-17 | 1964-11-30 | Geigy Ag J R | Verfahren zur Herstellung neuer Benzophenonsulfonamide |
NL6816241A (it) * | 1967-12-01 | 1969-06-03 | ||
US3655679A (en) * | 1969-06-25 | 1972-04-11 | Merck & Co Inc | Certain aryl pyridine carboxylic acid derivatives |
US3755455A (en) * | 1970-12-09 | 1973-08-28 | Sandoz Ag | (1-alkoxy-2-naphthyl)-substituted or unsubstituted phenylketones |
US3899529A (en) * | 1973-02-22 | 1975-08-12 | Merck & Co Inc | Aroyl substituted naphthalene acetic acids |
GB1468111A (en) * | 1976-01-08 | 1977-03-23 | Pfizer Ltd | Thiophene-sulphonamides |
US4226783A (en) * | 1978-07-03 | 1980-10-07 | E. I. Du Pont De Nemours And Company | α-Chlorination process |
US4406896A (en) * | 1979-12-20 | 1983-09-27 | Merck & Co., Inc. | Adjuvants for rectal delivery of drug substances |
NZ196349A (en) * | 1980-03-07 | 1984-08-24 | Interx Research Corp | Enhancement of absorption rate of orally administered polar bioactive agents |
NZ196348A (en) * | 1980-03-07 | 1984-08-24 | Interx Research Corp | Enhancement of absorption rate of orally administered antibiotics |
CA1248536A (en) * | 1982-09-10 | 1989-01-10 | Wellcome Foundation Limited (The) | Benzoil acid derivatives |
FR2617476B1 (fr) * | 1987-07-03 | 1989-11-17 | Oreal | Nouveaux derives polycycliques aromatiques, leur procede de preparation et leur utilisation en medecine humaine et veterinaire et en cosmetique |
DE3823318A1 (de) * | 1988-07-09 | 1990-02-22 | Bayer Ag | (hetero)aryloxynaphthaline mit ueber schwefel gebundenen substituenten |
DK77393D0 (da) * | 1993-06-29 | 1993-06-29 | Novo Nordisk As | Aktivering af enzymer |
WO1995004530A1 (en) * | 1993-08-06 | 1995-02-16 | Smithkline Beecham Corporation | Endothelin receptor antagonists |
US5491140A (en) * | 1994-06-30 | 1996-02-13 | Eli Lilly And Company | Naphthyl tachykinin receptor antagonists to treat physiological conditions |
US5538991A (en) * | 1994-09-14 | 1996-07-23 | Merck & Co., Inc. | Endothelin antagonists bearing 5-membered heterocyclic amides |
US7501441B1 (en) * | 1994-09-20 | 2009-03-10 | Eli Lilly And Company | Naphthyl compounds, intermediates, processes, compositions, and methods |
WO1996018616A1 (en) * | 1994-12-12 | 1996-06-20 | Merck & Co., Inc. | Substituted 2-aminopyridines as inhibitors of nitric oxide synthase |
AU4515896A (en) * | 1994-12-12 | 1996-07-03 | Merck & Co., Inc. | Substituted 2-acylamino-pyridines as inhibitors of nitric oxide synthase |
DE59603311D1 (de) * | 1995-01-30 | 1999-11-18 | Hoechst Ag | Basisch-substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
US5998401A (en) * | 1995-02-28 | 1999-12-07 | Eli Lilly And Company | Naphthyl compounds, intermediates, compositions, and methods |
US6391892B1 (en) * | 1995-03-10 | 2002-05-21 | Eli Lilly And Company | Naphthyl pharmaceutical compounds |
US6451817B1 (en) * | 1995-03-10 | 2002-09-17 | Eli Lilly And Company | Alpha-substituted-1-benzyl-napthyls |
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1998
- 1998-01-20 PA PA19988444901A patent/PA8444901A1/es unknown
- 1998-01-20 IT IT98MI000090A patent/IT1298159B1/it active IP Right Grant
- 1998-01-21 PL PL98334769A patent/PL334769A1/xx unknown
- 1998-01-21 ES ES98905325T patent/ES2178162T3/es not_active Expired - Lifetime
- 1998-01-21 IL IL13090998A patent/IL130909A0/xx unknown
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- 1998-01-21 BR BR9807520A patent/BR9807520A/pt not_active IP Right Cessation
- 1998-01-21 TR TR1999/01783T patent/TR199901783T2/xx unknown
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- 1998-01-21 AU AU60956/98A patent/AU721407B2/en not_active Ceased
- 1998-01-21 WO PCT/EP1998/000306 patent/WO1998032732A1/en not_active Application Discontinuation
- 1998-01-21 AT AT98905325T patent/ATE219051T1/de not_active IP Right Cessation
- 1998-01-21 EP EP98905325A patent/EP0966437B1/en not_active Expired - Lifetime
- 1998-01-21 RU RU99118507/04A patent/RU2188192C2/ru active
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- 1998-01-23 PE PE1998000049A patent/PE51499A1/es not_active Application Discontinuation
- 1998-01-26 AR ARP980100325A patent/AR011571A1/es unknown
- 1998-01-26 TN TNTNSN98013A patent/TNSN98013A1/fr unknown
- 1998-01-26 FR FR9800779A patent/FR2758818B1/fr not_active Expired - Fee Related
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- 1998-01-26 TW TW087101125A patent/TW520355B/zh active
- 1998-01-26 US US09/013,328 patent/US5962531A/en not_active Expired - Fee Related
- 1998-01-27 UY UY24860A patent/UY24860A1/es unknown
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- 1998-01-27 GB GB9801711A patent/GB2321457B/en not_active Expired - Fee Related
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- 1998-01-28 HR HR60/036,466A patent/HRP980046A2/hr not_active Application Discontinuation
- 1998-01-28 MA MA24949A patent/MA26469A1/fr unknown
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1999
- 1999-06-21 US US09/337,695 patent/US6150397A/en not_active Expired - Fee Related
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