SK736787A3 - Tolunitriles substituted by a heterocyclic residue and process for producing the same - Google Patents
Tolunitriles substituted by a heterocyclic residue and process for producing the same Download PDFInfo
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- SK736787A3 SK736787A3 SK7367-87A SK736787A SK736787A3 SK 736787 A3 SK736787 A3 SK 736787A3 SK 736787 A SK736787 A SK 736787A SK 736787 A3 SK736787 A3 SK 736787A3
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- 238000000034 method Methods 0.000 title claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 105
- 150000003839 salts Chemical class 0.000 claims description 46
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 44
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 23
- 230000003287 optical effect Effects 0.000 claims description 23
- -1 1-imidazolyl group Chemical group 0.000 claims description 22
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000000524 functional group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 2
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- 239000003886 aromatase inhibitor Substances 0.000 abstract description 5
- 230000000144 pharmacologic effect Effects 0.000 abstract description 5
- 229940046844 aromatase inhibitors Drugs 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 46
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 23
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 239000002253 acid Substances 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- 229940011871 estrogen Drugs 0.000 description 12
- 239000000262 estrogen Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- ICGOVDHTTBNXJI-UHFFFAOYSA-N 4-(1h-imidazol-2-ylmethyl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1CC1=NC=CN1 ICGOVDHTTBNXJI-UHFFFAOYSA-N 0.000 description 7
- 102000014654 Aromatase Human genes 0.000 description 7
- 108010078554 Aromatase Proteins 0.000 description 7
- 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 7
- 241000124008 Mammalia Species 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical class FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 230000002401 inhibitory effect Effects 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
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 5
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- 230000000694 effects Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000000155 melt Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 125000006505 p-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C#N)C([H])([H])* 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- MYXHSVDJKHADST-UHFFFAOYSA-N 4-(1-imidazol-1-ylethyl)benzonitrile Chemical compound C1=CN=CN1C(C)C1=CC=C(C#N)C=C1 MYXHSVDJKHADST-UHFFFAOYSA-N 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 description 3
- 229960005471 androstenedione Drugs 0.000 description 3
- AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 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
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 210000005075 mammary gland Anatomy 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
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- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
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- 229960001367 tartaric acid Drugs 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- KEEIWFHXOMZEJL-UHFFFAOYSA-N 4-(1h-1,2,4-triazol-5-ylmethyl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1CC1=NC=NN1 KEEIWFHXOMZEJL-UHFFFAOYSA-N 0.000 description 2
- RZNIQRKVBRNHBG-UHFFFAOYSA-N 4-(5-chloro-1-imidazol-1-ylpentyl)benzonitrile Chemical compound C1=CN=CN1C(CCCCCl)C1=CC=C(C#N)C=C1 RZNIQRKVBRNHBG-UHFFFAOYSA-N 0.000 description 2
- QGDXCRJMSYCFLO-UHFFFAOYSA-N 4-[1-imidazol-1-yl-2,2-bis(4-methoxyphenyl)ethenyl]benzonitrile Chemical group C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)=C(N1C=NC=C1)C1=CC=C(C#N)C=C1 QGDXCRJMSYCFLO-UHFFFAOYSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 229940122815 Aromatase inhibitor Drugs 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-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
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- 229920000881 Modified starch Polymers 0.000 description 2
- 239000004368 Modified starch Substances 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 206010046782 Uterine enlargement Diseases 0.000 description 2
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- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
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- 238000005899 aromatization reaction Methods 0.000 description 2
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- XDFORSMZCYHNBG-UHFFFAOYSA-N benzonitrile;hydrochloride Chemical compound Cl.N#CC1=CC=CC=C1 XDFORSMZCYHNBG-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical group C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 2
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000004802 cyanophenyl group Chemical group 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
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- 229910003002 lithium salt Inorganic materials 0.000 description 2
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- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 1
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- YSKDOVRYOHAINQ-UHFFFAOYSA-N 4-[1-(1H-imidazol-2-yl)-2-methylpropyl]benzonitrile Chemical compound C(C)(C)C(C=1NC=CN1)C1=CC=C(C#N)C=C1 YSKDOVRYOHAINQ-UHFFFAOYSA-N 0.000 description 1
- UGXZLJADRIDFRR-UHFFFAOYSA-N 4-[1-(1h-imidazol-2-yl)pentyl]benzonitrile;oxalic acid Chemical compound OC(=O)C(O)=O.C=1C=C(C#N)C=CC=1C(CCCC)C1=NC=CN1 UGXZLJADRIDFRR-UHFFFAOYSA-N 0.000 description 1
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- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- 125000005274 4-hydroxybenzoic acid group Chemical group 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/57—Nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Fats And Perfumes (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Saccharide Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
- Pyrrole Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Indole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/837,489 US4749713A (en) | 1986-03-07 | 1986-03-07 | Alpha-heterocycle substituted tolunitriles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK279102B6 SK279102B6 (sk) | 1998-06-03 |
| SK736787A3 true SK736787A3 (en) | 1998-06-03 |
Family
ID=25274596
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK7368-87A SK279103B6 (sk) | 1986-03-07 | 1987-03-06 | Substituované imidazolyl- alebo 1,2,4-triazolylmet |
| SK7367-87A SK736787A3 (en) | 1986-03-07 | 1987-03-06 | Tolunitriles substituted by a heterocyclic residue and process for producing the same |
| SK1512-87A SK151287A3 (en) | 1986-03-07 | 1987-03-06 | Process for producing tolunitriles substituted by a heterocyclic residue |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK7368-87A SK279103B6 (sk) | 1986-03-07 | 1987-03-06 | Substituované imidazolyl- alebo 1,2,4-triazolylmet |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1512-87A SK151287A3 (en) | 1986-03-07 | 1987-03-06 | Process for producing tolunitriles substituted by a heterocyclic residue |
Country Status (36)
| Country | Link |
|---|---|
| US (1) | US4749713A (es) |
| EP (1) | EP0236940B3 (es) |
| JP (1) | JPH0755930B2 (es) |
| KR (1) | KR910000482B1 (es) |
| AT (1) | ATE94873T1 (es) |
| BG (4) | BG45700A3 (es) |
| CA (1) | CA1316928C (es) |
| CY (1) | CY1905A (es) |
| CZ (3) | CZ279028B6 (es) |
| DD (1) | DD264432A5 (es) |
| DE (2) | DE3787480T2 (es) |
| DK (1) | DK172190B1 (es) |
| DZ (1) | DZ1055A1 (es) |
| ES (1) | ES2059317T3 (es) |
| FI (1) | FI91857C (es) |
| HK (1) | HK50296A (es) |
| HU (1) | HU202843B (es) |
| IE (1) | IE61101B1 (es) |
| IL (1) | IL81746A (es) |
| LU (1) | LU90128I2 (es) |
| LV (1) | LV5769B4 (es) |
| MA (1) | MA20888A1 (es) |
| MC (1) | MC1805A1 (es) |
| MT (1) | MTP998B (es) |
| MX (1) | MX5496A (es) |
| MY (1) | MY102428A (es) |
| NL (1) | NL970011I2 (es) |
| NO (2) | NO170277C (es) |
| PH (1) | PH24159A (es) |
| PL (2) | PL152025B1 (es) |
| PT (1) | PT84410B (es) |
| RO (2) | RO101532B1 (es) |
| SK (3) | SK279103B6 (es) |
| SU (3) | SU1470184A3 (es) |
| TN (1) | TNSN87033A1 (es) |
| ZA (1) | ZA871637B (es) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5112845A (en) * | 1986-03-07 | 1992-05-12 | Ciba-Geigy Corporation | Alpha-heterocycle substituted tolunitriles |
| US5352795A (en) * | 1986-03-07 | 1994-10-04 | Ciba-Geigy Corporation | Alpha-heterocycle substituted tolunitriles |
| GB8714013D0 (en) * | 1987-06-16 | 1987-07-22 | Ici Plc | (substituted-aralkyl)heterocyclic compounds |
| DE3811574A1 (de) * | 1988-03-31 | 1989-10-19 | Schering Ag | N-substituierte imidazole, verfahren zu ihrer herstellung sowie ihre verwendung in arzneimitteln |
| DE59010171D1 (de) * | 1989-07-14 | 1996-04-11 | Ciba Geigy Ag | Substituierte Benzonitrile |
| DE3926365A1 (de) * | 1989-08-04 | 1991-02-07 | Schering Ag | Cycloalkylenazole, verfahren zu deren herstellung, pharmazeutische praeparate, die diese enthalten sowie ihre verwendung zur herstellung von arzneimitteln |
| JP2602456B2 (ja) * | 1990-04-12 | 1997-04-23 | 雪印乳業株式会社 | 子宮内膜症治療剤 |
| EP0457716A1 (de) * | 1990-04-20 | 1991-11-21 | Ciba-Geigy Ag | Naphthalinderivate |
| DE4039559A1 (de) * | 1990-12-07 | 1992-06-11 | Schering Ag | Funktionalisierte vinylazole, verfahren zu deren herstellung, pharmazeutische praeparate die diese vinylazole enthalten sowie deren verwendung zur herstellung von arzneimitteln |
| TW210334B (es) * | 1990-12-12 | 1993-08-01 | Ciba Geigy Ag | |
| CH683151A5 (de) * | 1991-04-24 | 1994-01-31 | Ciba Geigy Ag | Antikonzeption bei weiblichen Primaten ohne Beeinflussung des menstruellen Zyklus. |
| DE4120107A1 (de) * | 1991-06-14 | 1992-12-17 | Schering Ag | Bicyclisch substituierte vinylimidazole, -triazole und -tetrazole |
| HU220863B1 (en) | 1991-09-02 | 2002-06-29 | Yamanouchi Pharma Co Ltd | Triazolylated tertiary amines, process for producing them and pharmaceutical compositions containing them |
| US5223539A (en) * | 1991-11-22 | 1993-06-29 | G. D. Searle & Co. | N,n-di-alkyl(phenoxy)benzamide derivatives |
| AU5285593A (en) * | 1992-10-21 | 1994-05-09 | Sankyo Company Limited | Azole compound |
| GB2273704B (en) * | 1992-12-16 | 1997-01-22 | Orion Yhtymae Oy | Triazolyl diaryl selective aromatase inhibiting compounds |
| US5426196A (en) * | 1993-12-22 | 1995-06-20 | Glaxo Inc. | Synthesis of diaryl methanes |
| JP2000505797A (ja) * | 1996-01-30 | 2000-05-16 | メルク エンド カンパニー インコーポレーテッド | ファルネシル―タンパク質転移酵素の阻害剤 |
| AU703203B2 (en) * | 1996-01-30 | 1999-03-18 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| AU715658B2 (en) * | 1996-04-03 | 2000-02-10 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| CA2250353A1 (en) * | 1996-04-03 | 1997-10-09 | Christopher J. Dinsmore | Inhibitors of farnesyl-protein transferase |
| US6063930A (en) * | 1996-04-03 | 2000-05-16 | Merck & Co., Inc. | Substituted imidazole compounds useful as farnesyl-protein transferase inhibitors |
| US6080870A (en) * | 1996-04-03 | 2000-06-27 | Merck & Co., Inc. | Biaryl substituted imidazole compounds useful as farnesyl-protein transferase inhibitors |
| US6858598B1 (en) | 1998-12-23 | 2005-02-22 | G. D. Searle & Co. | Method of using a matrix metalloproteinase inhibitor and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia |
| US6833373B1 (en) | 1998-12-23 | 2004-12-21 | G.D. Searle & Co. | Method of using an integrin antagonist and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia |
| SK14042003A3 (sk) | 2001-05-16 | 2004-05-04 | Novartis Ag | Kombinácia N-{5-[4-metylpiperazinometyl)benzoylamido]-2- metylfenyl}-4-(3-pyridyl)-2-pyrimidínamínu chemoterapeutického činidla a farmaceutický prostriedok, ktorý ju obsahuje |
| CN1325482C (zh) * | 2001-12-11 | 2007-07-11 | 埃默里大学 | 双(氰基苯基)甲基－三唑在预防乳腺癌中的用途 |
| ATE345790T1 (de) * | 2002-07-30 | 2006-12-15 | Novartis Pharma Gmbh | Kombination von einem aromatasehemmer mit einem bisphosphonat |
| GB0217636D0 (en) * | 2002-07-30 | 2002-09-11 | Novartis Ag | Organic compounds |
| JP2004196795A (ja) * | 2002-12-16 | 2004-07-15 | Wyeth | 外部寄生虫駆除剤としてのｎ−フェニル−３−シクロプロピルピラゾール−４−カルボニトリル |
| AU2003282380A1 (en) * | 2003-11-14 | 2004-06-06 | ADIBHATLA, KALI,SATYA, Bhujanga,rao | A method for the separation of the letrozole precursor 4-1-(1,2,4-triazolyl) methyl benzonitrile from its 1,3,4-triazolyl isomer |
| AR047144A1 (es) * | 2003-12-15 | 2006-01-11 | Theramex | Derivados de 1-n-fenilamino-1h-imidazol y composiciones farmaceuticas que los contienen |
| CA2608904A1 (en) * | 2005-07-06 | 2007-09-07 | Sicor Inc. | Improved process for the preparation of letrozole |
| GT200600381A (es) | 2005-08-25 | 2007-03-28 | Compuestos organicos | |
| US20090082413A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched letrozole |
| JP2013525296A (ja) | 2010-04-16 | 2013-06-20 | ノバルティス アーゲー | 内分泌療法抵抗性乳癌の処置 |
| US9150524B2 (en) | 2010-08-27 | 2015-10-06 | Generics [Uk] Limited | Pure intermediate |
| BR112014005434B1 (pt) * | 2011-09-08 | 2021-01-05 | Novartis Ag | Composições farmacêuticas compreendendo inibidor da aromatase 4,4'-[fluoro-(1h-1,2,4triazol-1-il)metilemo]bisbenzonitrila e seu método de preparação |
| CN104379163A (zh) | 2012-06-08 | 2015-02-25 | 霍夫曼-拉罗奇有限公司 | 用于治疗癌症的磷酸肌醇3激酶抑制剂化合物和化疗剂的突变选择性及组合 |
| WO2015022609A1 (en) | 2013-08-14 | 2015-02-19 | Novartis Ag | Combination therapy for the treatment of cancer |
| AR104068A1 (es) | 2015-03-26 | 2017-06-21 | Hoffmann La Roche | Combinaciones de un compuesto inhibidor de fosfoinosítido 3-cinasa y un compuesto inhibidor de cdk4/6 para el tratamiento del cáncer |
| GB201614179D0 (en) | 2016-08-19 | 2016-10-05 | Mereo Biopharma 2 Ltd | Dosage regimen for the treatment of endometriosis |
| BR112021001233A2 (pt) | 2018-07-23 | 2021-04-20 | F. Hoffmann-La Roche Ag | método para tratar câncer em um paciente, uso de uma quantidade terapeuticamente eficaz de gdc-0077 e quantidade terapeuticamente eficaz de gdc-0077 |
| JP2022504388A (ja) | 2018-10-08 | 2022-01-13 | エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト | Ｐｉ３ｋアルファ阻害剤およびメトホルミンを用いたがんの処置方法 |
| BR112022010806A2 (pt) | 2019-12-03 | 2022-08-23 | Genentech Inc | Métodos para tratar câncer de mama, para inibir o crescimento tumoral e para prevenir ou retardar o desenvolvimento de resistência de um câncer de mama |
| EP4259662A1 (en) | 2020-12-11 | 2023-10-18 | Genentech, Inc. | Combination therapies for treatment of her2 cancer |
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| US3290281A (en) * | 1963-07-18 | 1966-12-06 | Weinstein Julius | Photochromic nitrobenzylpyridines |
| US3397273A (en) * | 1966-02-18 | 1968-08-13 | Lilly Co Eli | Controlling phytopathogenic fungi on plants with 3-pyridyl methane derivatives |
| GB1170188A (en) * | 1967-09-15 | 1969-11-12 | Bayer Ag | N-trityl-imidazoles and salts and uses thereof |
| DE1670976B2 (de) * | 1968-01-29 | 1976-07-22 | N-trityl-imidazole | |
| DE1908991B2 (de) * | 1969-02-22 | 1977-05-26 | Bayer Ag, 5090 Leverkusen | Alpha, alpha-disubstituierte n- benzylimidazole und deren salze |
| BR6915465D0 (pt) * | 1969-03-07 | 1973-01-04 | Bayer Ag | Processo para preparar n-benzimidazois substituidos na posicao alfa por heterociclos penta-membrados com atividade antimicotica |
| DE2007794A1 (de) * | 1970-02-20 | 1971-09-02 | Farbenfabriken Bayer Aktiengesell schaft, 5090 Leverkusen | Fungizide Mittel |
| DE2009020C3 (de) * | 1970-02-26 | 1979-09-13 | Bayer Ag, 5090 Leverkusen | Verfahren zur Herstellung von N-(l,l,l-trisubstituierten)-Methylazolen |
| US3764690A (en) * | 1972-03-03 | 1973-10-09 | Bayer Ag | Substituted n-benzylimidazoles as antimycotic agents |
| US3927017A (en) * | 1974-06-27 | 1975-12-16 | Janssen Pharmaceutica Nv | 1-({62 -Aryl-{62 -R-ethyl)imidazoles |
| DE2628152C2 (de) * | 1976-06-23 | 1985-03-28 | Bayer Ag, 5090 Leverkusen | Fungizide und nematizide Mittel |
| DE2732531A1 (de) * | 1977-07-19 | 1979-02-01 | Hoechst Ag | Imidazolcarbonsaeuren und deren derivate |
| DE2735314A1 (de) * | 1977-08-05 | 1979-02-22 | Basf Ag | Alpha-azolylsulfide und deren derivate |
| US4431815A (en) * | 1977-08-26 | 1984-02-14 | Burroughs Wellcome Co. | 1-[3-(2,4-Dichlorophenyl)propyl]imidazole and salts thereof |
| EP0003732B1 (en) * | 1978-02-01 | 1983-10-19 | The Wellcome Foundation Limited | Imidazole derivatives and salts thereof, their synthesis, and pharmaceutical formulations thereof |
| DE2808086A1 (de) * | 1978-02-24 | 1979-08-30 | Bayer Ag | Substituierte diphenyl-imidazolyl- methane, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| DE2821829A1 (de) * | 1978-05-19 | 1979-11-22 | Basf Ag | Mittel zur regulierung des pflanzenwachstums |
| JPS55313A (en) * | 1978-06-13 | 1980-01-05 | Kissei Pharmaceut Co Ltd | Imidazole derivative |
| DE2847441A1 (de) | 1978-11-02 | 1980-05-22 | Basf Ag | Imidazol-kupferkomplexverbindungen |
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| US4281141A (en) * | 1980-05-30 | 1981-07-28 | Eli Lilly And Company | 3-(Imidazol-4-yl)-2-phenylpropanenitriles |
| US4617307A (en) * | 1984-06-20 | 1986-10-14 | Ciba-Geigy Corporation | Substituted imidazo[1,5-A]pyridine derivatives as aromatase inhibitors |
| US4562199A (en) * | 1983-08-11 | 1985-12-31 | Thorogood Peter B | Imidazole derivatives, compositions and use |
| EP0149976A3 (de) * | 1983-12-30 | 1986-12-10 | Ciba-Geigy Ag | Substituierte Imidazole |
| US4602025A (en) * | 1984-06-18 | 1986-07-22 | Eli Lilly And Company | Aromatase inhibitors |
| US4766140A (en) * | 1984-06-18 | 1988-08-23 | Eli Lilly And Company | Method of inhibiting aromatase |
| US4755526A (en) * | 1984-06-18 | 1988-07-05 | Eli Lilly And Company | Method of inhibiting aromatase |
| US4605661A (en) * | 1984-06-18 | 1986-08-12 | Eli Lilly And Company | Aromastase inhibiting α,α-diarylimidazole-4(5)-propionitriles, α,α-diarylimidazole-4(5)-propionamides, and 4(5)-(2,2-diarylethyl)imidazoles |
| US4801594A (en) * | 1984-06-18 | 1989-01-31 | Eli Lilly And Company | Aromatase inhibitors |
-
1986
- 1986-03-07 US US06/837,489 patent/US4749713A/en not_active Expired - Lifetime
-
1987
- 1987-03-02 FI FI870903A patent/FI91857C/fi not_active IP Right Cessation
- 1987-03-03 DD DD87300415A patent/DD264432A5/de not_active IP Right Cessation
- 1987-03-03 IL IL81746A patent/IL81746A/xx not_active IP Right Cessation
- 1987-03-04 DZ DZ870031A patent/DZ1055A1/fr active
- 1987-03-05 CY CY190587A patent/CY1905A/xx unknown
- 1987-03-05 EP EP87103099A patent/EP0236940B3/en not_active Expired - Lifetime
- 1987-03-05 RO RO1987134373A patent/RO101532B1/ro unknown
- 1987-03-05 PL PL1987280247A patent/PL152025B1/pl unknown
- 1987-03-05 DE DE87103099T patent/DE3787480T2/de not_active Expired - Lifetime
- 1987-03-05 CA CA000531185A patent/CA1316928C/en not_active Expired - Lifetime
- 1987-03-05 RO RO1987134372A patent/RO101533B1/ro unknown
- 1987-03-05 BG BG081514A patent/BG45700A3/xx unknown
- 1987-03-05 PL PL1987264460A patent/PL151490B1/pl unknown
- 1987-03-05 AT AT87103099T patent/ATE94873T1/de active
- 1987-03-05 BG BG081515A patent/BG45701A3/xx unknown
- 1987-03-05 HU HU87952A patent/HU202843B/hu unknown
- 1987-03-05 MA MA21124A patent/MA20888A1/fr unknown
- 1987-03-05 DE DE1997175016 patent/DE19775016I2/de active Active
- 1987-03-05 MC MC871874A patent/MC1805A1/xx unknown
- 1987-03-05 ES ES87103099T patent/ES2059317T3/es not_active Expired - Lifetime
- 1987-03-05 PT PT84410A patent/PT84410B/pt unknown
- 1987-03-05 BG BG078756A patent/BG46598A3/xx unknown
- 1987-03-06 KR KR1019870002004A patent/KR910000482B1/ko not_active IP Right Cessation
- 1987-03-06 SU SU874202145A patent/SU1470184A3/ru active
- 1987-03-06 ZA ZA871637A patent/ZA871637B/xx unknown
- 1987-03-06 MY MYPI87000247A patent/MY102428A/en unknown
- 1987-03-06 SK SK7368-87A patent/SK279103B6/sk unknown
- 1987-03-06 CZ CS877368A patent/CZ279028B6/cs not_active IP Right Cessation
- 1987-03-06 TN TNTNSN87033A patent/TNSN87033A1/fr unknown
- 1987-03-06 PH PH34986A patent/PH24159A/en unknown
- 1987-03-06 CZ CS871512A patent/CZ279026B6/cs not_active IP Right Cessation
- 1987-03-06 MX MX549687A patent/MX5496A/es unknown
- 1987-03-06 SK SK7367-87A patent/SK736787A3/sk unknown
- 1987-03-06 CZ CS877367A patent/CZ279027B6/cs not_active IP Right Cessation
- 1987-03-06 IE IE57587A patent/IE61101B1/en not_active IP Right Cessation
- 1987-03-06 NO NO870937A patent/NO170277C/no not_active IP Right Cessation
- 1987-03-06 SK SK1512-87A patent/SK151287A3/sk unknown
- 1987-03-06 JP JP62050446A patent/JPH0755930B2/ja not_active Expired - Lifetime
- 1987-03-06 MT MT998A patent/MTP998B/xx unknown
- 1987-03-06 DK DK117687A patent/DK172190B1/da not_active IP Right Cessation
-
1988
- 1988-01-18 SU SU884203990A patent/SU1549478A3/ru active
- 1988-01-18 SU SU884203999A patent/SU1577695A3/ru active
-
1993
- 1993-11-11 BG BG098212A patent/BG61204B2/bg unknown
-
1996
- 1996-03-21 HK HK50296A patent/HK50296A/xx not_active IP Right Cessation
- 1996-07-18 LV LV960274A patent/LV5769B4/xx unknown
-
1997
- 1997-03-03 NL NL970011C patent/NL970011I2/nl unknown
- 1997-08-20 LU LU90128C patent/LU90128I2/fr unknown
-
1998
- 1998-03-04 NO NO1998010C patent/NO1998010I1/no unknown
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