SK282359B6 - Substituovaný 1,2,3,4-tetrahydronaftalénový derivát, farmaceutická formulácia s jeho obsahom, jeho použitie, spôsob jeho prípravy a medziprodukty na jeho prípravu - Google Patents
Substituovaný 1,2,3,4-tetrahydronaftalénový derivát, farmaceutická formulácia s jeho obsahom, jeho použitie, spôsob jeho prípravy a medziprodukty na jeho prípravu Download PDFInfo
- Publication number
- SK282359B6 SK282359B6 SK1188-98A SK118898A SK282359B6 SK 282359 B6 SK282359 B6 SK 282359B6 SK 118898 A SK118898 A SK 118898A SK 282359 B6 SK282359 B6 SK 282359B6
- Authority
- SK
- Slovakia
- Prior art keywords
- tetrahydro
- naphthyl
- mmol
- methylpiperazin
- alkyl
- Prior art date
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- 239000008194 pharmaceutical composition Chemical class 0.000 title claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 title claims abstract 9
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical class C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 title claims description 6
- 239000000543 intermediate Substances 0.000 title abstract description 7
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims abstract description 126
- -1 piperazinyl-substituted 1,2,3,4-tetrahydronaphthalene Chemical class 0.000 claims abstract description 87
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 52
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 47
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 47
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 18
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 11
- 239000012458 free base Substances 0.000 claims abstract description 10
- 230000001404 mediated effect Effects 0.000 claims abstract description 10
- 125000003118 aryl group Chemical group 0.000 claims abstract description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 8
- 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 317
- 238000006243 chemical reaction Methods 0.000 claims description 120
- 238000000034 method Methods 0.000 claims description 52
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 45
- 239000001257 hydrogen Substances 0.000 claims description 34
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 150000002367 halogens Chemical class 0.000 claims description 25
- 125000003386 piperidinyl group Chemical group 0.000 claims description 19
- 125000006239 protecting group Chemical group 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 239000000460 chlorine Substances 0.000 claims description 17
- 150000002431 hydrogen Chemical class 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 208000035475 disorder Diseases 0.000 claims description 16
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
- 239000005557 antagonist Substances 0.000 claims description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 12
- 230000003213 activating effect Effects 0.000 claims description 10
- 239000004480 active ingredient Substances 0.000 claims description 10
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 10
- 125000004193 piperazinyl group Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 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 7
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 6
- 230000010933 acylation Effects 0.000 claims description 6
- 238000005917 acylation reaction Methods 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 208000007848 Alcoholism Diseases 0.000 claims description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 4
- 206010003805 Autism Diseases 0.000 claims description 4
- 208000020706 Autistic disease Diseases 0.000 claims description 4
- 208000032841 Bulimia Diseases 0.000 claims description 4
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 4
- 208000012661 Dyskinesia Diseases 0.000 claims description 4
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- 206010047163 Vasospasm Diseases 0.000 claims description 4
- 230000016571 aggressive behavior Effects 0.000 claims description 4
- 201000007930 alcohol dependence Diseases 0.000 claims description 4
- 230000029936 alkylation Effects 0.000 claims description 4
- 238000005804 alkylation reaction Methods 0.000 claims description 4
- 208000022531 anorexia Diseases 0.000 claims description 4
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 4
- 206010061428 decreased appetite Diseases 0.000 claims description 4
- 208000013403 hyperactivity Diseases 0.000 claims description 4
- 206010027599 migraine Diseases 0.000 claims description 4
- QXHVKAKZJIOEQA-HSZRJFAPSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-(morpholine-4-carbonyl)benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)C(=O)N1CCOCC1)CC2 QXHVKAKZJIOEQA-HSZRJFAPSA-N 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
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- 201000000980 schizophrenia Diseases 0.000 claims description 4
- 208000012201 sexual and gender identity disease Diseases 0.000 claims description 4
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- 230000001331 thermoregulatory effect Effects 0.000 claims description 4
- 230000004614 tumor growth Effects 0.000 claims description 4
- RZGVRNVEYZRHRR-JOCHJYFZSA-N 4-butoxy-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1=CC(OCCCC)=CC=C1C(=O)N[C@H]1CC2=C(N3CCN(C)CC3)C=CC=C2CC1 RZGVRNVEYZRHRR-JOCHJYFZSA-N 0.000 claims description 3
- XRTVUDGKOMELHO-RUZDIDTESA-N 4-cyclohexyl-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)C1CCCCC1)CC2 XRTVUDGKOMELHO-RUZDIDTESA-N 0.000 claims description 3
- MMPDQFMVQQHORI-LJQANCHMSA-N 4-fluoro-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(F)=CC=1)CC2 MMPDQFMVQQHORI-LJQANCHMSA-N 0.000 claims description 3
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- GBVSFRTVEHXDOF-UHFFFAOYSA-N n',n'-diethylbenzohydrazide Chemical compound CCN(CC)NC(=O)C1=CC=CC=C1 GBVSFRTVEHXDOF-UHFFFAOYSA-N 0.000 claims description 3
- FTCLFWOUOUOQEH-HSZRJFAPSA-N n-[(2r)-8-(4-ethylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(CC)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 FTCLFWOUOUOQEH-HSZRJFAPSA-N 0.000 claims description 3
- SXBQPRGLUJQYIZ-HSZRJFAPSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-3-phenoxybenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=C(OC=3C=CC=CC=3)C=CC=1)CC2 SXBQPRGLUJQYIZ-HSZRJFAPSA-N 0.000 claims description 3
- HWSWMVFTXFBDRW-JOCHJYFZSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 HWSWMVFTXFBDRW-JOCHJYFZSA-N 0.000 claims description 3
- VAQKVUSLQYAUDJ-JOCHJYFZSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-thiomorpholin-4-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCSCC1)CC2 VAQKVUSLQYAUDJ-JOCHJYFZSA-N 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 2
- YVOIVCHGVSLQBZ-XMMPIXPASA-N 4-morpholin-4-yl-n-[(2r)-8-(4-propylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1CN(CCC)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 YVOIVCHGVSLQBZ-XMMPIXPASA-N 0.000 claims description 2
- LLJAVORZMBIMFM-OAQYLSRUSA-N 4-n,4-n-dimethyl-1-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzene-1,4-dicarboxamide Chemical compound C1=CC(C(=O)N(C)C)=CC=C1C(=O)N[C@H]1CC2=C(N3CCN(C)CC3)C=CC=C2CC1 LLJAVORZMBIMFM-OAQYLSRUSA-N 0.000 claims description 2
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- 208000015114 central nervous system disease Diseases 0.000 claims description 2
- 238000010511 deprotection reaction Methods 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- KRMMIFCAVIETMC-HSZRJFAPSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-piperidin-1-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCCCC1)CC2 KRMMIFCAVIETMC-HSZRJFAPSA-N 0.000 claims description 2
- 125000006606 n-butoxy group Chemical group 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 150000003460 sulfonic acids Chemical class 0.000 claims description 2
- 208000025569 Tobacco Use disease Diseases 0.000 claims 3
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 2
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- FUKWTMJZHKZKFA-UHFFFAOYSA-N 4-cyanobenzamide Chemical compound NC(=O)C1=CC=C(C#N)C=C1 FUKWTMJZHKZKFA-UHFFFAOYSA-N 0.000 claims 1
- 230000006735 deficit Effects 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 510
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 444
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 266
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 213
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 210
- 239000002904 solvent Substances 0.000 description 172
- 239000000243 solution Substances 0.000 description 149
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 141
- 239000011541 reaction mixture Substances 0.000 description 132
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 129
- 239000000203 mixture Substances 0.000 description 128
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 122
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 120
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 118
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 117
- 239000003480 eluent Substances 0.000 description 104
- 239000000741 silica gel Substances 0.000 description 98
- 229910002027 silica gel Inorganic materials 0.000 description 98
- 229910052757 nitrogen Inorganic materials 0.000 description 94
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 93
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 88
- 239000011734 sodium Substances 0.000 description 86
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 82
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 78
- 239000012074 organic phase Substances 0.000 description 72
- 239000013078 crystal Substances 0.000 description 68
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 67
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- 239000012043 crude product Substances 0.000 description 66
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 65
- 238000003756 stirring Methods 0.000 description 59
- 239000012071 phase Substances 0.000 description 56
- 239000003921 oil Substances 0.000 description 54
- 235000019198 oils Nutrition 0.000 description 54
- 238000010992 reflux Methods 0.000 description 51
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 49
- 235000011114 ammonium hydroxide Nutrition 0.000 description 49
- 229920006395 saturated elastomer Polymers 0.000 description 48
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 44
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
- 239000000908 ammonium hydroxide Substances 0.000 description 38
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
- 239000002585 base Substances 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 36
- JKOKSUARGAQGCX-CYBMUJFWSA-N (2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](N)CC2 JKOKSUARGAQGCX-CYBMUJFWSA-N 0.000 description 35
- 238000000746 purification Methods 0.000 description 33
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 31
- 239000002253 acid Substances 0.000 description 27
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- 229910052727 yttrium Inorganic materials 0.000 description 27
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- 229960000583 acetic acid Drugs 0.000 description 23
- 239000007787 solid Substances 0.000 description 23
- 235000017557 sodium bicarbonate Nutrition 0.000 description 22
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 22
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 21
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 20
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- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 15
- 239000003054 catalyst Substances 0.000 description 15
- 125000002757 morpholinyl group Chemical group 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
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- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
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- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
- 125000005270 trialkylamine group Chemical group 0.000 description 12
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 11
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- 230000003197 catalytic effect Effects 0.000 description 11
- 239000003638 chemical reducing agent Substances 0.000 description 11
- 230000000638 stimulation Effects 0.000 description 11
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- 239000010410 layer Substances 0.000 description 10
- 239000012280 lithium aluminium hydride Substances 0.000 description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
- 239000012299 nitrogen atmosphere Substances 0.000 description 10
- 229910052697 platinum Inorganic materials 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- 239000000377 silicon dioxide Substances 0.000 description 10
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 9
- 239000012346 acetyl chloride Substances 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 239000001569 carbon dioxide Substances 0.000 description 9
- 229910002092 carbon dioxide Inorganic materials 0.000 description 9
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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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
- C07D295/08—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 bound oxygen or sulfur atoms
- C07D295/096—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 bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D295/135—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 separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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- 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
- C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
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- 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
- C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon 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
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- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
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- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no 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
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
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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
- C07D295/10—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 doubly bound oxygen or sulphur atoms
- C07D295/112—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 doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- 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
- C07D295/14—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D295/16—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 acylated on ring nitrogen atoms
- C07D295/20—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 acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D295/16—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 acylated on ring nitrogen atoms
- C07D295/20—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 acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/72—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 spiro-condensed with carbocyclic rings
-
- 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
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE9601110A SE9601110D0 (sv) | 1996-03-22 | 1996-03-22 | Substituted 1,2,3,4-tetrahydronaphthalene derivatives |
PCT/SE1997/000469 WO1997034883A1 (en) | 1996-03-22 | 1997-03-20 | Substituted 1,2,3,4-tetrahydronaphthalene derivatives |
Publications (2)
Publication Number | Publication Date |
---|---|
SK118898A3 SK118898A3 (en) | 1999-03-12 |
SK282359B6 true SK282359B6 (sk) | 2002-01-07 |
Family
ID=20401907
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK1188-98A SK282359B6 (sk) | 1996-03-22 | 1997-03-20 | Substituovaný 1,2,3,4-tetrahydronaftalénový derivát, farmaceutická formulácia s jeho obsahom, jeho použitie, spôsob jeho prípravy a medziprodukty na jeho prípravu |
Country Status (27)
Country | Link |
---|---|
US (2) | US6124283A (xx) |
EP (1) | EP0888319B1 (xx) |
JP (1) | JP2000506883A (xx) |
KR (1) | KR20000064751A (xx) |
CN (1) | CN1073101C (xx) |
AR (2) | AR006360A1 (xx) |
AT (1) | ATE231847T1 (xx) |
AU (1) | AU709856B2 (xx) |
BR (1) | BR9708093A (xx) |
CA (1) | CA2247940A1 (xx) |
CZ (1) | CZ301998A3 (xx) |
DE (1) | DE69718771T2 (xx) |
EE (1) | EE9800300A (xx) |
HR (1) | HRP970166A2 (xx) |
HU (1) | HUP9902454A3 (xx) |
ID (1) | ID16298A (xx) |
IL (2) | IL145681A0 (xx) |
IS (1) | IS4844A (xx) |
NO (1) | NO311803B1 (xx) |
NZ (1) | NZ331613A (xx) |
PL (1) | PL329121A1 (xx) |
SE (1) | SE9601110D0 (xx) |
SK (1) | SK282359B6 (xx) |
TR (1) | TR199801868T2 (xx) |
WO (1) | WO1997034883A1 (xx) |
YU (1) | YU40998A (xx) |
ZA (1) | ZA972056B (xx) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE9900190D0 (sv) * | 1999-01-22 | 1999-01-22 | Astra Ab | New compounds |
SE9702799D0 (sv) * | 1997-07-25 | 1997-07-25 | Astra Ab | New compounds |
SE9703375D0 (sv) * | 1997-09-18 | 1997-09-18 | Astra Ab | A new combination |
SE9703376D0 (sv) * | 1997-09-18 | 1997-09-18 | Astra Ab | A new combination |
SE9703374D0 (sv) * | 1997-09-18 | 1997-09-18 | Astra Ab | A new combination |
SE9703379D0 (sv) | 1997-09-18 | 1997-09-18 | Astra Ab | New compounds |
DK0952154T3 (da) | 1998-04-16 | 2004-12-13 | Pfizer Prod Inc | N-acyl- og N-aroylaralkylamider |
SE0002729D0 (sv) * | 2000-07-20 | 2000-07-20 | Astrazeneca Ab | Novel compound form |
CA2434152A1 (en) | 2001-01-16 | 2002-07-18 | Astrazeneca Ab | Therapeutic heterocyclic compounds |
IL156602A0 (en) | 2001-01-16 | 2004-01-04 | Astrazeneca Ab | Therapeutic chromone compounds |
WO2003007956A1 (en) | 2001-07-20 | 2003-01-30 | Psychogenics, Inc. | Treatment for attention-deficit hyperactivity disorder |
SE0301794D0 (sv) * | 2003-06-19 | 2003-06-19 | Astrazeneca Ab | New use III |
SE0301798D0 (sv) * | 2003-06-19 | 2003-06-19 | Astrazeneca Ab | New use IV |
CN101119965B (zh) * | 2004-12-21 | 2012-09-26 | 弗·哈夫曼-拉罗切有限公司 | 萘满和茚满衍生物及其用途 |
JP2009533325A (ja) * | 2006-03-17 | 2009-09-17 | アストラゼネカ・アクチエボラーグ | 5−ht6調節剤としての新規なテトラリン |
WO2008130319A2 (en) * | 2007-04-23 | 2008-10-30 | Astrazeneca Ab | Novel n-tetrahydronaphtalene or n-chromane carboxamide derivatives for the treatment of pain |
WO2008130321A2 (en) * | 2007-04-23 | 2008-10-30 | Astrazeneca Ab | Novel n-tetrahydronaphtalene or 5-heterocyclyl-chromane or 8-heterocyclyl-tetrahydronaphtalene derivatives for the treatment of pain |
WO2008130322A1 (en) * | 2007-04-23 | 2008-10-30 | Astrazeneca Ab | Novel 5-heterocyclyl-chromane derivatives for the treatment of pain |
SA08290245B1 (ar) * | 2007-04-23 | 2012-02-12 | استرازينيكا ايه بي | مشتقات كربو كساميد جديدة من -n (8-اريل رباعي هيدرو نفثالين غير متجانس- 2- يل) أو -n (5-اريل كرومان غير متجانس -3-يل) لعلاج الألم |
WO2008130323A1 (en) * | 2007-04-23 | 2008-10-30 | Astrazeneca Ab | Novel 8-piperazine-tetrahydronaphtalene derivatives for the treatment of pain |
EP2098511A1 (en) | 2008-03-07 | 2009-09-09 | Solvias AG | Process for preparing compounds containing a hydronaphtalene structure with an unsymmetrically substituted benzene ring |
JP6888827B2 (ja) * | 2015-05-19 | 2021-06-16 | ノースイースタン ユニバーシティ | 末梢におけるセロトニン受容体をモジュレートするための化合物または方法 |
WO2020183011A1 (en) | 2019-03-14 | 2020-09-17 | Institut Curie | Htr1d inhibitors and uses thereof in the treatment of cancer |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3919624A1 (de) * | 1989-06-15 | 1990-12-20 | Boehringer Ingelheim Kg | Neue 2,5-diaminotetraline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
DE69218813T2 (de) * | 1991-02-08 | 1997-08-14 | Lilly Co Eli | Ringsubstituierte 2-Amino-1,2,3,4-tetrahydronaphthaline |
DE69232003T2 (de) * | 1991-09-18 | 2002-04-25 | Glaxo Group Ltd | Benzanilidderivate als 5-HT1D-Antagonisten |
GB9119920D0 (en) * | 1991-09-18 | 1991-10-30 | Glaxo Group Ltd | Chemical compounds |
GB9119932D0 (en) * | 1991-09-18 | 1991-10-30 | Glaxo Group Ltd | Chemical compounds |
DK148392D0 (da) * | 1992-12-09 | 1992-12-09 | Lundbeck & Co As H | Heterocykliske forbindelser |
GB2273930A (en) * | 1992-12-30 | 1994-07-06 | Glaxo Group Ltd | Benzanilide derivatives |
CA2158457C (en) * | 1993-03-16 | 2001-04-17 | Bertrand Leo Chenard | Naphthalene derivatives |
SE9301732D0 (sv) * | 1993-05-18 | 1993-05-18 | Haakan Wilhelm Wikstroem | New centrally acting 5-,6-,7-, and 8-substituted sulphone esters of n-monosubstituted 2-aminotetralins |
JPH09503773A (ja) * | 1993-10-19 | 1997-04-15 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | 5ht−1dレセプター拮抗剤用のベンズアニリド誘導体 |
SE9702799D0 (sv) * | 1997-07-25 | 1997-07-25 | Astra Ab | New compounds |
SE9703374D0 (sv) * | 1997-09-18 | 1997-09-18 | Astra Ab | A new combination |
SE9703376D0 (sv) * | 1997-09-18 | 1997-09-18 | Astra Ab | A new combination |
SE9703375D0 (sv) * | 1997-09-18 | 1997-09-18 | Astra Ab | A new combination |
-
1996
- 1996-03-22 SE SE9601110A patent/SE9601110D0/xx unknown
-
1997
- 1997-03-10 ZA ZA9702056A patent/ZA972056B/xx unknown
- 1997-03-20 TR TR1998/01868T patent/TR199801868T2/xx unknown
- 1997-03-20 AT AT97914727T patent/ATE231847T1/de not_active IP Right Cessation
- 1997-03-20 WO PCT/SE1997/000469 patent/WO1997034883A1/en not_active Application Discontinuation
- 1997-03-20 US US08/836,004 patent/US6124283A/en not_active Expired - Fee Related
- 1997-03-20 NZ NZ331613A patent/NZ331613A/xx unknown
- 1997-03-20 BR BR9708093A patent/BR9708093A/pt unknown
- 1997-03-20 KR KR1019980707506A patent/KR20000064751A/ko not_active Application Discontinuation
- 1997-03-20 EP EP97914727A patent/EP0888319B1/en not_active Expired - Lifetime
- 1997-03-20 EE EE9800300A patent/EE9800300A/xx unknown
- 1997-03-20 DE DE69718771T patent/DE69718771T2/de not_active Expired - Fee Related
- 1997-03-20 IL IL14568197A patent/IL145681A0/xx unknown
- 1997-03-20 PL PL97329121A patent/PL329121A1/xx unknown
- 1997-03-20 IL IL12607097A patent/IL126070A0/xx unknown
- 1997-03-20 CN CN97194726A patent/CN1073101C/zh not_active Expired - Fee Related
- 1997-03-20 HU HU9902454A patent/HUP9902454A3/hu unknown
- 1997-03-20 JP JP9533410A patent/JP2000506883A/ja not_active Ceased
- 1997-03-20 CZ CZ983019A patent/CZ301998A3/cs unknown
- 1997-03-20 AU AU21865/97A patent/AU709856B2/en not_active Ceased
- 1997-03-20 CA CA002247940A patent/CA2247940A1/en not_active Abandoned
- 1997-03-20 SK SK1188-98A patent/SK282359B6/sk unknown
- 1997-03-21 ID IDP970931A patent/ID16298A/id unknown
- 1997-03-21 AR ARP970101163A patent/AR006360A1/es not_active Application Discontinuation
- 1997-03-21 HR HR9601110-1A patent/HRP970166A2/xx not_active Application Discontinuation
- 1997-12-02 AR ARP970105660A patent/AR010080A1/es unknown
-
1998
- 1998-09-09 IS IS4844A patent/IS4844A/is unknown
- 1998-09-21 NO NO19984385A patent/NO311803B1/no not_active IP Right Cessation
- 1998-09-22 YU YU40998A patent/YU40998A/sh unknown
-
2000
- 2000-08-31 US US09/653,427 patent/US6410530B1/en not_active Expired - Fee Related
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