NO313670B1 - Nye forbindelser med analgetisk effekt, farmasöytisk preparat inneholdende slike forbindelser, deres anvendelse, fremgangsmåtefor deres fremstilling og mellomprodukter - Google Patents
Nye forbindelser med analgetisk effekt, farmasöytisk preparat inneholdende slike forbindelser, deres anvendelse, fremgangsmåtefor deres fremstilling og mellomprodukter Download PDFInfo
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- NO313670B1 NO313670B1 NO19993022A NO993022A NO313670B1 NO 313670 B1 NO313670 B1 NO 313670B1 NO 19993022 A NO19993022 A NO 19993022A NO 993022 A NO993022 A NO 993022A NO 313670 B1 NO313670 B1 NO 313670B1
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- 150000001875 compounds Chemical class 0.000 title claims description 165
- 238000002360 preparation method Methods 0.000 title claims description 90
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 7
- 238000000034 method Methods 0.000 title description 58
- 230000000202 analgesic effect Effects 0.000 title description 4
- 239000000543 intermediate Substances 0.000 title description 3
- 238000006243 chemical reaction Methods 0.000 claims description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 239000002904 solvent Substances 0.000 claims description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 29
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 208000002193 Pain Diseases 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 150000002576 ketones Chemical class 0.000 claims description 7
- 229910052751 metal Inorganic materials 0.000 claims description 7
- 239000002184 metal Substances 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 6
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 125000002524 organometallic group Chemical group 0.000 claims description 6
- 230000036407 pain Effects 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 229940126601 medicinal product Drugs 0.000 claims description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 150000001860 citric acid derivatives Chemical class 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 210000002820 sympathetic nervous system Anatomy 0.000 claims description 2
- 229940095064 tartrate Drugs 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 7
- 208000020339 Spinal injury Diseases 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229910021653 sulphate ion Inorganic materials 0.000 claims 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 84
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 76
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 67
- 238000005481 NMR spectroscopy Methods 0.000 description 53
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- 239000000243 solution Substances 0.000 description 50
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 49
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- 229910001868 water Inorganic materials 0.000 description 35
- 239000000460 chlorine Substances 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 238000004458 analytical method Methods 0.000 description 32
- -1 naltrindole Chemical class 0.000 description 31
- 150000003840 hydrochlorides Chemical class 0.000 description 27
- 239000002585 base Substances 0.000 description 26
- 235000019439 ethyl acetate Nutrition 0.000 description 26
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
- 101150041968 CDC13 gene Proteins 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000012043 crude product Substances 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 23
- 239000012267 brine Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
- 239000000203 mixture Substances 0.000 description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- SMUGAZNLKPFBSB-UHFFFAOYSA-N n,n-diethyl-4-[phenyl(piperidin-4-ylidene)methyl]benzamide Chemical compound C1=CC(C(=O)N(CC)CC)=CC=C1C(C=1C=CC=CC=1)=C1CCNCC1 SMUGAZNLKPFBSB-UHFFFAOYSA-N 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 239000000843 powder Substances 0.000 description 11
- 239000007787 solid 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
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- FZERHIULMFGESH-UHFFFAOYSA-N N-phenylacetamide Chemical compound CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 9
- 150000002170 ethers Chemical class 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 238000010828 elution Methods 0.000 description 8
- 210000002683 foot Anatomy 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 239000011877 solvent mixture Substances 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 150000002431 hydrogen Chemical class 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 239000002287 radioligand Substances 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- 239000007983 Tris buffer Substances 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 210000004209 hair Anatomy 0.000 description 6
- 229910052744 lithium Inorganic materials 0.000 description 6
- 239000011777 magnesium Substances 0.000 description 6
- 229910052749 magnesium Inorganic materials 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 5
- 229960001413 acetanilide Drugs 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 150000002440 hydroxy compounds Chemical class 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- GHOMPHXKTJFWCV-UHFFFAOYSA-N n,n-diethyl-4-iodobenzamide Chemical compound CCN(CC)C(=O)C1=CC=C(I)C=C1 GHOMPHXKTJFWCV-UHFFFAOYSA-N 0.000 description 5
- YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- BRAQYUZYDPJYAJ-UHFFFAOYSA-N tert-butyl 4-[bromo-[4-(diethylcarbamoyl)phenyl]methylidene]piperidine-1-carboxylate Chemical compound C1=CC(C(=O)N(CC)CC)=CC=C1C(Br)=C1CCN(C(=O)OC(C)(C)C)CC1 BRAQYUZYDPJYAJ-UHFFFAOYSA-N 0.000 description 5
- 229910052725 zinc Inorganic materials 0.000 description 5
- 239000011701 zinc Substances 0.000 description 5
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 4
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo(3.3.1)nonane Chemical compound C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 229910052684 Cerium Inorganic materials 0.000 description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 4
- AVYVHIKSFXVDBG-UHFFFAOYSA-N N-benzyl-N-hydroxy-2,2-dimethylbutanamide Chemical compound C(C1=CC=CC=C1)N(C(C(CC)(C)C)=O)O AVYVHIKSFXVDBG-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000006069 Suzuki reaction reaction Methods 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- ZMIGMASIKSOYAM-UHFFFAOYSA-N cerium Chemical compound [Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce] ZMIGMASIKSOYAM-UHFFFAOYSA-N 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 229940126214 compound 3 Drugs 0.000 description 4
- 229910052802 copper Inorganic materials 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- 230000018044 dehydration Effects 0.000 description 4
- 238000006297 dehydration reaction Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 210000003497 sciatic nerve Anatomy 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- 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 4
- KNXQDJCZSVHEIW-UHFFFAOYSA-N (3-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(F)=C1 KNXQDJCZSVHEIW-UHFFFAOYSA-N 0.000 description 3
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 3
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 3
- LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 description 3
- XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 3
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000000730 antalgic agent Substances 0.000 description 3
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- AXSKOCYPNPDUBP-UHFFFAOYSA-N tert-butyl 4-[[4-(diethylcarbamoyl)phenyl]-(3-fluorophenyl)-hydroxymethyl]piperidine-1-carboxylate Chemical compound C1=CC(C(=O)N(CC)CC)=CC=C1C(O)(C=1C=C(F)C=CC=1)C1CCN(C(=O)OC(C)(C)C)CC1 AXSKOCYPNPDUBP-UHFFFAOYSA-N 0.000 description 1
- DLHFPDSYUIXAGJ-UHFFFAOYSA-N tert-butyl 4-[[4-(diethylcarbamoyl)phenyl]-hydroxy-(3-methoxyphenyl)methyl]piperidine-1-carboxylate Chemical compound C1=CC(C(=O)N(CC)CC)=CC=C1C(O)(C=1C=C(OC)C=CC=1)C1CCN(C(=O)OC(C)(C)C)CC1 DLHFPDSYUIXAGJ-UHFFFAOYSA-N 0.000 description 1
- BMNZOIICOVXXQZ-UHFFFAOYSA-N tert-butyl 4-[[4-(ethoxycarbonylamino)phenyl]-(3-fluorophenyl)methyl]piperidine-1-carboxylate Chemical compound C1=CC(NC(=O)OCC)=CC=C1C(C=1C=C(F)C=CC=1)C1CCN(C(=O)OC(C)(C)C)CC1 BMNZOIICOVXXQZ-UHFFFAOYSA-N 0.000 description 1
- YBFZDPLCKXRXHS-UHFFFAOYSA-N tert-butyl 4-[bromo-[4-(ethoxycarbonylamino)phenyl]methyl]piperidine-1-carboxylate Chemical compound C1=CC(NC(=O)OCC)=CC=C1C(Br)C1CCN(C(=O)OC(C)(C)C)CC1 YBFZDPLCKXRXHS-UHFFFAOYSA-N 0.000 description 1
- NNGSDTSXCBMPJX-UHFFFAOYSA-N tert-butyl 4-[bromo-[4-(piperidine-1-carbonyl)phenyl]methylidene]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1=C(Br)C1=CC=C(C(=O)N2CCCCC2)C=C1 NNGSDTSXCBMPJX-UHFFFAOYSA-N 0.000 description 1
- BWUILNMXUUMHPV-UHFFFAOYSA-N tert-butyl 4-bromo-4-[bromo-(4-methoxycarbonylphenyl)methyl]piperidine-1-carboxylate Chemical compound C1=CC(C(=O)OC)=CC=C1C(Br)C1(Br)CCN(C(=O)OC(C)(C)C)CC1 BWUILNMXUUMHPV-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- ZXUCBXRTRRIBSO-UHFFFAOYSA-L tetrabutylazanium;sulfate Chemical compound [O-]S([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC ZXUCBXRTRRIBSO-UHFFFAOYSA-L 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
- QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
- 210000003371 toe Anatomy 0.000 description 1
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- 235000010487 tragacanth Nutrition 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000006478 transmetalation reaction Methods 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- 229950009811 ubenimex Drugs 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 208000009935 visceral pain Diseases 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229910001845 yogo sapphire Inorganic materials 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D211/68—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 one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—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 one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/80—Radicals substituted by oxygen atoms
-
- 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
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE9604785A SE9604785D0 (sv) | 1996-12-20 | 1996-12-20 | New compounds |
SE9702535A SE9702535D0 (sv) | 1997-07-01 | 1997-07-01 | New compounds |
PCT/SE1997/002050 WO1998028275A1 (en) | 1996-12-20 | 1997-12-09 | Novel compounds with analgesic effect |
Publications (3)
Publication Number | Publication Date |
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NO993022D0 NO993022D0 (no) | 1999-06-18 |
NO993022L NO993022L (no) | 1999-08-20 |
NO313670B1 true NO313670B1 (no) | 2002-11-11 |
Family
ID=26662830
Family Applications (1)
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NO19993022A NO313670B1 (no) | 1996-12-20 | 1999-06-18 | Nye forbindelser med analgetisk effekt, farmasöytisk preparat inneholdende slike forbindelser, deres anvendelse, fremgangsmåtefor deres fremstilling og mellomprodukter |
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Country | Link |
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US (5) | US6187792B1 (pt) |
EP (1) | EP0946511B1 (pt) |
JP (1) | JP4324652B2 (pt) |
KR (1) | KR100549144B1 (pt) |
CN (2) | CN1146540C (pt) |
AR (1) | AR010376A1 (pt) |
AT (1) | ATE296288T1 (pt) |
AU (1) | AU737999B2 (pt) |
BR (1) | BR9714055B1 (pt) |
CA (1) | CA2274074C (pt) |
CZ (1) | CZ295557B6 (pt) |
DE (1) | DE69733362T2 (pt) |
EE (1) | EE03824B1 (pt) |
ES (1) | ES2241060T3 (pt) |
HK (1) | HK1022689A1 (pt) |
HU (1) | HU226724B1 (pt) |
ID (1) | ID22074A (pt) |
IL (2) | IL130535A0 (pt) |
IS (1) | IS2210B (pt) |
MY (1) | MY119403A (pt) |
NO (1) | NO313670B1 (pt) |
NZ (1) | NZ336029A (pt) |
PL (1) | PL189196B1 (pt) |
PT (1) | PT946511E (pt) |
RU (1) | RU2193029C2 (pt) |
SK (1) | SK283211B6 (pt) |
TR (1) | TR199901417T2 (pt) |
TW (1) | TW548271B (pt) |
WO (1) | WO1998028275A1 (pt) |
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SE9904674D0 (sv) | 1999-12-20 | 1999-12-20 | Astra Pharma Inc | Novel compounds |
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AU4274401A (en) | 2000-03-24 | 2001-10-03 | Meiji Seika Kaisha | Diphenylalkylamine derivatives useful as opioid delta receptor agonists |
SE0001207D0 (sv) * | 2000-04-04 | 2000-04-04 | Astrazeneca Canada Inc | Novel compounds |
SE0001208D0 (sv) * | 2000-04-04 | 2000-04-04 | Astrazeneca Canada Inc | Novel compounds |
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AU2001216218A1 (en) | 2000-05-25 | 2001-12-11 | Sepracor, Inc. | Heterocyclic analgesic compounds and method of use thereof |
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SE0101767D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
SE0101769D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
BR0209678A (pt) | 2001-05-18 | 2004-09-14 | Astrazeneca Ab | Composto, processo para preparar e uso do mesmo, composição farmacêutica, e, métodos para o tratamento da dor e de distúrbios gastrintestinais funcionais |
SE0101773D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
SE0101765D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
SE0101770D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
SE0101771D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
SE0101768D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
SE0101766D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
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US8575169B2 (en) * | 2001-10-29 | 2013-11-05 | Versi Group, Llc | Method of treating sexual dysfunctions with delta opioid receptor agonist compounds |
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SE0301441D0 (sv) * | 2003-05-16 | 2003-05-16 | Astrazeneca Ab | Diarylmethylidene piperidine derivatives, preparations thereof and uses thereof |
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-
1997
- 1997-12-08 TW TW086118465A patent/TW548271B/zh not_active IP Right Cessation
- 1997-12-09 EP EP97950538A patent/EP0946511B1/en not_active Expired - Lifetime
- 1997-12-09 CZ CZ19992199A patent/CZ295557B6/cs not_active IP Right Cessation
- 1997-12-09 HU HU0000610A patent/HU226724B1/hu not_active IP Right Cessation
- 1997-12-09 ES ES97950538T patent/ES2241060T3/es not_active Expired - Lifetime
- 1997-12-09 CN CNB971818142A patent/CN1146540C/zh not_active Expired - Fee Related
- 1997-12-09 KR KR1019997005585A patent/KR100549144B1/ko not_active IP Right Cessation
- 1997-12-09 US US09/029,633 patent/US6187792B1/en not_active Expired - Lifetime
- 1997-12-09 DE DE69733362T patent/DE69733362T2/de not_active Expired - Lifetime
- 1997-12-09 TR TR1999/01417T patent/TR199901417T2/xx unknown
- 1997-12-09 ID IDW990508A patent/ID22074A/id unknown
- 1997-12-09 CA CA002274074A patent/CA2274074C/en not_active Expired - Fee Related
- 1997-12-09 RU RU99115750/04A patent/RU2193029C2/ru not_active IP Right Cessation
- 1997-12-09 PL PL97334374A patent/PL189196B1/pl not_active IP Right Cessation
- 1997-12-09 CN CNB2004100082366A patent/CN100519528C/zh not_active Expired - Fee Related
- 1997-12-09 NZ NZ336029A patent/NZ336029A/en unknown
- 1997-12-09 AU AU53512/98A patent/AU737999B2/en not_active Ceased
- 1997-12-09 AT AT97950538T patent/ATE296288T1/de not_active IP Right Cessation
- 1997-12-09 SK SK762-99A patent/SK283211B6/sk not_active IP Right Cessation
- 1997-12-09 JP JP52866998A patent/JP4324652B2/ja not_active Expired - Fee Related
- 1997-12-09 EE EEP199900256A patent/EE03824B1/xx not_active IP Right Cessation
- 1997-12-09 IL IL13053597A patent/IL130535A0/xx active IP Right Grant
- 1997-12-09 WO PCT/SE1997/002050 patent/WO1998028275A1/en active IP Right Grant
- 1997-12-09 BR BRPI9714055-4A patent/BR9714055B1/pt not_active IP Right Cessation
- 1997-12-09 PT PT97950538T patent/PT946511E/pt unknown
- 1997-12-19 AR ARP970106074A patent/AR010376A1/es active IP Right Grant
- 1997-12-19 MY MYPI97006173A patent/MY119403A/en unknown
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1999
- 1999-06-07 IS IS5071A patent/IS2210B/is unknown
- 1999-06-17 IL IL130535A patent/IL130535A/en not_active IP Right Cessation
- 1999-06-18 NO NO19993022A patent/NO313670B1/no not_active IP Right Cessation
-
2000
- 2000-03-11 HK HK00101528A patent/HK1022689A1/xx not_active IP Right Cessation
-
2001
- 2001-01-18 US US09/761,833 patent/US6455545B2/en not_active Expired - Fee Related
-
2002
- 2002-08-19 US US10/222,990 patent/US6693117B2/en not_active Expired - Fee Related
-
2003
- 2003-12-09 US US10/730,265 patent/US7312336B2/en not_active Expired - Fee Related
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2007
- 2007-12-05 US US11/951,014 patent/US20080176903A1/en not_active Abandoned
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