NO321405B1 - Adamantanderivater, fremgangsmate for fremstilling derav, farmasoytisk preparat og fremgangsmate for fremstilling derav, samt deres anvendelse i terapi. - Google Patents
Adamantanderivater, fremgangsmate for fremstilling derav, farmasoytisk preparat og fremgangsmate for fremstilling derav, samt deres anvendelse i terapi. Download PDFInfo
- Publication number
- NO321405B1 NO321405B1 NO20014894A NO20014894A NO321405B1 NO 321405 B1 NO321405 B1 NO 321405B1 NO 20014894 A NO20014894 A NO 20014894A NO 20014894 A NO20014894 A NO 20014894A NO 321405 B1 NO321405 B1 NO 321405B1
- Authority
- NO
- Norway
- Prior art keywords
- ylmethyl
- dec
- chloro
- benzamide
- formula
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 35
- 238000002360 preparation method Methods 0.000 title claims description 9
- 230000008569 process Effects 0.000 title claims description 5
- 238000002560 therapeutic procedure Methods 0.000 title claims description 5
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical class C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 title description 3
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 385
- -1 cyano, nitro, amino, hydroxyl Chemical group 0.000 claims description 127
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 91
- 239000000203 mixture Substances 0.000 claims description 72
- 238000006243 chemical reaction Methods 0.000 claims description 61
- 150000003839 salts Chemical class 0.000 claims description 61
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 55
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 48
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 45
- SNIABFMMCKVXSY-UHFFFAOYSA-N benzoylazanium;chloride Chemical class Cl.NC(=O)C1=CC=CC=C1 SNIABFMMCKVXSY-UHFFFAOYSA-N 0.000 claims description 38
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 36
- 239000002585 base Substances 0.000 claims description 33
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 27
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 20
- 239000003153 chemical reaction reagent Substances 0.000 claims description 19
- 239000012453 solvate Substances 0.000 claims description 19
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 claims description 19
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 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 16
- 229920006395 saturated elastomer Polymers 0.000 claims description 16
- 125000001931 aliphatic group Chemical group 0.000 claims description 14
- 238000006722 reduction reaction Methods 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 125000001153 fluoro group Chemical group F* 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 13
- 229910052763 palladium Inorganic materials 0.000 claims description 13
- 239000003054 catalyst Substances 0.000 claims description 12
- 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 11
- 101150047356 dec-1 gene Proteins 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 10
- 125000001979 organolithium group Chemical group 0.000 claims description 9
- 230000003647 oxidation Effects 0.000 claims description 9
- 238000007254 oxidation reaction Methods 0.000 claims description 9
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 239000007822 coupling agent Substances 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 239000012312 sodium hydride Substances 0.000 claims description 7
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 6
- 239000003638 chemical reducing agent Substances 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 claims description 5
- 101100400378 Mus musculus Marveld2 gene Proteins 0.000 claims description 5
- 101100073357 Streptomyces halstedii sch2 gene Proteins 0.000 claims description 5
- 159000000021 acetate salts Chemical class 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 239000003446 ligand Substances 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 claims description 5
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- PPNCOQHHSGMKGI-UHFFFAOYSA-N 1-cyclononyldiazonane Chemical group C1CCCCCCCC1N1NCCCCCCC1 PPNCOQHHSGMKGI-UHFFFAOYSA-N 0.000 claims description 3
- JWANTWYZEGLGHM-UHFFFAOYSA-N C1CCCCCCCC1N1ONCCCCCC1 Chemical group C1CCCCCCCC1N1ONCCCCCC1 JWANTWYZEGLGHM-UHFFFAOYSA-N 0.000 claims description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 3
- 230000000414 obstructive effect Effects 0.000 claims description 3
- 208000023504 respiratory system disease Diseases 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 3
- OQJBFFCUFALWQL-BUHFOSPRSA-N (ne)-n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)\N=N\C(=O)N1CCCCC1 OQJBFFCUFALWQL-BUHFOSPRSA-N 0.000 claims description 2
- DWKUKQRKVCMOLP-UHFFFAOYSA-N 1-piperideine Chemical compound C1CCN=CC1 DWKUKQRKVCMOLP-UHFFFAOYSA-N 0.000 claims description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 claims description 2
- 206010008583 Chloroma Diseases 0.000 claims description 2
- 208000032544 Cicatrix Diseases 0.000 claims description 2
- 244000194101 Ginkgo biloba Species 0.000 claims description 2
- 235000008100 Ginkgo biloba Nutrition 0.000 claims description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 2
- 125000003172 aldehyde group Chemical group 0.000 claims description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 125000005053 dihydropyrimidinyl group Chemical group N1(CN=CC=C1)* 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 238000005984 hydrogenation reaction Methods 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- KSGPQSJEDYGCSV-UHFFFAOYSA-N n-(1-adamantylmethyl)-2-chloro-4-(1,4-diazepan-1-yl)benzamide Chemical compound C=1C=C(C(=O)NCC23CC4CC(CC(C4)C2)C3)C(Cl)=CC=1N1CCCNCC1 KSGPQSJEDYGCSV-UHFFFAOYSA-N 0.000 claims description 2
- KUAUAHIBDBUVFD-UHFFFAOYSA-N n-(1-adamantylmethyl)-2-chloro-4-piperidin-3-yloxybenzamide Chemical compound C=1C=C(C(=O)NCC23CC4CC(CC(C4)C2)C3)C(Cl)=CC=1OC1CCCNC1 KUAUAHIBDBUVFD-UHFFFAOYSA-N 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 2
- 125000005936 piperidyl group Chemical group 0.000 claims description 2
- 231100000241 scar Toxicity 0.000 claims description 2
- 230000037387 scars Effects 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 230000007306 turnover Effects 0.000 claims description 2
- MABDVMXVGUHZJK-UHFFFAOYSA-N 2-(1-adamantyl)-n-(2-methyl-4-piperazin-1-ylphenyl)acetamide Chemical compound C=1C=C(NC(=O)CC23CC4CC(CC(C4)C2)C3)C(C)=CC=1N1CCNCC1 MABDVMXVGUHZJK-UHFFFAOYSA-N 0.000 claims 1
- SDXWQAGJFKGHQL-UHFFFAOYSA-N 2-(1-adamantyl)-n-(2-methyl-5-piperidin-4-yloxyphenyl)acetamide Chemical compound C1=C(NC(=O)CC23CC4CC(CC(C4)C2)C3)C(C)=CC=C1OC1CCNCC1 SDXWQAGJFKGHQL-UHFFFAOYSA-N 0.000 claims 1
- DOURJPOQARHJKG-UHFFFAOYSA-N 2-(1-adamantylmethyl)benzamide Chemical compound NC(=O)C1=CC=CC=C1CC1(C2)CC(C3)CC2CC3C1 DOURJPOQARHJKG-UHFFFAOYSA-N 0.000 claims 1
- BCOSELLBHSZWAB-PQODNNDASA-N C1C[C@@H](N)CC[C@@H]1OC1=CC=C(Cl)C(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1 Chemical compound C1C[C@@H](N)CC[C@@H]1OC1=CC=C(Cl)C(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1 BCOSELLBHSZWAB-PQODNNDASA-N 0.000 claims 1
- 229910052782 aluminium Inorganic materials 0.000 claims 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims 1
- 150000004678 hydrides Chemical class 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- RXINQFOYRWBBBU-UHFFFAOYSA-N n-(1-adamantylmethyl)-2-bromo-5-[[4-(2-hydroxyethylamino)piperidin-1-yl]methyl]benzamide Chemical compound C1CC(NCCO)CCN1CC1=CC=C(Br)C(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1 RXINQFOYRWBBBU-UHFFFAOYSA-N 0.000 claims 1
- PLHUEBVJMCGNDN-UHFFFAOYSA-N n-(1-adamantylmethyl)-2-chloro-3-piperazin-1-ylbenzamide Chemical compound C1=CC=C(C(=O)NCC23CC4CC(CC(C4)C2)C3)C(Cl)=C1N1CCNCC1 PLHUEBVJMCGNDN-UHFFFAOYSA-N 0.000 claims 1
- OXQVQNQTPUBRKB-UHFFFAOYSA-N n-(1-adamantylmethyl)-2-chloro-5-(piperidin-3-ylmethyl)benzamide Chemical compound C1=C(C(=O)NCC23CC4CC(CC(C4)C2)C3)C(Cl)=CC=C1CC1CCCNC1 OXQVQNQTPUBRKB-UHFFFAOYSA-N 0.000 claims 1
- VPHJZPZBRPTDJE-UHFFFAOYSA-N n-(1-adamantylmethyl)-2-chloro-5-(piperidin-4-ylmethyl)benzamide Chemical compound C1=C(C(=O)NCC23CC4CC(CC(C4)C2)C3)C(Cl)=CC=C1CC1CCNCC1 VPHJZPZBRPTDJE-UHFFFAOYSA-N 0.000 claims 1
- PCPXFLGWZCNHFP-UHFFFAOYSA-N n-(1-adamantylmethyl)-2-chloro-5-(piperidine-4-carbonyl)benzamide Chemical compound C1=C(C(=O)NCC23CC4CC(CC(C4)C2)C3)C(Cl)=CC=C1C(=O)C1CCNCC1 PCPXFLGWZCNHFP-UHFFFAOYSA-N 0.000 claims 1
- PYEBWMGLFSFLDW-UHFFFAOYSA-N n-(1-adamantylmethyl)-2-chloro-5-[2-(2-piperazin-1-ylethoxy)ethoxy]benzamide Chemical compound C1=C(C(=O)NCC23CC4CC(CC(C4)C2)C3)C(Cl)=CC=C1OCCOCCN1CCNCC1 PYEBWMGLFSFLDW-UHFFFAOYSA-N 0.000 claims 1
- KDWCIYRTTOPTND-UHFFFAOYSA-N n-(1-adamantylmethyl)-2-chloro-5-[hydroxy(piperidin-3-yl)methyl]benzamide Chemical compound C=1C=C(Cl)C(C(=O)NCC23CC4CC(CC(C4)C2)C3)=CC=1C(O)C1CCCNC1 KDWCIYRTTOPTND-UHFFFAOYSA-N 0.000 claims 1
- GOZAACCHTPXEPB-UHFFFAOYSA-N n-(1-adamantylmethyl)-2-chloro-5-[hydroxy(piperidin-4-yl)methyl]benzamide Chemical compound C=1C=C(Cl)C(C(=O)NCC23CC4CC(CC(C4)C2)C3)=CC=1C(O)C1CCNCC1 GOZAACCHTPXEPB-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 289
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 273
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 201
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 191
- 239000000243 solution Substances 0.000 description 179
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 160
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 132
- 238000005481 NMR spectroscopy Methods 0.000 description 100
- 239000007787 solid Substances 0.000 description 79
- 230000002829 reductive effect Effects 0.000 description 76
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 71
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 67
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- 239000011541 reaction mixture Substances 0.000 description 57
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 52
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
- 239000006260 foam Substances 0.000 description 38
- 239000000741 silica gel Substances 0.000 description 34
- 229910002027 silica gel Inorganic materials 0.000 description 34
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 34
- 239000000843 powder Substances 0.000 description 33
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 31
- 235000019341 magnesium sulphate Nutrition 0.000 description 31
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 30
- 239000002904 solvent Substances 0.000 description 27
- 238000004587 chromatography analysis Methods 0.000 description 26
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 26
- 239000012299 nitrogen atmosphere Substances 0.000 description 25
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 24
- 239000012044 organic layer Substances 0.000 description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 22
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- 239000012267 brine Substances 0.000 description 20
- 239000000706 filtrate Substances 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 19
- 239000010410 layer Substances 0.000 description 19
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 17
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 17
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 16
- 239000000284 extract Substances 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 15
- 229910000024 caesium carbonate Inorganic materials 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 238000010898 silica gel chromatography Methods 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- 239000013058 crude material Substances 0.000 description 13
- 238000001914 filtration Methods 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 13
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- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000004634 pharmacological analysis method Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 1
- VUNPWIPIOOMCPT-UHFFFAOYSA-N piperidin-3-ylmethanol Chemical compound OCC1CCCNC1 VUNPWIPIOOMCPT-UHFFFAOYSA-N 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 239000001120 potassium sulphate Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- ZAGOXLIWUBVBBZ-UHFFFAOYSA-N pyrazin-2-yloxyboronic acid Chemical compound OB(O)OC1=CN=CC=N1 ZAGOXLIWUBVBBZ-UHFFFAOYSA-N 0.000 description 1
- 235000007682 pyridoxal 5'-phosphate Nutrition 0.000 description 1
- 239000011589 pyridoxal 5'-phosphate Substances 0.000 description 1
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 1
- 229960001327 pyridoxal phosphate Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- NSILYQWHARROMG-UHFFFAOYSA-N tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNC(CO)C1 NSILYQWHARROMG-UHFFFAOYSA-N 0.000 description 1
- CMIBWIAICVBURI-UHFFFAOYSA-N tert-butyl 3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)C1 CMIBWIAICVBURI-UHFFFAOYSA-N 0.000 description 1
- DJXLXFWWETVERO-UHFFFAOYSA-N tert-butyl 4-(3-methyl-4-nitrophenyl)piperazine-1-carboxylate Chemical compound C1=C([N+]([O-])=O)C(C)=CC(N2CCN(CC2)C(=O)OC(C)(C)C)=C1 DJXLXFWWETVERO-UHFFFAOYSA-N 0.000 description 1
- VVQHZVVDJPYECU-UHFFFAOYSA-N tert-butyl 4-(4-amino-3-methylphenyl)piperazine-1-carboxylate Chemical compound C1=C(N)C(C)=CC(N2CCN(CC2)C(=O)OC(C)(C)C)=C1 VVQHZVVDJPYECU-UHFFFAOYSA-N 0.000 description 1
- HPQKDFGMQIQJHK-UHFFFAOYSA-N tert-butyl 4-(4-chloro-3-ethoxycarbonylphenyl)-1,4-diazepane-1-carboxylate Chemical compound C1=C(Cl)C(C(=O)OCC)=CC(N2CCN(CCC2)C(=O)OC(C)(C)C)=C1 HPQKDFGMQIQJHK-UHFFFAOYSA-N 0.000 description 1
- RSMNYTJCWIDZAH-UHFFFAOYSA-N tert-butyl 4-(iodomethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CI)CC1 RSMNYTJCWIDZAH-UHFFFAOYSA-N 0.000 description 1
- YFWQFKUQVJNPKP-UHFFFAOYSA-N tert-butyl 4-iodopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(I)CC1 YFWQFKUQVJNPKP-UHFFFAOYSA-N 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- SBUKINULYZANSP-UHFFFAOYSA-N tert-butyl n-(3-hydroxycyclopentyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(O)C1 SBUKINULYZANSP-UHFFFAOYSA-N 0.000 description 1
- FEYLUKDSKVSMSZ-UHFFFAOYSA-N tert-butyl n-(4-aminocyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(N)CC1 FEYLUKDSKVSMSZ-UHFFFAOYSA-N 0.000 description 1
- QZPWMJDAYANOCI-UHFFFAOYSA-N tert-butyl n-[1-[3-(1-adamantylmethylcarbamoyl)-4-chlorophenyl]piperidin-4-yl]carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCN1C1=CC=C(Cl)C(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1 QZPWMJDAYANOCI-UHFFFAOYSA-N 0.000 description 1
- DQQJBEAXSOOCPG-UHFFFAOYSA-N tert-butyl n-pyrrolidin-3-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNC1 DQQJBEAXSOOCPG-UHFFFAOYSA-N 0.000 description 1
- RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- VXKWYPOMXBVZSJ-UHFFFAOYSA-N tetramethyltin Chemical compound C[Sn](C)(C)C VXKWYPOMXBVZSJ-UHFFFAOYSA-N 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
- 208000027185 varicose disease Diseases 0.000 description 1
Classifications
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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
- C07D295/18—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 carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
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- A—HUMAN NECESSITIES
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/46—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/30—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having 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
- C07D207/12—Oxygen or sulfur atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having 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
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
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- 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
- C07D211/08—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
- C07D211/10—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 radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—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 radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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- 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
- C07D211/08—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
- C07D211/20—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 singly bound oxygen or sulphur atoms
- C07D211/22—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 singly bound oxygen or sulphur atoms by oxygen atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/42—Oxygen atoms attached in position 3 or 5
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- 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
-
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- 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
- C07D211/56—Nitrogen atoms
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/08—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
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- 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
- C07D295/08—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
- C07D295/084—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 attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—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 attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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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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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
- C07C2603/74—Adamantanes
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Steroid Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Hydrogenated Pyridines (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE9901270A SE9901270D0 (sv) | 1999-04-09 | 1999-04-09 | Novel compounds |
GB0002330A GB0002330D0 (en) | 2000-02-01 | 2000-02-01 | Novel compounds |
PCT/SE2000/000663 WO2000061569A1 (en) | 1999-04-09 | 2000-04-06 | Adamantane derivatives |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20014894D0 NO20014894D0 (no) | 2001-10-08 |
NO20014894L NO20014894L (no) | 2001-12-10 |
NO321405B1 true NO321405B1 (no) | 2006-05-08 |
Family
ID=26243543
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20014894A NO321405B1 (no) | 1999-04-09 | 2001-10-08 | Adamantanderivater, fremgangsmate for fremstilling derav, farmasoytisk preparat og fremgangsmate for fremstilling derav, samt deres anvendelse i terapi. |
Country Status (24)
Country | Link |
---|---|
US (1) | US6492355B1 (es) |
EP (1) | EP1171432A1 (es) |
JP (1) | JP2002541249A (es) |
KR (1) | KR100710091B1 (es) |
CN (1) | CN1147483C (es) |
AR (1) | AR023423A1 (es) |
AU (1) | AU774526B2 (es) |
BR (1) | BR0009651A (es) |
CA (1) | CA2368829A1 (es) |
CZ (1) | CZ20013608A3 (es) |
EE (1) | EE04565B1 (es) |
HK (1) | HK1042091A1 (es) |
HU (1) | HUP0202214A3 (es) |
IL (1) | IL145505A0 (es) |
IS (1) | IS6103A (es) |
MY (1) | MY122392A (es) |
NO (1) | NO321405B1 (es) |
NZ (1) | NZ514477A (es) |
PL (1) | PL350907A1 (es) |
RU (1) | RU2254333C2 (es) |
SA (1) | SA00210124B1 (es) |
SK (1) | SK13422001A3 (es) |
TR (1) | TR200102911T2 (es) |
WO (1) | WO2000061569A1 (es) |
Families Citing this family (68)
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SE9902270D0 (sv) | 1999-06-16 | 1999-06-16 | Astra Ab | Pharmaceutically active compounds |
SE9903759D0 (sv) | 1999-10-18 | 1999-10-18 | Astra Ab | Pharmaceutically active compounds |
SE9904505D0 (sv) * | 1999-12-09 | 1999-12-09 | Astra Pharma Prod | Novel compounds |
TWI258462B (en) | 1999-12-17 | 2006-07-21 | Astrazeneca Ab | Adamantane derivative compounds, process for preparing the same and pharmaceutical composition comprising the same |
SE9904738D0 (sv) * | 1999-12-22 | 1999-12-22 | Astra Pharma Prod | Novel compounds |
SE9904765D0 (sv) | 1999-12-23 | 1999-12-23 | Astra Ab | Pharmaceutically-useful compounds |
GB0013737D0 (en) | 2000-06-07 | 2000-07-26 | Astrazeneca Ab | Novel compounds |
US6808924B1 (en) | 2000-07-11 | 2004-10-26 | Claudia Lanari | Mouse mammary tumor lines expressing estrogen and progesterone receptors |
AR030756A1 (es) * | 2000-10-02 | 2003-09-03 | Astrazeneca Ab | Compuesto de oxabispidina util en el tratamiento de arritmias cardiacas |
JP2002330787A (ja) * | 2000-10-21 | 2002-11-19 | Astrazeneca Ab | 化学物質 |
US6833457B1 (en) * | 2001-01-18 | 2004-12-21 | Takeda Chemical Industries, Ltd. | Process for preparation of benzylpiperidine compounds |
TWI259836B (en) * | 2001-04-12 | 2006-08-11 | Astrazeneca Ab | Modified release formulation suitable for antiarrhythmic compounds |
SE0101329D0 (sv) * | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | Pharmaceutical formulation |
WO2003042190A1 (en) * | 2001-11-12 | 2003-05-22 | Pfizer Products Inc. | N-alkyl-adamantyl derivatives as p2x7-receptor antagonists |
PA8557501A1 (es) | 2001-11-12 | 2003-06-30 | Pfizer Prod Inc | Benzamida, heteroarilamida y amidas inversas |
SE0103836D0 (sv) | 2001-11-16 | 2001-11-16 | Astrazeneca Ab | Novel compounds |
SE0200920D0 (sv) * | 2002-03-25 | 2002-03-25 | Astrazeneca Ab | Novel compounds |
US7071223B1 (en) | 2002-12-31 | 2006-07-04 | Pfizer, Inc. | Benzamide inhibitors of the P2X7 receptor |
PA8591801A1 (es) * | 2002-12-31 | 2004-07-26 | Pfizer Prod Inc | Inhibidores benzamidicos del receptor p2x7. |
TWI336696B (en) * | 2003-01-27 | 2011-02-01 | Astellas Pharma Inc | Thiazole derivatives |
DE10306250A1 (de) * | 2003-02-14 | 2004-09-09 | Aventis Pharma Deutschland Gmbh | Substituierte N-Arylheterozyklen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
US7223788B2 (en) | 2003-02-14 | 2007-05-29 | Sanofi-Aventis Deutschland Gmbh | Substituted N-aryl heterocycles, process for their preparation and their use as medicaments |
SE0300445D0 (sv) * | 2003-02-18 | 2003-02-18 | Astrazeneca Ab | New combination |
SE0300480D0 (sv) * | 2003-02-21 | 2003-02-21 | Astrazeneca Ab | Novel compounds |
ES2396565T3 (es) * | 2003-05-12 | 2013-02-22 | Pah Usa 15 Llc | Inhibidores benzamida del receptor P2X7 |
WO2004105796A1 (en) * | 2003-05-29 | 2004-12-09 | Astrazeneca Ab | A pharmaceutical composition containing a p2x7 receptor antagonist and methotrexate |
EP1644041A1 (en) * | 2003-05-29 | 2006-04-12 | AstraZeneca AB | A pharmaceutical composition comprising a p2x7 antagonist and sulfasalazine |
JP2007501270A (ja) * | 2003-05-29 | 2007-01-25 | アストラゼネカ・アクチエボラーグ | P2X7受容体アンタゴニストおよび腫瘍壊死因子αを含む医薬組成物 |
GB0312609D0 (en) | 2003-06-02 | 2003-07-09 | Astrazeneca Ab | Novel compounds |
GB0324498D0 (en) | 2003-07-21 | 2003-11-26 | Aventis Pharma Inc | Heterocyclic compounds as P2X7 ion channel blockers |
SE0302192D0 (sv) * | 2003-08-08 | 2003-08-08 | Astrazeneca Ab | Novel compounds |
SE0302488D0 (sv) * | 2003-09-18 | 2003-09-18 | Astrazeneca Ab | New combination |
SE0401539D0 (sv) | 2004-06-15 | 2004-06-15 | Astrazeneca Ab | New compounds |
BRPI0512915A (pt) * | 2004-06-29 | 2008-04-15 | Warner Lambert Co | terapias de combinação utilizando inibidores benzamida do receptor p2x7 |
CA2572118A1 (en) * | 2004-06-29 | 2006-01-12 | Pfizer Products Inc. | Method for preparing 5-`4-(2-hydroxy-ethyl)-3,5-dioxo-4,5-dihydro-3h-`1,2,4!-triazin-2-yl!benzamide derivatives with p2x7 inhibiting activity by reaction of the derivative unsubstituted in 4-position of the triazine with an oxiran in the presence of a lewis acid |
MXPA06014022A (es) * | 2004-06-29 | 2007-02-08 | Pfizer Prod Inc | Prcedimientos para preparar inhibidores de p2x7. |
SA05260265A (ar) * | 2004-08-30 | 2005-12-03 | استرازينيكا ايه بي | مركبات جديدة |
SE0402925D0 (sv) * | 2004-11-30 | 2004-11-30 | Astrazeneca Ab | Novel Compounds |
MX2007015800A (es) | 2005-06-13 | 2008-03-04 | Astrazeneca Ab | Compuestos de oxabispidina novedosos para el tratamiento de arritmias cardiacas. |
WO2007008157A1 (en) * | 2005-07-11 | 2007-01-18 | Astrazeneca Ab | New combination 2 |
WO2007008155A1 (en) * | 2005-07-11 | 2007-01-18 | Astrazeneca Ab | New combination 1 |
US20090036429A1 (en) * | 2006-02-17 | 2009-02-05 | Ohler Norman E | Hydroxypiperidine Derivatives and Uses Thereof |
WO2008083124A1 (en) | 2006-12-28 | 2008-07-10 | Rigel Pharmaceuticals, Inc. | N-substituted-heterocycloalkyloxybenzamide compounds and methods of use |
KR20090122396A (ko) | 2007-03-22 | 2009-11-27 | 아스트라제네카 아베 | 염증성 질환 치료용 퀴놀린 유도체 |
JP2010535816A (ja) * | 2007-08-10 | 2010-11-25 | ハー・ルンドベック・アクチエゼルスカベット | ヘテロアリールアミド類似体 |
US8106073B2 (en) | 2007-11-30 | 2012-01-31 | Astrazeneca Ab | Quinoline derivatives 057 |
EA022505B1 (ru) | 2008-03-25 | 2016-01-29 | Эффектис Фармасьютиклз Аг | Новые p2x7r антагонисты и их применение |
PT2243772E (pt) | 2009-04-14 | 2012-03-28 | Affectis Pharmaceuticals Ag | Novos antagonistas de p2x7r e sua utilização |
EP2322149A1 (en) | 2009-11-03 | 2011-05-18 | Universidad del Pais Vasco | Methods and compositions for the treatment of ischemia |
EA201201548A1 (ru) | 2010-05-14 | 2013-05-30 | Эффектис Фармасьютиклз Аг | Новые способы получения p2x7r антагонистов |
WO2012110190A1 (en) | 2011-02-17 | 2012-08-23 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
EP2678317A1 (en) * | 2011-02-22 | 2014-01-01 | Actelion Pharmaceuticals Ltd. | Benzamide derivatives as p2x7 receptor antagonists |
WO2012163456A1 (en) | 2011-05-27 | 2012-12-06 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
WO2012163792A1 (en) | 2011-05-27 | 2012-12-06 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
US9221832B2 (en) | 2011-07-22 | 2015-12-29 | Actelion Pharmaceuticals Ltd. | Heterocyclic amide derivatives as P2X7 receptor antagonists |
TWI576347B (zh) | 2012-01-20 | 2017-04-01 | 艾克泰聯製藥有限公司 | 作為p2x受體拮抗劑之雜環醯胺衍生物 |
UA110336C2 (uk) | 2012-10-05 | 2015-12-25 | Hlib Volodymyrovych Zagorii | Фармацевтична композиція 1-адамантилетилокси-3-морфоліно-2-пропанолу або його фармацевтично прийнятних солей як кардіопротекторний лікарський засіб |
PL2931717T3 (pl) | 2012-12-12 | 2017-05-31 | Actelion Pharmaceuticals Ltd. | Pochodne indolokarboksyamidu jako antagoniści receptora p2x7 |
KR102232744B1 (ko) | 2012-12-18 | 2021-03-26 | 이도르시아 파마슈티컬스 리미티드 | P2x7 수용체 길항제로서의 인돌 카르복사미드 유도체 |
CA2897459C (en) | 2013-01-22 | 2021-03-02 | Actelion Pharmaceuticals Ltd | Heterocyclic amide derivatives as p2x7 receptor antagonists |
WO2014115072A1 (en) | 2013-01-22 | 2014-07-31 | Actelion Pharmaceuticals Ltd | Heterocyclic amide derivatives as p2x7 receptor antagonists |
CN103304502B (zh) * | 2013-06-02 | 2015-03-04 | 张远强 | 一类抗糖尿病化合物、其制备方法和用途 |
CN103304498B (zh) * | 2013-06-02 | 2015-03-04 | 张远强 | 一种抗糖尿病化合物、其制备方法和用途 |
CN103304500B (zh) * | 2013-06-02 | 2015-03-04 | 张远强 | 新型抗糖尿病化合物、其制备方法和用途 |
CN103304503B (zh) * | 2013-06-02 | 2015-03-04 | 张远强 | 抗糖尿病化合物、其制备方法和用途 |
US10548877B2 (en) | 2016-03-11 | 2020-02-04 | Takeda Pharmaceutical Company Limited | Aromatic ring compound |
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Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
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US3464998A (en) | 1968-03-04 | 1969-09-02 | Searle & Co | Adamantyl esters and amides of pyridinecarboxylic acids |
US3789072A (en) * | 1970-04-22 | 1974-01-29 | Squibb & Sons Inc | Carboxamides |
CA2015473C (en) * | 1989-04-28 | 1998-04-14 | Iwao Kinoshita | Triphenylmethane derivatives |
DE69426205T2 (de) | 1993-08-10 | 2001-03-08 | James Black Foundation Ltd., London | Gastrin-und cck-rezeptorligande |
DE19608653A1 (de) | 1996-03-06 | 1997-09-11 | Thomae Gmbh Dr K | Pyrimido[5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
SE9704545D0 (sv) * | 1997-12-05 | 1997-12-05 | Astra Pharma Prod | Novel compounds |
SE9704544D0 (sv) * | 1997-12-05 | 1997-12-05 | Astra Pharma Prod | Novel compounds |
-
2000
- 2000-04-06 AU AU39947/00A patent/AU774526B2/en not_active Ceased
- 2000-04-06 CA CA002368829A patent/CA2368829A1/en not_active Abandoned
- 2000-04-06 IL IL14550500A patent/IL145505A0/xx unknown
- 2000-04-06 HU HU0202214A patent/HUP0202214A3/hu unknown
- 2000-04-06 BR BR0009651-2A patent/BR0009651A/pt not_active IP Right Cessation
- 2000-04-06 KR KR1020017012826A patent/KR100710091B1/ko not_active IP Right Cessation
- 2000-04-06 EP EP00919245A patent/EP1171432A1/en not_active Withdrawn
- 2000-04-06 NZ NZ514477A patent/NZ514477A/xx unknown
- 2000-04-06 CZ CZ20013608A patent/CZ20013608A3/cs unknown
- 2000-04-06 JP JP2000610843A patent/JP2002541249A/ja not_active Withdrawn
- 2000-04-06 TR TR2001/02911T patent/TR200102911T2/xx unknown
- 2000-04-06 SK SK1342-2001A patent/SK13422001A3/sk unknown
- 2000-04-06 WO PCT/SE2000/000663 patent/WO2000061569A1/en active Search and Examination
- 2000-04-06 CN CNB008084424A patent/CN1147483C/zh not_active Expired - Fee Related
- 2000-04-06 EE EEP200100525A patent/EE04565B1/xx not_active IP Right Cessation
- 2000-04-06 RU RU2001130140/04A patent/RU2254333C2/ru not_active IP Right Cessation
- 2000-04-06 PL PL00350907A patent/PL350907A1/xx not_active Application Discontinuation
- 2000-04-06 US US09/555,489 patent/US6492355B1/en not_active Expired - Fee Related
- 2000-04-07 AR ARP000101616A patent/AR023423A1/es not_active Application Discontinuation
- 2000-04-07 MY MYPI20001445A patent/MY122392A/en unknown
- 2000-05-28 SA SA00210124A patent/SA00210124B1/ar unknown
-
2001
- 2001-10-05 IS IS6103A patent/IS6103A/is unknown
- 2001-10-08 NO NO20014894A patent/NO321405B1/no unknown
-
2002
- 2002-05-27 HK HK02103932.3A patent/HK1042091A1/zh unknown
Also Published As
Publication number | Publication date |
---|---|
HK1042091A1 (zh) | 2002-08-02 |
NO20014894L (no) | 2001-12-10 |
CZ20013608A3 (cs) | 2002-05-15 |
TR200102911T2 (tr) | 2002-01-21 |
HUP0202214A2 (en) | 2002-10-28 |
KR20010108473A (ko) | 2001-12-07 |
BR0009651A (pt) | 2002-01-08 |
EE04565B1 (et) | 2005-12-15 |
SA00210124B1 (ar) | 2006-11-28 |
AU774526B2 (en) | 2004-07-01 |
KR100710091B1 (ko) | 2007-04-25 |
JP2002541249A (ja) | 2002-12-03 |
HUP0202214A3 (en) | 2002-12-28 |
EP1171432A1 (en) | 2002-01-16 |
WO2000061569A1 (en) | 2000-10-19 |
CA2368829A1 (en) | 2000-10-19 |
MY122392A (en) | 2006-04-29 |
AU3994700A (en) | 2000-11-14 |
EE200100525A (et) | 2002-12-16 |
IS6103A (is) | 2001-10-05 |
AR023423A1 (es) | 2002-09-04 |
CN1147483C (zh) | 2004-04-28 |
RU2254333C2 (ru) | 2005-06-20 |
CN1353702A (zh) | 2002-06-12 |
SK13422001A3 (sk) | 2002-05-09 |
US6492355B1 (en) | 2002-12-10 |
NZ514477A (en) | 2003-04-29 |
NO20014894D0 (no) | 2001-10-08 |
PL350907A1 (en) | 2003-02-10 |
IL145505A0 (en) | 2002-06-30 |
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