NO310189B1 - Substituerte oksimer, hydrazoner og olefiner, farmasöytiske preparater som omfatter disse, og anvendelse av forbindelsene tilfremstilling av medikamenter - Google Patents
Substituerte oksimer, hydrazoner og olefiner, farmasöytiske preparater som omfatter disse, og anvendelse av forbindelsene tilfremstilling av medikamenter Download PDFInfo
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- NO310189B1 NO310189B1 NO19975029A NO975029A NO310189B1 NO 310189 B1 NO310189 B1 NO 310189B1 NO 19975029 A NO19975029 A NO 19975029A NO 975029 A NO975029 A NO 975029A NO 310189 B1 NO310189 B1 NO 310189B1
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- Prior art keywords
- mmol
- product
- phenyl
- alkyl
- formula
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 218
- 239000003814 drug Substances 0.000 title claims description 9
- 150000001336 alkenes Chemical class 0.000 title abstract description 9
- 150000007857 hydrazones Chemical class 0.000 title abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 3
- 238000004519 manufacturing process Methods 0.000 title description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 38
- -1 N-substituted piperazinyl Chemical group 0.000 claims abstract description 31
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 9
- 206010006482 Bronchospasm Diseases 0.000 claims abstract description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 7
- 208000006673 asthma Diseases 0.000 claims abstract description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- 208000009079 Bronchial Spasm Diseases 0.000 claims abstract description 6
- 208000014181 Bronchial disease Diseases 0.000 claims abstract description 6
- 206010011224 Cough Diseases 0.000 claims abstract description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 5
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 4
- 125000005545 phthalimidyl group Chemical group 0.000 claims abstract description 3
- 238000002360 preparation method Methods 0.000 claims description 51
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 208000015114 central nervous system disease Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000002393 azetidinyl group Chemical group 0.000 claims description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 2
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 claims description 2
- 125000004193 piperazinyl group Chemical class 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims 1
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 1
- 208000025985 Central nervous system inflammatory disease Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 100
- 150000002923 oximes Chemical class 0.000 abstract description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 5
- 208000018522 Gastrointestinal disease Diseases 0.000 abstract description 4
- 125000003118 aryl group Chemical group 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Chemical class CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 abstract description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract description 2
- 201000010099 disease Diseases 0.000 abstract description 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract 2
- 101001109689 Homo sapiens Nuclear receptor subfamily 4 group A member 3 Proteins 0.000 abstract 1
- 101000598778 Homo sapiens Protein OSCP1 Proteins 0.000 abstract 1
- 101001067395 Mus musculus Phospholipid scramblase 1 Proteins 0.000 abstract 1
- 102100022673 Nuclear receptor subfamily 4 group A member 3 Human genes 0.000 abstract 1
- 125000002757 morpholinyl group Chemical group 0.000 abstract 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 220
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 204
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 200
- 239000000047 product Substances 0.000 description 196
- 239000000243 solution Substances 0.000 description 149
- 235000019439 ethyl acetate Nutrition 0.000 description 110
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 100
- 239000000203 mixture Substances 0.000 description 97
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 92
- 229910001868 water Inorganic materials 0.000 description 90
- 239000000460 chlorine Substances 0.000 description 89
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 76
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 75
- 239000002904 solvent Substances 0.000 description 65
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 64
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 63
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 52
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 52
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 51
- 238000006243 chemical reaction Methods 0.000 description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- 239000007787 solid Substances 0.000 description 48
- 229920006395 saturated elastomer Polymers 0.000 description 46
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- 239000012044 organic layer Substances 0.000 description 41
- 239000003480 eluent Substances 0.000 description 38
- 239000000741 silica gel Substances 0.000 description 37
- 229910002027 silica gel Inorganic materials 0.000 description 37
- 239000003921 oil Substances 0.000 description 36
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 35
- 239000011541 reaction mixture Substances 0.000 description 31
- 239000011734 sodium Substances 0.000 description 31
- 238000010898 silica gel chromatography Methods 0.000 description 29
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 28
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
- 150000001412 amines Chemical class 0.000 description 27
- 239000012043 crude product Substances 0.000 description 27
- 238000010992 reflux Methods 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- 239000002585 base Substances 0.000 description 26
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- 102100024304 Protachykinin-1 Human genes 0.000 description 23
- 239000010410 layer Substances 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 21
- 239000000284 extract Substances 0.000 description 21
- 230000002829 reductive effect Effects 0.000 description 21
- 108010040722 Neurokinin-2 Receptors Proteins 0.000 description 20
- 150000002576 ketones Chemical class 0.000 description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 19
- 239000006260 foam Substances 0.000 description 19
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 18
- 239000003960 organic solvent Substances 0.000 description 18
- 239000000725 suspension Substances 0.000 description 18
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 16
- 238000003756 stirring Methods 0.000 description 15
- 101800000399 Neurokinin A Proteins 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- 238000007792 addition Methods 0.000 description 13
- 239000012267 brine Substances 0.000 description 13
- 238000004587 chromatography analysis Methods 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- 239000007858 starting material Substances 0.000 description 13
- 238000004809 thin layer chromatography Methods 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
- 239000000377 silicon dioxide Substances 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- 150000001350 alkyl halides Chemical class 0.000 description 11
- 238000005292 vacuum distillation Methods 0.000 description 11
- 150000001299 aldehydes Chemical class 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 9
- 229910021529 ammonia Inorganic materials 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 239000012230 colorless oil Substances 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 9
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 8
- 229910004373 HOAc Inorganic materials 0.000 description 8
- 231100000673 dose–response relationship Toxicity 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 8
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 7
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
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- 229910052682 stishovite Inorganic materials 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 7
- 229910052905 tridymite Inorganic materials 0.000 description 7
- KQKFQBTWXOGINC-UHFFFAOYSA-N 4-phenylpiperidin-4-ol Chemical compound C=1C=CC=CC=1C1(O)CCNCC1 KQKFQBTWXOGINC-UHFFFAOYSA-N 0.000 description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- 239000003810 Jones reagent Substances 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- 239000013058 crude material Substances 0.000 description 6
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 6
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- 150000004820 halides Chemical class 0.000 description 6
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
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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
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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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
- C07D211/52—Oxygen atoms attached in position 4 having an aryl radical 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
- C07D211/06—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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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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- 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
- C07D211/72—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 hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- C—CHEMISTRY; METALLURGY
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- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
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- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US43274095A | 1995-05-02 | 1995-05-02 | |
US46081995A | 1995-06-01 | 1995-06-01 | |
PCT/US1996/005659 WO1996034857A1 (en) | 1995-05-02 | 1996-05-01 | Substituted oximes, hydrazones and olefins as neurokinin antagonists |
Publications (3)
Publication Number | Publication Date |
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NO975029D0 NO975029D0 (no) | 1997-10-31 |
NO975029L NO975029L (no) | 1997-12-30 |
NO310189B1 true NO310189B1 (no) | 2001-06-05 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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NO19975029A NO310189B1 (no) | 1995-05-02 | 1997-10-31 | Substituerte oksimer, hydrazoner og olefiner, farmasöytiske preparater som omfatter disse, og anvendelse av forbindelsene tilfremstilling av medikamenter |
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US (2) | US5696267A (de) |
EP (1) | EP0823896B1 (de) |
JP (1) | JP3255421B2 (de) |
KR (1) | KR100248921B1 (de) |
CN (1) | CN1134414C (de) |
AT (1) | ATE203014T1 (de) |
AU (1) | AU706526B2 (de) |
BR (1) | BR9608269A (de) |
CA (1) | CA2218913C (de) |
CZ (1) | CZ342497A3 (de) |
DE (1) | DE69613833T2 (de) |
DK (1) | DK0823896T3 (de) |
ES (1) | ES2158314T3 (de) |
GR (1) | GR3036676T3 (de) |
HK (1) | HK1008221A1 (de) |
HU (1) | HU222048B1 (de) |
MX (1) | MX9708415A (de) |
NO (1) | NO310189B1 (de) |
NZ (1) | NZ307715A (de) |
PL (1) | PL323088A1 (de) |
PT (1) | PT823896E (de) |
SK (1) | SK147197A3 (de) |
WO (1) | WO1996034857A1 (de) |
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US5688960A (en) * | 1995-05-02 | 1997-11-18 | Schering Corporation | Substituted oximes, hydrazones and olefins useful as neurokinin antagonists |
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US6265614B1 (en) | 1997-10-27 | 2001-07-24 | Schering Corporation | Optically active intermediates for the preparation of optically active substituted oximes, hydrazones and olefins useful as neurokinin antagonists |
CA2308073A1 (en) * | 1997-10-27 | 1999-05-06 | Schering Corporation | Optically active intermediates for the preparation of optically active substituted oximes, hydrazones and olefins useful as neurokinin antagonists |
IL135408A0 (en) * | 1997-11-21 | 2001-05-20 | Schering Corp | Substituted oximes as neurokinin antagonists |
ID29137A (id) * | 1998-07-27 | 2001-08-02 | Schering Corp | Ligan-ligan afinitas tinggi untuk reseptor nosiseptin orl-1 |
US6221880B1 (en) | 1998-10-09 | 2001-04-24 | Schering Corporation | Composition and method for treating allergic diseases |
US6103735A (en) * | 1998-10-09 | 2000-08-15 | Schering Corporation | Composition and method for treating allergic diseases |
US6063926A (en) * | 1998-11-18 | 2000-05-16 | Schering Corporation | Substituted oximes as neurokinin antagonists |
CA2355886C (en) * | 1998-12-23 | 2006-10-31 | Schering Corporation | Substituted oximes and hydrazones as neurokinin antagonists |
US6204265B1 (en) | 1998-12-23 | 2001-03-20 | Schering Corporation | Substituted oximes and hydrazones as neurokinin antagonists |
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GB0011838D0 (en) * | 2000-05-17 | 2000-07-05 | Astrazeneca Ab | Chemical compounds |
DE60129562T2 (de) * | 2000-06-12 | 2008-04-17 | The University Of Rochester | Methode zur Behandlung von Hitzewallungen durch Verwendung eines Tachykinin-Rezeptor-Antagonisten |
GB0104050D0 (en) * | 2001-02-19 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
GB0107228D0 (en) * | 2001-03-22 | 2001-05-16 | Astrazeneca Ab | Chemical compounds |
GB0108046D0 (en) * | 2001-03-30 | 2001-05-23 | Astrazeneca Ab | Chemical compounds |
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GB0120461D0 (en) | 2001-08-22 | 2001-10-17 | Astrazeneca Ab | Novel compounds |
PE20030703A1 (es) * | 2001-09-06 | 2003-08-21 | Schering Corp | Inhibidores de la 17b-hidroxiesteroide deshidrogenasa tipo 3 |
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WO2003100033A2 (en) | 2002-03-13 | 2003-12-04 | Biogen Idec Ma Inc. | ANTI-αvβ6 ANTIBODIES |
SE0200843D0 (sv) | 2002-03-19 | 2002-03-19 | Astrazeneca Ab | Chemical compounds |
SE0200844D0 (sv) | 2002-03-19 | 2002-03-19 | Astrazeneca Ab | Chemical compounds |
CA2507509A1 (en) * | 2002-11-25 | 2004-06-10 | Mochida Pharmaceutical Co., Ltd. | Therapeutic agent for respiratory disease containing 4-hydroxypiperidine derivative as active ingredient |
SE0300957D0 (sv) | 2003-04-01 | 2003-04-01 | Astrazeneca Ab | Chemical compounds |
SE0301369D0 (sv) * | 2003-05-09 | 2003-05-09 | Astrazeneca Ab | Chemical compounds |
TW200630337A (en) | 2004-10-14 | 2006-09-01 | Euro Celtique Sa | Piperidinyl compounds and the use thereof |
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FR2473518A1 (fr) * | 1980-01-16 | 1981-07-17 | Unicler | Derives du phenyl-1 morpholino-4 butene-1 ol-3, leur preparation et leur application en therapeutique |
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GB9408872D0 (en) * | 1994-05-03 | 1994-06-22 | Zeneca Ltd | Heterocyclic compounds |
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1996
- 1996-04-30 US US08/641,384 patent/US5696267A/en not_active Expired - Lifetime
- 1996-05-01 AU AU57140/96A patent/AU706526B2/en not_active Ceased
- 1996-05-01 KR KR1019970707757A patent/KR100248921B1/ko not_active IP Right Cessation
- 1996-05-01 CN CNB961951729A patent/CN1134414C/zh not_active Expired - Fee Related
- 1996-05-01 JP JP53335496A patent/JP3255421B2/ja not_active Expired - Fee Related
- 1996-05-01 BR BR9608269A patent/BR9608269A/pt not_active Application Discontinuation
- 1996-05-01 NZ NZ307715A patent/NZ307715A/xx unknown
- 1996-05-01 PT PT96915341T patent/PT823896E/pt unknown
- 1996-05-01 EP EP96915341A patent/EP0823896B1/de not_active Expired - Lifetime
- 1996-05-01 HU HU9800840A patent/HU222048B1/hu not_active IP Right Cessation
- 1996-05-01 SK SK1471-97A patent/SK147197A3/sk unknown
- 1996-05-01 MX MX9708415A patent/MX9708415A/es not_active IP Right Cessation
- 1996-05-01 WO PCT/US1996/005659 patent/WO1996034857A1/en not_active Application Discontinuation
- 1996-05-01 ES ES96915341T patent/ES2158314T3/es not_active Expired - Lifetime
- 1996-05-01 CA CA002218913A patent/CA2218913C/en not_active Expired - Fee Related
- 1996-05-01 PL PL96323088A patent/PL323088A1/xx unknown
- 1996-05-01 AT AT96915341T patent/ATE203014T1/de not_active IP Right Cessation
- 1996-05-01 DE DE69613833T patent/DE69613833T2/de not_active Expired - Lifetime
- 1996-05-01 DK DK96915341T patent/DK0823896T3/da active
- 1996-05-01 CZ CZ973424A patent/CZ342497A3/cs unknown
-
1997
- 1997-07-25 US US08/901,028 patent/US5840725A/en not_active Expired - Lifetime
- 1997-10-31 NO NO19975029A patent/NO310189B1/no not_active IP Right Cessation
-
1998
- 1998-07-17 HK HK98109217A patent/HK1008221A1/xx not_active IP Right Cessation
-
2001
- 2001-09-20 GR GR20010401533T patent/GR3036676T3/el not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
ES2158314T3 (es) | 2001-09-01 |
ATE203014T1 (de) | 2001-07-15 |
US5696267A (en) | 1997-12-09 |
DE69613833D1 (de) | 2001-08-16 |
HU222048B1 (hu) | 2003-04-28 |
HK1008221A1 (en) | 1999-05-07 |
JPH10506923A (ja) | 1998-07-07 |
CN1189821A (zh) | 1998-08-05 |
MX9708415A (es) | 1998-02-28 |
SK147197A3 (en) | 1998-08-05 |
NO975029L (no) | 1997-12-30 |
WO1996034857A1 (en) | 1996-11-07 |
EP0823896B1 (de) | 2001-07-11 |
AU5714096A (en) | 1996-11-21 |
GR3036676T3 (en) | 2001-12-31 |
HUP9800840A2 (hu) | 1998-08-28 |
NO975029D0 (no) | 1997-10-31 |
EP0823896A1 (de) | 1998-02-18 |
CA2218913A1 (en) | 1996-11-07 |
HUP9800840A3 (en) | 1998-09-28 |
CA2218913C (en) | 2003-03-04 |
KR19990008231A (ko) | 1999-01-25 |
KR100248921B1 (ko) | 2000-04-01 |
DE69613833T2 (de) | 2002-04-04 |
PT823896E (pt) | 2001-11-30 |
US5840725A (en) | 1998-11-24 |
DK0823896T3 (da) | 2001-09-24 |
BR9608269A (pt) | 1999-02-17 |
PL323088A1 (en) | 1998-03-02 |
CZ342497A3 (cs) | 1998-07-15 |
JP3255421B2 (ja) | 2002-02-12 |
AU706526B2 (en) | 1999-06-17 |
NZ307715A (en) | 2000-01-28 |
CN1134414C (zh) | 2004-01-14 |
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