NO319542B1 - Tricykliske triazolbenzazepinderivater, fremgangsmate til fremstilling derav, samt antiallergiske midler - Google Patents

Tricykliske triazolbenzazepinderivater, fremgangsmate til fremstilling derav, samt antiallergiske midler Download PDF

Info

Publication number: NO319542B1
Authority: NO; Norway
Prior art keywords: triazole; formula; compound; ethylcarboxylate; prepared
Prior art date: 1997-09-29

Application number

NO20001500A

Other languages

English (en)

Norwegian (no)

Other versions

NO20001500D0 (no

NO20001500L (no

Inventor

Mami Kawaguchi

Yumiko Okada

Yasuo Ohtsuka

Toshio Nishizuka

Sohjiro Shiokawa

Seiji Tsutsumi

Hideo Kitagawa

Hiromi Takata

Takashi Shishikura

Toyoaki Ishikura

Kenichi Fushihara

Sachiko Miyamoto

Maki Shiobara

Original Assignee

Meiji Seika Kaisha

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-09-29

Filing date

2000-03-23

Publication date

2005-08-29

2000-03-23 Application filed by Meiji Seika Kaisha filed Critical Meiji Seika Kaisha

2000-03-23 Publication of NO20001500D0 publication Critical patent/NO20001500D0/no

2000-05-18 Publication of NO20001500L publication Critical patent/NO20001500L/no

2005-08-29 Publication of NO319542B1 publication Critical patent/NO319542B1/no

Links

-1 triazole benzazepine derivatives Chemical class 0.000 title claims description 57
239000000043 antiallergic agent Substances 0.000 title abstract description 4
238000002360 preparation method Methods 0.000 title description 55
238000000034 method Methods 0.000 title description 45
230000008569 process Effects 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 236
150000003839 salts Chemical class 0.000 claims abstract description 29
239000012453 solvate Substances 0.000 claims abstract description 22
125000000217 alkyl group Chemical group 0.000 claims abstract description 9
239000003814 drug Substances 0.000 claims description 14
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
238000011282 treatment Methods 0.000 claims description 9
125000006239 protecting group Chemical group 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
208000026935 allergic disease Diseases 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
239000000825 pharmaceutical preparation Substances 0.000 claims description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
229940124597 therapeutic agent Drugs 0.000 claims description 4
125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 3
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
125000001425 triazolyl group Chemical group 0.000 claims 1
125000003545 alkoxy group Chemical group 0.000 abstract description 9
239000001257 hydrogen Substances 0.000 abstract description 6
229910052739 hydrogen Inorganic materials 0.000 abstract description 6
239000000651 prodrug Substances 0.000 abstract description 6
229940002612 prodrug Drugs 0.000 abstract description 6
QDEVEJYEXBFIJD-UHFFFAOYSA-N triazolo[4,5-i][1]benzazepine Chemical class C1=CC2=CC=CC=NC2=C2C1=NN=N2 QDEVEJYEXBFIJD-UHFFFAOYSA-N 0.000 abstract description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 3
125000003342 alkenyl group Chemical group 0.000 abstract description 2
229910052736 halogen Inorganic materials 0.000 abstract 2
150000002367 halogens Chemical class 0.000 abstract 2
150000002431 hydrogen Chemical class 0.000 abstract 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 abstract 1
125000003884 phenylalkyl group Chemical group 0.000 abstract 1
125000000547 substituted alkyl group Chemical group 0.000 abstract 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 170
238000005160 1H NMR spectroscopy Methods 0.000 description 130
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 114
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 114
239000000243 solution Substances 0.000 description 101
239000000203 mixture Substances 0.000 description 99
238000006243 chemical reaction Methods 0.000 description 65
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 60
238000002451 electron ionisation mass spectrometry Methods 0.000 description 60
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 47
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
239000000843 powder Substances 0.000 description 41
239000002904 solvent Substances 0.000 description 40
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
239000003921 oil Substances 0.000 description 35
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 33
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
239000000543 intermediate Substances 0.000 description 24
230000002829 reductive effect Effects 0.000 description 24
239000000741 silica gel Substances 0.000 description 24
229910002027 silica gel Inorganic materials 0.000 description 24
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
238000004440 column chromatography Methods 0.000 description 23
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 18
239000012044 organic layer Substances 0.000 description 18
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 18
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 18
239000006260 foam Substances 0.000 description 17
QHOINBKBMJLHPY-UHFFFAOYSA-N 2-chloroethyl formate Chemical compound ClCCOC=O QHOINBKBMJLHPY-UHFFFAOYSA-N 0.000 description 16
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
239000012300 argon atmosphere Substances 0.000 description 15
238000000926 separation method Methods 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 14
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 14
229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
235000017557 sodium bicarbonate Nutrition 0.000 description 14
238000007796 conventional method Methods 0.000 description 13
239000012043 crude product Substances 0.000 description 13
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 13
238000000746 purification Methods 0.000 description 13
150000003852 triazoles Chemical class 0.000 description 13
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 11
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
239000000047 product Substances 0.000 description 11
229920006395 saturated elastomer Polymers 0.000 description 11
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
229940079593 drug Drugs 0.000 description 10
238000003756 stirring Methods 0.000 description 10
125000001424 substituent group Chemical group 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
238000001816 cooling Methods 0.000 description 8
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 8
238000006396 nitration reaction Methods 0.000 description 8
229910000027 potassium carbonate Inorganic materials 0.000 description 8
235000011181 potassium carbonates Nutrition 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
229930040373 Paraformaldehyde Natural products 0.000 description 7
ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 7
229920002866 paraformaldehyde Polymers 0.000 description 7
239000000725 suspension Substances 0.000 description 7
IAKGGJYLHBHSQD-UHFFFAOYSA-N 1-(azidomethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CN=[N+]=[N-])C=C1 IAKGGJYLHBHSQD-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
230000003111 delayed effect Effects 0.000 description 6
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
238000001914 filtration Methods 0.000 description 6
239000008187 granular material Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
238000006722 reduction reaction Methods 0.000 description 6
235000009518 sodium iodide Nutrition 0.000 description 6
238000001228 spectrum Methods 0.000 description 6
229910052794 bromium Inorganic materials 0.000 description 5
125000005843 halogen group Chemical group 0.000 description 5
125000000623 heterocyclic group Chemical group 0.000 description 5
239000013067 intermediate product Substances 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
230000009467 reduction Effects 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
239000003826 tablet Substances 0.000 description 5
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
229920002134 Carboxymethyl cellulose Polymers 0.000 description 4
206010020751 Hypersensitivity Diseases 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical group [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
239000002585 base Substances 0.000 description 4
KPWJBEFBFLRCLH-UHFFFAOYSA-L cadmium bromide Chemical group Br[Cd]Br KPWJBEFBFLRCLH-UHFFFAOYSA-L 0.000 description 4
OKIIEJOIXGHUKX-UHFFFAOYSA-L cadmium iodide Chemical group [Cd+2].[I-].[I-] OKIIEJOIXGHUKX-UHFFFAOYSA-L 0.000 description 4
235000010948 carboxy methyl cellulose Nutrition 0.000 description 4
229950008138 carmellose Drugs 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
239000013078 crystal Substances 0.000 description 4
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
239000011734 sodium Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical group Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 4
UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical group I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 4
BAHZSEFJKZYXRU-UHFFFAOYSA-N 2-chloropropan-2-yl formate Chemical compound C(=O)OC(C)(C)Cl BAHZSEFJKZYXRU-UHFFFAOYSA-N 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
229910001516 alkali metal iodide Inorganic materials 0.000 description 3
208000030961 allergic reaction Diseases 0.000 description 3
230000003266 anti-allergic effect Effects 0.000 description 3
208000006673 asthma Diseases 0.000 description 3
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
229910000024 caesium carbonate Inorganic materials 0.000 description 3
239000011575 calcium Substances 0.000 description 3
229910052791 calcium Inorganic materials 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
238000010511 deprotection reaction Methods 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
239000001863 hydroxypropyl cellulose Substances 0.000 description 3
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
150000007529 inorganic bases Chemical class 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000010410 layer Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
229910052751 metal Inorganic materials 0.000 description 3
239000002184 metal Substances 0.000 description 3
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
238000002156 mixing Methods 0.000 description 3
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 3
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 3
238000007363 ring formation reaction Methods 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
238000000638 solvent extraction Methods 0.000 description 3
238000004809 thin layer chromatography Methods 0.000 description 3
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
238000005406 washing Methods 0.000 description 3
WIHIUTUAHOZVLE-UHFFFAOYSA-N 1,3-diethoxypropan-2-ol Chemical compound CCOCC(O)COCC WIHIUTUAHOZVLE-UHFFFAOYSA-N 0.000 description 2
XZVBIIRIWFZJOE-UHFFFAOYSA-N 1-iodoethyl propan-2-yl carbonate Chemical compound CC(C)OC(=O)OC(C)I XZVBIIRIWFZJOE-UHFFFAOYSA-N 0.000 description 2
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
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239000006071 cream Substances 0.000 description 1
229960000265 cromoglicic acid Drugs 0.000 description 1
RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 1
125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000013461 design Methods 0.000 description 1
150000007654 dibenzocycloheptanes Chemical class 0.000 description 1
LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
NQGIJDNPUZEBRU-UHFFFAOYSA-N dodecanoyl chloride Chemical compound CCCCCCCCCCCC(Cl)=O NQGIJDNPUZEBRU-UHFFFAOYSA-N 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000010828 elution Methods 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
KLKFAASOGCDTDT-UHFFFAOYSA-N ethoxymethoxyethane Chemical compound CCOCOCC KLKFAASOGCDTDT-UHFFFAOYSA-N 0.000 description 1
HKKZLDQMWRNXOW-UHFFFAOYSA-N ethyl 5-[(4,5-dimethoxy-2-nitrophenyl)-hydroxymethyl]-1-[(4-methoxyphenyl)methyl]triazole-4-carboxylate Chemical compound C=1C(OC)=C(OC)C=C([N+]([O-])=O)C=1C(O)C1=C(C(=O)OCC)N=NN1CC1=CC=C(OC)C=C1 HKKZLDQMWRNXOW-UHFFFAOYSA-N 0.000 description 1
MTHCWXYWVMATGV-UHFFFAOYSA-N ethyl 5-[(4,5-dimethoxy-2-nitrophenyl)-hydroxymethyl]-3-[(4-methoxyphenyl)methyl]triazole-4-carboxylate Chemical compound CCOC(=O)C1=C(C(O)C=2C(=CC(OC)=C(OC)C=2)[N+]([O-])=O)N=NN1CC1=CC=C(OC)C=C1 MTHCWXYWVMATGV-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000003889 eye drop Substances 0.000 description 1
229940012356 eye drops Drugs 0.000 description 1
238000000434 field desorption mass spectrometry Methods 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
238000003304 gavage Methods 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
ARBOVOVUTSQWSS-UHFFFAOYSA-N hexadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCC(Cl)=O ARBOVOVUTSQWSS-UHFFFAOYSA-N 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
230000008105 immune reaction Effects 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
238000006317 isomerization reaction Methods 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
210000004400 mucous membrane Anatomy 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
239000007923 nasal drop Substances 0.000 description 1
229940100662 nasal drops Drugs 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
230000000802 nitrating effect Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002674 ointment Substances 0.000 description 1
229940126701 oral medication Drugs 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002902 organometallic compounds Chemical class 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229960003975 potassium Drugs 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
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
239000010936 titanium Substances 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical class OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- 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
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Pulmonology (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Molecular Biology (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Biochemistry (AREA)
Immunology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

NO20001500A 1997-09-29 2000-03-23 Tricykliske triazolbenzazepinderivater, fremgangsmate til fremstilling derav, samt antiallergiske midler NO319542B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
JP26461197		1997-09-29
JP5206398		1998-03-04
PCT/JP1998/004363 WO1999016770A1 (fr)	1997-09-29	1998-09-29	Derives de triazolobenzazepine tricyclique, leur procede de production et antiallergique

Publications (3)

Publication Number	Publication Date
NO20001500D0 NO20001500D0 (no)	2000-03-23
NO20001500L NO20001500L (no)	2000-05-18
NO319542B1 true NO319542B1 (no)	2005-08-29

Family

ID=26392670

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
NO20001500A NO319542B1 (no)	1997-09-29	2000-03-23	Tricykliske triazolbenzazepinderivater, fremgangsmate til fremstilling derav, samt antiallergiske midler
NO20043765A NO20043765L (no)	1997-09-29	2004-09-08	Tricykliske triazolbenzazepinderivater, fremgangsmate til fremstilling derav, samt antiallergiske midler

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
NO20043765A NO20043765L (no)	1997-09-29	2004-09-08	Tricykliske triazolbenzazepinderivater, fremgangsmate til fremstilling derav, samt antiallergiske midler

Country Status (24)

Country	Link
US (3)	US6372735B1 (fr)
EP (1)	EP1026167B1 (fr)
JP (1)	JP3188482B2 (fr)
KR (1)	KR100389140B1 (fr)
CN (2)	CN1155599C (fr)
AT (1)	ATE233764T1 (fr)
AU (1)	AU744636B2 (fr)
BR (1)	BR9814055B1 (fr)
CA (1)	CA2305307C (fr)
DE (1)	DE69811930T2 (fr)
DK (1)	DK1026167T3 (fr)
ES (1)	ES2191963T3 (fr)
HU (1)	HUP0004020A3 (fr)
ID (1)	ID24101A (fr)
IL (1)	IL135303A0 (fr)
NO (2)	NO319542B1 (fr)
NZ (1)	NZ503601A (fr)
PL (1)	PL339544A1 (fr)
PT (1)	PT1026167E (fr)
RU (1)	RU2198885C2 (fr)
SK (1)	SK283869B6 (fr)
TR (1)	TR200000808T2 (fr)
TW (1)	TW510902B (fr)
WO (1)	WO1999016770A1 (fr)

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ATE469902T1 (de) *	2001-12-26	2010-06-15	Meiji Seika Kaisha	Amorphe substanz eines tricyclischen triazolobenzazepinderivats
ES2283781T3 (es) *	2002-02-01	2007-11-01	Meiji Seika Kaisha, Ltd.	Procedimiento para producir un compuesto de 1,2,3-triazol.
AU2003259131A1 (en)	2002-07-09	2004-01-23	Bristol-Myers Squibb Company	Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method
BR0312503A (pt)	2002-07-09	2007-06-26	Bristol Myers Squibb Co	derivados heterocìclicos substituìdos úteis como agentes antidiabéticos e antiobesidade, composição farmacêutica, uso e combinação dos mesmos
WO2004113343A1 (fr) *	2003-06-19	2004-12-29	Meiji Seika Kaisha, Ltd.	Derive triazolobenzazepine tricyclique produit sous forme de nouvelle substance cristalline
EP1650266A1 (fr) *	2003-06-20	2006-04-26	Meiji Seika Kaisha Ltd.	Produit de coprecipitation d'une substance peu soluble et d'un polymere soluble dans l'eau, et procede de production de celui-ci
AU2005243175B2 (en)	2004-05-14	2011-12-01	Millennium Pharmaceuticals, Inc.	Compounds and methods for inhibiting mitotic progression by inhibition of Aurora kinase
US7910575B2 (en) *	2006-03-02	2011-03-22	Meiji Seika Kaisha, Ltd.	Prophylactic or therapeutic agents for allergic ophthalmic diseases or allergic nasal diseases, comprising tricyclic triazolobenzazepine derivative
EP2094711B8 (fr) *	2006-09-25	2018-03-28	Forschungsverbund Berlin e.V.	Structures mimétiques de peptides riches en proline, et leur utilisation pharmaceutique
CL2007003244A1 (es)	2006-11-16	2008-04-04	Millennium Pharm Inc	Compuestos derivados de pirimido[5,4-d][2]benzazepina; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento del cancer.
PT2123277E (pt) *	2007-12-18	2011-04-20	Meiji Seika Kaisha	Agente preventivo ou terapêutico para doenças inflamatórias do intestino
RU2535032C2 (ru)	2008-12-22	2014-12-10	Милленниум Фармасьютикалз, Инк.	Сочетание ингибиторов аврора киназы и анти-cd 20 антител
JO3635B1 (ar)	2009-05-18	2020-08-27	Millennium Pharm Inc	مركبات صيدلانية صلبة وطرق لانتاجها
EP2521545B1 (fr) *	2010-01-07	2019-11-27	Alkermes Pharma Ireland Limited	Promédicaments de composés hétéroaromatiques
BR112012020557A8 (pt)	2010-02-19	2018-01-02	Millennium Pharm Inc	formas cristalinas de 4-{[9-cloro-7-(2-flúor-6-metoifenil)-5h-pirimido[5,4-d][2]benzazepin-2-il]amino}-2-metoxibenzoato de sódio
US20130303519A1 (en)	2012-03-20	2013-11-14	Millennium Pharmaceuticals, Inc.	Methods of treating cancer using aurora kinase inhibitors
WO2014153509A1 (fr)	2013-03-22	2014-09-25	Millennium Pharmaceuticals, Inc.	Combinaison d'inhibiteurs catalytiques de mtorc1/2 et inhibiteurs sélectifs de la kinase aurora a
WO2017015316A1 (fr)	2015-07-21	2017-01-26	Millennium Pharmaceuticals, Inc.	Administration d'inhibiteur de kinase aurora et d'agents chimiothérapeutiques
BR112020013073A2 (pt) *	2017-12-29	2020-12-01	Biomarin Pharmaceutical Inc.	composto, composto, estereoisômero único ou mistura de estereoisômeros ou sal farmaceuticamente aceitável, composição farmacêutica, método de tratamento de uma doença ou distúrbio e composto ou sal farmaceuticamente aceitável do mesmo

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DE69411243T2 (de)	1993-04-16	1998-11-19	Shionogi & Co	Verfahren zur herstellung eines lignan-derivats
DE69427023T2 (de)	1993-12-28	2001-10-31	Meiji Seika K.K., Tokio/Tokyo	Tricyclische benzazepin-und benzothiazepin derivate
JP3537446B2 (ja) *	1995-06-15	2004-06-14	明治製菓株式会社	三環性ベンゾアゼピン化合物
EP0888350A1 (fr) *	1996-03-08	1999-01-07	Zeneca Limited	Principes actifs neurologiques derives d'azolobenzazepine
US20070059533A1 (en) *	2005-09-12	2007-03-15	Burdette Steven R	Thermal reflow of glass and fused silica body

1998
- 1998-09-29 ES ES98944289T patent/ES2191963T3/es not_active Expired - Lifetime
- 1998-09-29 AU AU91869/98A patent/AU744636B2/en not_active Ceased
- 1998-09-29 DK DK98944289T patent/DK1026167T3/da active
- 1998-09-29 TW TW087116198A patent/TW510902B/zh not_active IP Right Cessation
- 1998-09-29 CA CA002305307A patent/CA2305307C/fr not_active Expired - Fee Related
- 1998-09-29 TR TR2000/00808T patent/TR200000808T2/xx unknown
- 1998-09-29 IL IL13530398A patent/IL135303A0/xx unknown
- 1998-09-29 NZ NZ503601A patent/NZ503601A/en unknown
- 1998-09-29 BR BRPI9814055-8A patent/BR9814055B1/pt not_active IP Right Cessation
- 1998-09-29 CN CNB98810735XA patent/CN1155599C/zh not_active Expired - Fee Related
- 1998-09-29 HU HU0004020A patent/HUP0004020A3/hu unknown
- 1998-09-29 US US09/509,494 patent/US6372735B1/en not_active Expired - Lifetime
- 1998-09-29 JP JP51996999A patent/JP3188482B2/ja not_active Expired - Fee Related
- 1998-09-29 SK SK425-2000A patent/SK283869B6/sk unknown
- 1998-09-29 EP EP98944289A patent/EP1026167B1/fr not_active Expired - Lifetime
- 1998-09-29 PT PT98944289T patent/PT1026167E/pt unknown
- 1998-09-29 PL PL98339544A patent/PL339544A1/xx unknown
- 1998-09-29 AT AT98944289T patent/ATE233764T1/de active
- 1998-09-29 ID IDW20000808A patent/ID24101A/id unknown
- 1998-09-29 WO PCT/JP1998/004363 patent/WO1999016770A1/fr not_active Ceased
- 1998-09-29 DE DE69811930T patent/DE69811930T2/de not_active Expired - Lifetime
- 1998-09-29 KR KR10-2000-7003362A patent/KR100389140B1/ko not_active Expired - Fee Related
- 1998-09-29 CN CNB2003101047539A patent/CN1312135C/zh not_active Expired - Fee Related
- 1998-09-29 RU RU2000111517/04A patent/RU2198885C2/ru not_active IP Right Cessation
2000
- 2000-03-23 NO NO20001500A patent/NO319542B1/no unknown
2002
- 2002-02-13 US US10/073,326 patent/US7022860B2/en not_active Expired - Fee Related
2004
- 2004-09-08 NO NO20043765A patent/NO20043765L/no not_active Application Discontinuation
2005
- 2005-11-09 US US11/269,828 patent/US7238812B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
US6372735B1 (en)	2002-04-16
PT1026167E (pt)	2003-07-31
DE69811930T2 (de)	2003-12-18
NO20043765L (no)	2000-05-18
EP1026167A4 (fr)	2001-07-11
WO1999016770A1 (fr)	1999-04-08
AU744636B2 (en)	2002-02-28
US7238812B2 (en)	2007-07-03
US20060074074A1 (en)	2006-04-06
US7022860B2 (en)	2006-04-04
PL339544A1 (en)	2000-12-18
CN1523019A (zh)	2004-08-25
US20020137739A1 (en)	2002-09-26
NO20001500D0 (no)	2000-03-23
DE69811930D1 (de)	2003-04-10
CA2305307A1 (fr)	1999-04-08
DK1026167T3 (da)	2003-05-26
KR20010030784A (ko)	2001-04-16
SK4252000A3 (en)	2000-10-09
EP1026167A1 (fr)	2000-08-09
HK1032782A1 (en)	2002-08-30
NZ503601A (en)	2002-02-01
ATE233764T1 (de)	2003-03-15
BR9814055B1 (pt)	2009-05-05
ES2191963T3 (es)	2003-09-16
HUP0004020A2 (hu)	2001-09-28
JP3188482B2 (ja)	2001-07-16
ID24101A (id)	2000-07-06
TR200000808T2 (tr)	2000-08-21
TW510902B (en)	2002-11-21
NO20001500L (no)	2000-05-18
BR9814055A (pt)	2000-09-26
KR100389140B1 (ko)	2003-06-25
RU2198885C2 (ru)	2003-02-20
AU9186998A (en)	1999-04-23
CN1312135C (zh)	2007-04-25
HUP0004020A3 (en)	2002-12-28
CN1155599C (zh)	2004-06-30
EP1026167B1 (fr)	2003-03-05
IL135303A0 (en)	2001-05-20
CN1278262A (zh)	2000-12-27
CA2305307C (fr)	2004-11-30
SK283869B6 (sk)	2004-03-02

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