IL133079A - Salts-1 (-2-acetylimidazole-1-ylalkyl), as tachykinin antagonists, their preparation and pharmaceutical preparations containing them - Google Patents

Salts-1 (-2-acetylimidazole-1-ylalkyl), as tachykinin antagonists, their preparation and pharmaceutical preparations containing them

Info

Publication number: IL133079A
Authority: IL; Israel
Prior art keywords: phenyl; compound; ch3s03; alkyl; fluoro
Prior art date: 1997-06-18

Application number

IL13307998A

Other languages

English (en)

Hebrew (he)

Other versions

IL133079A0 (en

Original Assignee

Pfizer

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.)

1997-06-18

Filing date

1998-06-05

Publication date

2004-06-01

1998-06-05 Application filed by Pfizer filed Critical Pfizer

1998-06-05 Priority to IL15562198A priority Critical patent/IL155621A0/xx

2001-03-19 Publication of IL133079A0 publication Critical patent/IL133079A0/xx

2004-06-01 Publication of IL133079A publication Critical patent/IL133079A/en

Links

238000002360 preparation method Methods 0.000 title claims description 169
239000005557 antagonist Substances 0.000 title claims description 10
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
102000003141 Tachykinin Human genes 0.000 title description 3
SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical class C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 title description 3
108060008037 tachykinin Proteins 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 134
-1 fluoro (C1-C4) alkyl Chemical group 0.000 claims abstract description 90
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 64
150000001450 anions Chemical class 0.000 claims abstract description 17
125000001424 substituent group Chemical group 0.000 claims abstract description 15
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 14
125000002947 alkylene group Chemical group 0.000 claims abstract description 12
229910052799 carbon Inorganic materials 0.000 claims abstract description 11
125000005843 halogen group Chemical group 0.000 claims abstract description 11
125000001624 naphthyl group Chemical group 0.000 claims abstract description 10
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 9
125000001544 thienyl group Chemical group 0.000 claims abstract description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 8
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 7
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 7
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 6
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 5
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims abstract description 3
239000005977 Ethylene Substances 0.000 claims abstract description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 3
125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims abstract description 3
125000001041 indolyl group Chemical group 0.000 claims abstract description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 3
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 3
239000001301 oxygen Substances 0.000 claims abstract description 3
229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
125000004076 pyridyl group Chemical group 0.000 claims abstract description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 40
238000000034 method Methods 0.000 claims description 38
208000035475 disorder Diseases 0.000 claims description 22
201000010099 disease Diseases 0.000 claims description 18
125000000217 alkyl group Chemical group 0.000 claims description 17
AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims description 16
125000001153 fluoro group Chemical group F* 0.000 claims description 16
238000006243 chemical reaction Methods 0.000 claims description 15
125000003545 alkoxy group Chemical group 0.000 claims description 14
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 12
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 10
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 10
125000001309 chloro group Chemical group Cl* 0.000 claims description 10
230000000694 effects Effects 0.000 claims description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 9
108010072901 Tachykinin Receptors Proteins 0.000 claims description 9
102000007124 Tachykinin Receptors Human genes 0.000 claims description 9
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 9
206010020751 Hypersensitivity Diseases 0.000 claims description 8
208000002193 Pain Diseases 0.000 claims description 8
208000026935 allergic disease Diseases 0.000 claims description 8
210000003169 central nervous system Anatomy 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
208000004296 neuralgia Diseases 0.000 claims description 8
SBYHFKPVCBCYGV-UHFFFAOYSA-O 1-azoniabicyclo[2.2.2]octane Chemical compound C1CC2CC[NH+]1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-O 0.000 claims description 7
230000008569 process Effects 0.000 claims description 7
238000011282 treatment Methods 0.000 claims description 7
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims description 6
201000004624 Dermatitis Diseases 0.000 claims description 5
208000006673 asthma Diseases 0.000 claims description 5
229910052739 hydrogen Inorganic materials 0.000 claims description 5
208000019901 Anxiety disease Diseases 0.000 claims description 4
241000894006 Bacteria Species 0.000 claims description 4
208000001387 Causalgia Diseases 0.000 claims description 4
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
208000000094 Chronic Pain Diseases 0.000 claims description 4
208000023890 Complex Regional Pain Syndromes Diseases 0.000 claims description 4
206010011224 Cough Diseases 0.000 claims description 4
208000011231 Crohn disease Diseases 0.000 claims description 4
206010012289 Dementia Diseases 0.000 claims description 4
206010012438 Dermatitis atopic Diseases 0.000 claims description 4
206010012442 Dermatitis contact Diseases 0.000 claims description 4
208000032131 Diabetic Neuropathies Diseases 0.000 claims description 4
208000034347 Faecal incontinence Diseases 0.000 claims description 4
206010021639 Incontinence Diseases 0.000 claims description 4
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
208000019693 Lung disease Diseases 0.000 claims description 4
208000019695 Migraine disease Diseases 0.000 claims description 4
206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 4
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208000028017 Psychotic disease Diseases 0.000 claims description 4
241000159243 Toxicodendron radicans Species 0.000 claims description 4
108010046334 Urease Proteins 0.000 claims description 4
206010047700 Vomiting Diseases 0.000 claims description 4
230000001154 acute effect Effects 0.000 claims description 4
208000005298 acute pain Diseases 0.000 claims description 4
230000007815 allergy Effects 0.000 claims description 4
230000036506 anxiety Effects 0.000 claims description 4
206010003246 arthritis Diseases 0.000 claims description 4
201000008937 atopic dermatitis Diseases 0.000 claims description 4
208000010668 atopic eczema Diseases 0.000 claims description 4
125000001246 bromo group Chemical group Br* 0.000 claims description 4
206010009887 colitis Diseases 0.000 claims description 4
208000014439 complex regional pain syndrome type 2 Diseases 0.000 claims description 4
208000010247 contact dermatitis Diseases 0.000 claims description 4
201000003146 cystitis Diseases 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
230000002496 gastric effect Effects 0.000 claims description 4
208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 4
230000009610 hypersensitivity Effects 0.000 claims description 4
208000027866 inflammatory disease Diseases 0.000 claims description 4
208000002551 irritable bowel syndrome Diseases 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
206010027599 migraine Diseases 0.000 claims description 4
208000005877 painful neuropathy Diseases 0.000 claims description 4
208000033808 peripheral neuropathy Diseases 0.000 claims description 4
208000000187 Abnormal Reflex Diseases 0.000 claims description 3
241000590002 Helicobacter pylori Species 0.000 claims description 3
206010039085 Rhinitis allergic Diseases 0.000 claims description 3
201000010105 allergic rhinitis Diseases 0.000 claims description 3
229940037467 helicobacter pylori Drugs 0.000 claims description 3
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
206010020745 hyperreflexia Diseases 0.000 claims description 3
230000035859 hyperreflexia Effects 0.000 claims description 3
125000002346 iodo group Chemical group I* 0.000 claims description 3
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
229910002651 NO3 Inorganic materials 0.000 claims description 2
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
229910021653 sulphate ion Inorganic materials 0.000 claims description 2
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 2
QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 claims 1
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims 1
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical class C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims 1
125000002252 acyl group Chemical group 0.000 abstract description 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 249
239000002904 solvent Substances 0.000 description 136
239000000203 mixture Substances 0.000 description 123
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
235000011468 Albizia julibrissin Nutrition 0.000 description 105
241001070944 Mimosa Species 0.000 description 105
239000000243 solution Substances 0.000 description 105
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 99
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 74
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 65
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 42
101150041968 CDC13 gene Proteins 0.000 description 40
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
239000000741 silica gel Substances 0.000 description 39
229910002027 silica gel Inorganic materials 0.000 description 39
239000003921 oil Substances 0.000 description 38
235000019198 oils Nutrition 0.000 description 38
239000012074 organic phase Substances 0.000 description 37
229910052938 sodium sulfate Inorganic materials 0.000 description 37
235000011152 sodium sulphate Nutrition 0.000 description 37
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 32
238000005160 1H NMR spectroscopy Methods 0.000 description 31
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
239000012267 brine Substances 0.000 description 25
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 24
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OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 20
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238000005481 NMR spectroscopy Methods 0.000 description 17
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102100024304 Protachykinin-1 Human genes 0.000 description 10
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KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
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101800000399 Neurokinin A Proteins 0.000 description 8
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HEAUFJZALFKPBA-YRVBCFNBSA-N Neurokinin A Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)O)C1=CC=CC=C1 HEAUFJZALFKPBA-YRVBCFNBSA-N 0.000 description 8
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MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
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QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 6
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NZFGRMZVCZOLHP-UHFFFAOYSA-N 4-cyclohexyl-1-azabicyclo[2.2.2]octane Chemical compound C1CCCCC1C1(CC2)CCN2CC1 NZFGRMZVCZOLHP-UHFFFAOYSA-N 0.000 description 4
CSKNWIPXDBBWRW-UHFFFAOYSA-N 4-phenyl-1-azabicyclo[2.2.2]octane Chemical compound C1CN(CC2)CCC21C1=CC=CC=C1 CSKNWIPXDBBWRW-UHFFFAOYSA-N 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
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JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
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230000015572 biosynthetic process Effects 0.000 description 4
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CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
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TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 4
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IL13307998A 1997-06-18 1998-06-05 Salts-1 (-2-acetylimidazole-1-ylalkyl), as tachykinin antagonists, their preparation and pharmaceutical preparations containing them IL133079A (en)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
IL15562198A IL155621A0 (en)	1997-06-18	1998-06-05	Quaternary ammonium compounds as tachykinin antagonists

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GBGB9712882.1A GB9712882D0 (en)	1997-06-18	1997-06-18	Quaternary ammonium compounds
PCT/EP1998/003500 WO1998057972A1 (en)	1997-06-18	1998-06-05	Quaternary ammonium compounds as tachykinin antagonists

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IL133079A0 IL133079A0 (en)	2001-03-19
IL133079A true IL133079A (en)	2004-06-01

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IL15562198A IL155621A0 (en)	1997-06-18	1998-06-05	Quaternary ammonium compounds as tachykinin antagonists
IL13307998A IL133079A (en)	1997-06-18	1998-06-05	Salts-1 (-2-acetylimidazole-1-ylalkyl), as tachykinin antagonists, their preparation and pharmaceutical preparations containing them

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EP (1)	EP0994876B1 (de)
JP (1)	JP3280993B2 (de)
KR (1)	KR100345389B1 (de)
CN (1)	CN1199971C (de)
AP (1)	AP947A (de)
AR (1)	AR012249A1 (de)
AT (1)	ATE275564T1 (de)
AU (1)	AU726027B2 (de)
BG (1)	BG63341B1 (de)
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DE (1)	DE69826129T2 (de)
DZ (1)	DZ2524A1 (de)
EA (1)	EA002424B1 (de)
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GB (1)	GB9712882D0 (de)
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HR (1)	HRP980337B1 (de)
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ID (1)	ID23410A (de)
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UA (1)	UA62966C2 (de)
UY (1)	UY25045A1 (de)
WO (1)	WO1998057972A1 (de)
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EP1043031A4 (de) *	1997-12-26	2007-05-02	Astellas Pharma Inc	Medizinische zusammensetzungen mit verzögerter wirkstoffabgabe
JP4546589B2 (ja) *	1998-04-23	2010-09-15	武田薬品工業株式会社	ナフタレン誘導体
WO2001095904A1 (en) *	2000-06-12	2001-12-20	University Of Rochester	Method of treating symptoms of hormonal variation, including hot flashes, using tachykinin receptor antagonist
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1997
- 1997-06-18 GB GBGB9712882.1A patent/GB9712882D0/en active Pending
1998
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1999
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Also Published As

Publication number	Publication date
IL155621A0 (en)	2003-11-23
CA2291975A1 (en)	1998-12-23
NO995782D0 (no)	1999-11-25
AU726027B2 (en)	2000-10-26
ZA985239B (en)	1999-12-17
IL133079A0 (en)	2001-03-19
SK283346B6 (sk)	2003-06-03
OA11235A (en)	2003-07-09
TW479055B (en)	2002-03-11
NO995782L (no)	2000-02-16
IS5269A (is)	1999-11-23
YU64699A (sh)	2002-06-19
PL189557B1 (pl)	2005-08-31
DE69826129D1 (de)	2004-10-14
PL337713A1 (en)	2000-08-28
ID23410A (id)	2000-04-20
EP0994876A1 (de)	2000-04-26
JP2000513030A (ja)	2000-10-03
JP3280993B2 (ja)	2002-05-13
NZ501286A (en)	2000-07-28
AU8215398A (en)	1999-01-04
TR199903135T2 (xx)	2000-04-21
CN1199971C (zh)	2005-05-04
HUP0003962A2 (hu)	2001-04-28
BG63341B1 (bg)	2001-10-31
BR9810619A (pt)	2000-09-12
CA2291975C (en)	2004-02-10
AR012249A1 (es)	2000-09-27
SI0994876T1 (en)	2005-02-28
HRP980337B1 (en)	2003-02-28
PT994876E (pt)	2005-01-31
TNSN98089A1 (fr)	2005-03-15
GB9712882D0 (en)	1997-08-20
PA8452501A1 (es)	2000-05-24
UA62966C2 (en)	2004-01-15
BG103919A (en)	2001-07-31
MY136376A (en)	2008-09-30
AP947A (en)	2001-03-08
SK174499A3 (en)	2001-05-10
EA199900986A1 (ru)	2000-06-26
KR20010013909A (ko)	2001-02-26
US6207678B1 (en)	2001-03-27
ES2227856T3 (es)	2005-04-01
KR100345389B1 (ko)	2002-07-24
PE80099A1 (es)	1999-08-25
EA002424B1 (ru)	2002-04-25
EP0994876B1 (de)	2004-09-08
DZ2524A1 (fr)	2003-02-01
ATE275564T1 (de)	2004-09-15
CN1260795A (zh)	2000-07-19
MA26509A1 (fr)	2004-12-20
UY25045A1 (es)	2000-09-29
CO4940478A1 (es)	2000-07-24
HRP980337A2 (en)	1999-02-28
HN1998000087A (es)	1998-10-22
WO1998057972A1 (en)	1998-12-23
AP9801262A0 (en)	1998-06-30
DE69826129T2 (de)	2005-09-22
HUP0003962A3 (en)	2001-12-28
US6380396B1 (en)	2002-04-30

Legal Events

Date	Code	Title	Description
2004-11-10	FF	Patent granted
2009-07-27	MM9K	Patent not in force due to non-payment of renewal fees

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