NO312547B1 - Indolderivater nyttige som endotelinreseptorantagonister - Google Patents

Indolderivater nyttige som endotelinreseptorantagonister Download PDF

Info

Publication number: NO312547B1
Authority: NO; Norway
Prior art keywords: compound; formula; mmol; methyl; solution
Prior art date: 1996-05-09

Application number

NO19985225A

Other languages

English (en)

Norwegian (no)

Other versions

NO985225D0 (no

NO985225L (no

Inventor

David James Rawson

Kevin Neil Dack

Roger Peter Dickinson

Kim James

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.)

1996-05-09

Filing date

1998-11-09

Publication date

2002-05-27

1998-11-09 Application filed by Pfizer filed Critical Pfizer

1998-11-09 Publication of NO985225D0 publication Critical patent/NO985225D0/no

1998-11-09 Publication of NO985225L publication Critical patent/NO985225L/no

2002-05-27 Publication of NO312547B1 publication Critical patent/NO312547B1/no

Links

239000002308 endothelin receptor antagonist Substances 0.000 title description 7
229940118365 Endothelin receptor antagonist Drugs 0.000 title description 6
150000002475 indoles Chemical class 0.000 title description 5
229940054051 antipsychotic indole derivative Drugs 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims description 205
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 59
238000000034 method Methods 0.000 claims description 59
238000002360 preparation method Methods 0.000 claims description 31
238000006243 chemical reaction Methods 0.000 claims description 30
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 17
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 14
229910002092 carbon dioxide Chemical group 0.000 claims description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 10
229910052740 iodine Inorganic materials 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 9
239000003054 catalyst Substances 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 6
229910052763 palladium Inorganic materials 0.000 claims description 6
208000002815 pulmonary hypertension Diseases 0.000 claims description 6
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125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
229940079593 drug Drugs 0.000 claims description 5
201000006370 kidney failure Diseases 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
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206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 4
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GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
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239000002585 base Substances 0.000 claims description 4
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125000003831 tetrazolyl group Chemical class 0.000 claims description 4
SLLFVLKNXABYGI-UHFFFAOYSA-N 1,2,3-benzoxadiazole Chemical group C1=CC=C2ON=NC2=C1 SLLFVLKNXABYGI-UHFFFAOYSA-N 0.000 claims description 3
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PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 3
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231100000268 induced nephrotoxicity Toxicity 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
230000000269 nucleophilic effect Effects 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
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125000005493 quinolyl group Chemical group 0.000 claims description 3
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YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 2
239000002671 adjuvant Substances 0.000 claims description 2
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238000010168 coupling process Methods 0.000 claims description 2
238000005859 coupling reaction Methods 0.000 claims description 2
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125000002883 imidazolyl group Chemical class 0.000 claims description 2
125000002757 morpholinyl group Chemical group 0.000 claims description 2
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125000001715 oxadiazolyl group Chemical class 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
125000001424 substituent group Chemical group 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
125000001425 triazolyl group Chemical class 0.000 claims description 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 255
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OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 171
239000000243 solution Substances 0.000 description 147
238000005160 1H NMR spectroscopy Methods 0.000 description 82
239000000203 mixture Substances 0.000 description 77
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 75
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 60
239000000047 product Substances 0.000 description 58
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 54
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HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 42
239000002904 solvent Substances 0.000 description 42
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
238000003818 flash chromatography Methods 0.000 description 39
239000012299 nitrogen atmosphere Substances 0.000 description 36
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 34
239000007787 solid Substances 0.000 description 34
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
-1 alkali metal salts Chemical class 0.000 description 30
229910052943 magnesium sulfate Inorganic materials 0.000 description 30
235000019341 magnesium sulphate Nutrition 0.000 description 30
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
238000010992 reflux Methods 0.000 description 27
239000003921 oil Substances 0.000 description 25
235000019198 oils Nutrition 0.000 description 25
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
239000003480 eluent Substances 0.000 description 23
239000011541 reaction mixture Substances 0.000 description 23
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 23
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 22
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 19
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
101150041968 CDC13 gene Proteins 0.000 description 18
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 18
239000012267 brine Substances 0.000 description 18
238000003756 stirring Methods 0.000 description 17
229940124530 sulfonamide Drugs 0.000 description 17
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
239000006260 foam Substances 0.000 description 16
238000012360 testing method Methods 0.000 description 16
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ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 15
238000001816 cooling Methods 0.000 description 14
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IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 13
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 13
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 13
150000003456 sulfonamides Chemical class 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
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238000004458 analytical method Methods 0.000 description 12
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NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
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PXHJDPPKNUGKPM-UHFFFAOYSA-N 6-bromo-1-methylindole Chemical compound C1=C(Br)C=C2N(C)C=CC2=C1 PXHJDPPKNUGKPM-UHFFFAOYSA-N 0.000 description 5
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239000005457 ice water Substances 0.000 description 5
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
QCVIFBRTTLMEOV-FUKQNADPSA-M sodium;(2r)-2-[[(2r)-2-[[(2s)-2-[[(2s,6r)-2,6-dimethylpiperidine-1-carbonyl]amino]-4,4-dimethylpentanoyl]amino]-3-(1-methoxycarbonylindol-3-yl)propanoyl]amino]hexanoate Chemical compound [Na+].N([C@@H](CC(C)(C)C)C(=O)N[C@H](CC=1C2=CC=CC=C2N(C(=O)OC)C=1)C(=O)N[C@H](CCCC)C([O-])=O)C(=O)N1[C@@H](C)CCC[C@H]1C QCVIFBRTTLMEOV-FUKQNADPSA-M 0.000 description 5
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- 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
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Urology & Nephrology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Vascular Medicine (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Pulmonology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)

NO19985225A 1996-05-09 1998-11-09 Indolderivater nyttige som endotelinreseptorantagonister NO312547B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9609641.7A GB9609641D0 (en)	1996-05-09	1996-05-09	Compounds useful in therapy
PCT/EP1997/001882 WO1997043260A1 (en)	1996-05-09	1997-04-11	Indole derivatives useful as endothelin receptor antagonists

Publications (3)

Publication Number	Publication Date
NO985225D0 NO985225D0 (no)	1998-11-09
NO985225L NO985225L (no)	1998-11-09
NO312547B1 true NO312547B1 (no)	2002-05-27

Family

ID=10793387

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19985225A NO312547B1 (no)	1996-05-09	1998-11-09	Indolderivater nyttige som endotelinreseptorantagonister

Country Status (43)

Country	Link
US (4)	US6017945A (es)
EP (1)	EP0901470B1 (es)
JP (1)	JP3245179B2 (es)
KR (1)	KR100331217B1 (es)
CN (1)	CN1124262C (es)
AP (1)	AP830A (es)
AR (1)	AR007030A1 (es)
AT (1)	ATE263151T1 (es)
AU (1)	AU717849B2 (es)
BG (1)	BG102873A (es)
BR (1)	BR9709072A (es)
CA (1)	CA2253876A1 (es)
CO (1)	CO4650036A1 (es)
CZ (1)	CZ292928B6 (es)
DE (1)	DE69728392T2 (es)
DK (1)	DK0901470T3 (es)
DZ (1)	DZ2227A1 (es)
EA (1)	EA001471B1 (es)
ES (1)	ES2218675T3 (es)
GB (1)	GB9609641D0 (es)
HK (1)	HK1019149A1 (es)
HN (1)	HN1997000058A (es)
HR (1)	HRP970249B1 (es)
HU (1)	HUP9901245A3 (es)
ID (1)	ID16878A (es)
IL (1)	IL125903A0 (es)
IS (1)	IS1856B (es)
MA (1)	MA26428A1 (es)
NO (1)	NO312547B1 (es)
NZ (1)	NZ332640A (es)
OA (1)	OA10896A (es)
PE (1)	PE65098A1 (es)
PL (1)	PL329725A1 (es)
PT (1)	PT901470E (es)
SI (1)	SI0901470T1 (es)
SK (1)	SK150398A3 (es)
TN (1)	TNSN97078A1 (es)
TR (1)	TR199802269T2 (es)
TW (1)	TW491838B (es)
UA (1)	UA50767C2 (es)
UY (1)	UY24546A1 (es)
WO (1)	WO1997043260A1 (es)
ZA (1)	ZA973963B (es)

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GB0016162D0 (en) *	2000-06-30	2000-08-23	Cancer Res Campaign Tech	Indole-3-acetic acid derivatives
US20050203166A1 (en) *	2000-06-30	2005-09-15	Cancer Research Technology Limited	Indole-3-acetic acid derivatives
JP4399253B2 (ja)	2001-06-20	2010-01-13	ワイス	プラスミノゲンアクチベーターインヒビター−１（ｐａｉ−１）のインヒビターとしての、置換されたインドール酸誘導体
TWI224101B (en)	2001-06-20	2004-11-21	Wyeth Corp	Substituted naphthyl indole derivatives as inhibitors of plasminogen activator inhibitor type-1 (PAI-1)
AR037097A1 (es)	2001-10-05	2004-10-20	Novartis Ag	Compuestos acilsulfonamidas, composiciones farmaceuticas y el uso de dichos compuestos para la preparacion de un medicamento
UA80453C2 (en)	2002-12-10	2007-09-25		Derivatives of substituted dyhydropyranoindol-3,4-dion as inhibitors of plasminogen activator inhibitor-1 (pai-1)
JP2006510672A (ja)	2002-12-10	2006-03-30	ワイス	プラスミノーゲン活性化因子の阻害因子−１（ｐａｉ−１）の阻害剤としての置換インドールオキソ−アセチルアミノ酢酸誘導体
DE60306548T2 (de)	2002-12-10	2007-06-21	Wyeth	Substituierte 3-carbonyl-1-yl-essigsäure-derivate als plasminogen aktivator inhibitor(pai-1) inhibitoren
DE60306547T2 (de)	2002-12-10	2007-06-28	Wyeth	Substituierte 3-alkyl- und 3-arylalkyl-1h-indol-1-yl-essigsäure-derivate als plasminogen-aktivator
DE60324183D1 (en)	2002-12-10	2008-11-27	Wyeth Corp	Aryl-, aryloxy- und alkyloxysubstituierte 1h-indol-3-yl-glyoxylsäurederivateals inhibitoren des plasminogenaktivatorinhibitors-1 (pai-1)
BRPI0406883A (pt) *	2003-01-22	2006-01-03	Lilly Co Eli	Composto, composição farmacêutica, método de tratar um distúrbio, e, uso de um composto
US7268159B2 (en)	2003-09-25	2007-09-11	Wyeth	Substituted indoles
US7351726B2 (en)	2003-09-25	2008-04-01	Wyeth	Substituted oxadiazolidinediones
US7163954B2 (en)	2003-09-25	2007-01-16	Wyeth	Substituted naphthyl benzothiophene acids
US7332521B2 (en)	2003-09-25	2008-02-19	Wyeth	Substituted indoles
US7342039B2 (en)	2003-09-25	2008-03-11	Wyeth	Substituted indole oximes
US7442805B2 (en)	2003-09-25	2008-10-28	Wyeth	Substituted sulfonamide-indoles
US7582773B2 (en)	2003-09-25	2009-09-01	Wyeth	Substituted phenyl indoles
US7411083B2 (en)	2003-09-25	2008-08-12	Wyeth	Substituted acetic acid derivatives
US7265148B2 (en)	2003-09-25	2007-09-04	Wyeth	Substituted pyrrole-indoles
US7446201B2 (en)	2003-09-25	2008-11-04	Wyeth	Substituted heteroaryl benzofuran acids
US7420083B2 (en)	2003-09-25	2008-09-02	Wyeth	Substituted aryloximes
US7141592B2 (en)	2003-09-25	2006-11-28	Wyeth	Substituted oxadiazolidinediones
JP2005109006A (ja) *	2003-09-29	2005-04-21	Tdk Corp	高電圧貫通型コンデンサ及びマグネトロン
HN2004000536A (es) *	2003-12-16	2009-02-18	Wyeth Corp	Un procediemiento de sintesis para la alquilacion reductiva de la posicon c-3 de indoles
CN101039936A (zh)	2004-08-23	2007-09-19	惠氏公司	作为i－型纤溶酶原激活剂抑制剂(pai－1)调节剂用于治疗血栓形成和心血管疾病的唑基－萘基酸
CN101263115A (zh)	2005-08-17	2008-09-10	惠氏公司	经取代吲哚和其用途
US20100022568A1 (en) *	2006-04-13	2010-01-28	Actelion Pharmaceeuticals Ltd.	Endothelin receptor antagonists for early stage idiopathic pulmonary fibrosis
DE102008030206A1 (de)	2008-06-25	2009-12-31	Bayer Schering Pharma Aktiengesellschaft	3-Cyanoalky- und 3-Hydroxyalkyl-Indole und ihre Verwendung
DE102008030207A1 (de)	2008-06-25	2009-12-31	Bayer Schering Pharma Aktiengesellschaft	Substituierte 7-Sulfanylmethyl-, 7-Sulfinylmethyl- und 7-Sulfonylmethyl-Indole und ihre Verwendung
CN106674065A (zh) *	2016-12-07	2017-05-17	贵州大学	一种5‑卤代‑2‑烷氧基‑4‑甲苯磺酰氯制备方法
GB201817038D0 (en) *	2018-10-19	2018-12-05	Inflazome Ltd	Novel processes
AU2020229779A1 (en)	2019-02-27	2021-09-09	The Regents Of The University Of California	Azepino-indoles and other heterocycles for treating brain disorders

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GB9317096D0 (en) *	1993-08-17	1993-09-29	Pfizer Ltd	Indoles

1996
- 1996-05-09 GB GBGB9609641.7A patent/GB9609641D0/en active Pending
1997
- 1997-04-01 TW TW086104171A patent/TW491838B/zh not_active IP Right Cessation
- 1997-04-11 SK SK1503-98A patent/SK150398A3/sk unknown
- 1997-04-11 ES ES97920690T patent/ES2218675T3/es not_active Expired - Lifetime
- 1997-04-11 BR BR9709072A patent/BR9709072A/pt active Search and Examination
- 1997-04-11 DE DE1997628392 patent/DE69728392T2/de not_active Expired - Fee Related
- 1997-04-11 NZ NZ332640A patent/NZ332640A/en unknown
- 1997-04-11 AT AT97920690T patent/ATE263151T1/de not_active IP Right Cessation
- 1997-04-11 TR TR1998/02269T patent/TR199802269T2/xx unknown
- 1997-04-11 US US09/147,096 patent/US6017945A/en not_active Expired - Fee Related
- 1997-04-11 DK DK97920690T patent/DK0901470T3/da active
- 1997-04-11 KR KR1019980709023A patent/KR100331217B1/ko not_active IP Right Cessation
- 1997-04-11 EP EP97920690A patent/EP0901470B1/en not_active Expired - Lifetime
- 1997-04-11 IL IL12590397A patent/IL125903A0/xx unknown
- 1997-04-11 CZ CZ19983582A patent/CZ292928B6/cs not_active IP Right Cessation
- 1997-04-11 CA CA002253876A patent/CA2253876A1/en not_active Abandoned
- 1997-04-11 PT PT97920690T patent/PT901470E/pt unknown
- 1997-04-11 WO PCT/EP1997/001882 patent/WO1997043260A1/en active IP Right Grant
- 1997-04-11 PL PL97329725A patent/PL329725A1/xx unknown
- 1997-04-11 HU HU9901245A patent/HUP9901245A3/hu unknown
- 1997-04-11 EA EA199800908A patent/EA001471B1/ru not_active IP Right Cessation
- 1997-04-11 CN CN97194016A patent/CN1124262C/zh not_active Expired - Fee Related
- 1997-04-11 UA UA98115906A patent/UA50767C2/uk unknown
- 1997-04-11 SI SI9730646T patent/SI0901470T1/xx unknown
- 1997-04-11 AU AU26978/97A patent/AU717849B2/en not_active Ceased
- 1997-04-11 JP JP54042397A patent/JP3245179B2/ja not_active Expired - Fee Related
- 1997-04-29 HN HN1997000058A patent/HN1997000058A/es unknown
- 1997-05-02 PE PE1997000345A patent/PE65098A1/es not_active Application Discontinuation
- 1997-05-07 TN TNTNSN97078A patent/TNSN97078A1/fr unknown
- 1997-05-07 MA MA24599A patent/MA26428A1/fr unknown
- 1997-05-07 AR ARP970101888A patent/AR007030A1/es not_active Application Discontinuation
- 1997-05-07 UY UY24546A patent/UY24546A1/es not_active IP Right Cessation
- 1997-05-07 CO CO97024471A patent/CO4650036A1/es unknown
- 1997-05-07 DZ DZ970074A patent/DZ2227A1/fr active
- 1997-05-07 ID IDP971517A patent/ID16878A/id unknown
- 1997-05-08 AP APAP/P/1997/000982A patent/AP830A/en active
- 1997-05-08 ZA ZA973963A patent/ZA973963B/xx unknown
- 1997-05-09 HR HR970249A patent/HRP970249B1/xx not_active IP Right Cessation
1998
- 1998-08-28 IS IS4838A patent/IS1856B/is unknown
- 1998-10-09 OA OA9800192A patent/OA10896A/en unknown
- 1998-10-27 BG BG102873A patent/BG102873A/xx unknown
- 1998-11-09 NO NO19985225A patent/NO312547B1/no not_active IP Right Cessation
1999
- 1999-10-06 HK HK99104349A patent/HK1019149A1/xx not_active IP Right Cessation
- 1999-10-07 US US09/414,361 patent/US6136843A/en not_active Expired - Fee Related
2000
- 2000-04-24 US US09/556,651 patent/US6306852B1/en not_active Expired - Fee Related
2001
- 2001-01-09 US US09/756,835 patent/US6384070B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
JPH11508285A (ja)	1999-07-21
PE65098A1 (es)	1998-10-29
CA2253876A1 (en)	1997-11-20
EA001471B1 (ru)	2001-04-23
GB9609641D0 (en)	1996-07-10
HRP970249B1 (en)	2003-06-30
DZ2227A1 (fr)	2002-12-25
TW491838B (en)	2002-06-21
US6306852B1 (en)	2001-10-23
PT901470E (pt)	2004-07-30
CZ358298A3 (cs)	1999-08-11
AR007030A1 (es)	1999-10-13
ATE263151T1 (de)	2004-04-15
UY24546A1 (es)	2000-09-29
AU2697897A (en)	1997-12-05
TNSN97078A1 (fr)	2005-03-15
ID16878A (id)	1997-11-20
EP0901470B1 (en)	2004-03-31
DE69728392D1 (de)	2004-05-06
CZ292928B6 (cs)	2004-01-14
ZA973963B (en)	1998-11-09
DK0901470T3 (da)	2004-07-12
US6384070B2 (en)	2002-05-07
PL329725A1 (en)	1999-04-12
IS4838A (is)	1998-08-28
HUP9901245A2 (hu)	1999-08-30
OA10896A (en)	2001-10-11
US20010014677A1 (en)	2001-08-16
EA199800908A1 (ru)	1999-06-24
TR199802269T2 (xx)	2001-12-21
NZ332640A (en)	2001-03-30
DE69728392T2 (de)	2005-01-13
KR100331217B1 (ko)	2002-05-09
BG102873A (en)	1999-11-30
EP0901470A1 (en)	1999-03-17
SK150398A3 (en)	1999-03-12
IL125903A0 (en)	1999-04-11
IS1856B (is)	2003-02-21
HRP970249A2 (en)	1998-06-30
HUP9901245A3 (en)	2002-01-28
JP3245179B2 (ja)	2002-01-07
MA26428A1 (fr)	2004-12-20
ES2218675T3 (es)	2004-11-16
NO985225D0 (no)	1998-11-09
HN1997000058A (es)	1997-06-26
NO985225L (no)	1998-11-09
AU717849B2 (en)	2000-04-06
CO4650036A1 (es)	1998-09-03
US6136843A (en)	2000-10-24
AP9700982A0 (en)	1997-07-31
AP830A (en)	2000-05-03
BR9709072A (pt)	1999-08-03
WO1997043260A1 (en)	1997-11-20
CN1216531A (zh)	1999-05-12
KR20000010879A (ko)	2000-02-25
US6017945A (en)	2000-01-25
HK1019149A1 (en)	2000-01-14
CN1124262C (zh)	2003-10-15
UA50767C2 (uk)	2002-11-15
SI0901470T1 (en)	2004-08-31

Legal Events

Date	Code	Title	Description
2005-11-28	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO312547B1 (no)	2002-05-27	Indolderivater nyttige som endotelinreseptorantagonister
KR100901221B1 (ko)	2009-06-08	무스카린성 작용제
US20020072616A1 (en)	2002-06-13	3-azabicyclo[3.1.0]hexane derivatives useful in therapy
JP3421323B2 (ja)	2003-06-30	ピペリジンｃｃｒ−３受容体拮抗薬
US5284862A (en)	1994-02-08	Derivatives of 2-carboxyindoles having pharmaceutical activity
JPH07509465A (ja)	1995-10-19	エンドセリン受容体アンタゴニスト
KR101464778B1 (ko)	2014-11-24	에티닐인돌 화합물
KR20110023895A (ko)	2011-03-08	치환된 ７-술파닐메틸, ７-술피닐메틸 및 ７-술포닐메틸 인돌, 및 그의 용도
CA2112689A1 (en)	1993-02-04	Indoles
WO2002044168A2 (en)	2002-06-06	Indole-type inhibitors of p38 kinase
NZ233645A (en)	1992-06-25	3-(hetero)aryl-substituted-3,4 dehydropiperidine derivatives; preparatory processes and pharmaceutical compositions
JPH09506083A (ja)	1997-06-17	フエニルインドール化合物
US20040142940A1 (en)	2004-07-22	Indole-type derivatives as inhibitors of p38 kinase
NO171211B (no)	1992-11-02	Analogifremgangsmaate for fremstilling av terapeutisk aktive 1,3-dioksaner
EP0780388B1 (en)	2001-08-16	5HT1Dalpha and 5HT2A ligands
AP899A (en)	2000-11-17	Indole derivatives useful in therapy.
MXPA99000354A (es)	2002-06-05	Un sistema y metodo para permitir manipulacion deimagenes graficas para formar una imagen grafica
JP2987643B2 (ja)	1999-12-06	インドール誘導体及びこれを含有する医薬
JP3558153B2 (ja)	2004-08-25	Ｎ−ヒドロキシ尿素誘導体
JP2000508297A (ja)	2000-07-04	抗高血圧活性を有する新規キナゾリン―４―アミノ―２―（ピペリジン―１―イル―４―置換）誘導体並びにその製造法および医薬用途