DK172696B1 - Indolderivater, fremgangsmåde til fremstilling deraf og farmaceutiske præparater indeholdende forbindelserne - Google Patents

Indolderivater, fremgangsmåde til fremstilling deraf og farmaceutiske præparater indeholdende forbindelserne Download PDF

Info

Publication number: DK172696B1
Authority: DK; Denmark
Prior art keywords: formula; compound; alkyl; methyl; indole
Prior art date: 1987-08-13

Application number

DK198804554A

Other languages

Danish (da)

English (en)

Other versions

DK455488D0 (da

DK455488A (da

Inventor

Alexander William Oxford

Darko Butina

Martin Richard Owen

Original Assignee

Glaxo Group Ltd

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.)

1987-08-13

Filing date

1988-08-12

Publication date

1999-05-31

1987-08-13 Priority claimed from GB878719167A external-priority patent/GB8719167D0/en

1988-06-14 Priority claimed from GB888814002A external-priority patent/GB8814002D0/en

1988-06-17 Priority claimed from GB888814481A external-priority patent/GB8814481D0/en

1988-08-12 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

1988-08-12 Publication of DK455488D0 publication Critical patent/DK455488D0/da

1989-02-14 Publication of DK455488A publication Critical patent/DK455488A/da

1999-05-31 Application granted granted Critical

1999-05-31 Publication of DK172696B1 publication Critical patent/DK172696B1/da

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 137
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 10
150000002475 indoles Chemical class 0.000 title claims description 9
238000000034 method Methods 0.000 title abstract description 29
230000008569 process Effects 0.000 title abstract description 18
238000002360 preparation method Methods 0.000 title abstract description 12
229940054051 antipsychotic indole derivative Drugs 0.000 title description 4
150000003839 salts Chemical class 0.000 claims abstract description 37
239000012453 solvate Substances 0.000 claims abstract description 13
208000019695 Migraine disease Diseases 0.000 claims abstract description 10
238000011282 treatment Methods 0.000 claims abstract description 10
206010019233 Headaches Diseases 0.000 claims abstract description 7
231100000869 headache Toxicity 0.000 claims abstract description 7
206010027599 migraine Diseases 0.000 claims abstract description 7
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 4
208000006561 Cluster Headache Diseases 0.000 claims abstract description 4
208000019553 vascular disease Diseases 0.000 claims abstract description 4
208000018912 cluster headache syndrome Diseases 0.000 claims abstract 2
239000004480 active ingredient Substances 0.000 claims description 36
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
229910052739 hydrogen Inorganic materials 0.000 claims description 20
239000001257 hydrogen Substances 0.000 claims description 20
238000006243 chemical reaction Methods 0.000 claims description 18
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
125000000217 alkyl group Chemical group 0.000 claims description 14
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 12
125000006239 protecting group Chemical group 0.000 claims description 11
239000003814 drug Substances 0.000 claims description 9
239000003795 chemical substances by application Substances 0.000 claims description 6
AMKVXSZCKVJAGH-UHFFFAOYSA-N naratriptan Chemical group C12=CC(CCS(=O)(=O)NC)=CC=C2NC=C1C1CCN(C)CC1 AMKVXSZCKVJAGH-UHFFFAOYSA-N 0.000 claims description 6
239000000546 pharmaceutical excipient Substances 0.000 claims description 6
239000011780 sodium chloride Substances 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 5
CJTDQTJKWVZIAZ-UHFFFAOYSA-N 2-[3-(1-methylpiperidin-4-yl)-1h-indol-5-yl]ethanesulfonamide Chemical compound C1CN(C)CCC1C1=CNC2=CC=C(CCS(N)(=O)=O)C=C12 CJTDQTJKWVZIAZ-UHFFFAOYSA-N 0.000 claims description 4
150000001412 amines Chemical class 0.000 claims description 4
AZWSUNYFIOQIAH-UHFFFAOYSA-N n,n-dimethyl-2-[3-(1-methylpiperidin-4-yl)-1h-indol-5-yl]ethanesulfonamide Chemical compound C12=CC(CCS(=O)(=O)N(C)C)=CC=C2NC=C1C1CCN(C)CC1 AZWSUNYFIOQIAH-UHFFFAOYSA-N 0.000 claims description 4
GIOZJDZVQIXLKZ-UHFFFAOYSA-N n-ethyl-2-(3-piperidin-4-yl-1h-indol-5-yl)ethanesulfonamide Chemical compound C12=CC(CCS(=O)(=O)NCC)=CC=C2NC=C1C1CCNCC1 GIOZJDZVQIXLKZ-UHFFFAOYSA-N 0.000 claims description 4
239000003755 preservative agent Substances 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 3
239000002552 dosage form Substances 0.000 claims description 3
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239000008213 purified water Substances 0.000 claims description 3
208000024891 symptom Diseases 0.000 claims description 3
238000002560 therapeutic procedure Methods 0.000 claims description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
208000035475 disorder Diseases 0.000 claims description 2
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XPRXJFAFJFZWTC-UHFFFAOYSA-N hoso2 Chemical compound [O]S(O)=O XPRXJFAFJFZWTC-UHFFFAOYSA-N 0.000 claims 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
239000000337 buffer salt Substances 0.000 claims 1
230000001684 chronic effect Effects 0.000 claims 1
238000004090 dissolution Methods 0.000 claims 1
CBOLOLDRCUTBGY-UHFFFAOYSA-N n-methyl-2-(3-piperidin-4-yl-1h-indol-5-yl)ethanesulfonamide Chemical compound C12=CC(CCS(=O)(=O)NC)=CC=C2NC=C1C1CCNCC1 CBOLOLDRCUTBGY-UHFFFAOYSA-N 0.000 claims 1
230000001314 paroxysmal effect Effects 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 17
206010009094 Chronic paroxysmal hemicrania Diseases 0.000 abstract description 3
150000004677 hydrates Chemical class 0.000 abstract description 3
208000007777 paroxysmal Hemicrania Diseases 0.000 abstract description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 100
239000000203 mixture Substances 0.000 description 52
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235000019441 ethanol Nutrition 0.000 description 30
239000000243 solution Substances 0.000 description 29
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YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
239000007787 solid Substances 0.000 description 21
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 18
239000003826 tablet Substances 0.000 description 18
239000002904 solvent Substances 0.000 description 17
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HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 13
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239000000047 product Substances 0.000 description 12
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IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
229910004298 SiO 2 Inorganic materials 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
229910021529 ammonia Inorganic materials 0.000 description 10
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 9
239000002585 base Substances 0.000 description 9
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239000000377 silicon dioxide Substances 0.000 description 9
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IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
229910000041 hydrogen chloride Inorganic materials 0.000 description 8
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 8
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 7
229960001701 chloroform Drugs 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
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239000008101 lactose Substances 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
229910000029 sodium carbonate Inorganic materials 0.000 description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 6
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230000000694 effects Effects 0.000 description 6
238000003818 flash chromatography Methods 0.000 description 6
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125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
150000007522 mineralic acids Chemical class 0.000 description 6
SZXQDMYFSIGZHY-UHFFFAOYSA-N n-methyl-2-(3-piperidin-4-yl-1h-indol-5-yl)ethanesulfonamide;hydrochloride Chemical compound Cl.C12=CC(CCS(=O)(=O)NC)=CC=C2NC=C1C1CCNCC1 SZXQDMYFSIGZHY-UHFFFAOYSA-N 0.000 description 6
239000011734 sodium Substances 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
238000001914 filtration Methods 0.000 description 5
238000009472 formulation Methods 0.000 description 5
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YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 5
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 5
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239000004338 Dichlorodifluoromethane Substances 0.000 description 4
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
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UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
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239000003377 acid catalyst Substances 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
238000007796 conventional method Methods 0.000 description 4
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 4
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KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
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HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 description 2
MEVXSUZBFYZPHZ-UHFFFAOYSA-N 2-amino-3-methyl-4h-imidazol-5-one;sulfuric acid Chemical class OS(O)(=O)=O.CN1CC(=O)N=C1N MEVXSUZBFYZPHZ-UHFFFAOYSA-N 0.000 description 2
SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 2
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238000005804 alkylation reaction Methods 0.000 description 2
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OFKDAAIKGIBASY-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 description 2
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238000000338 in vitro Methods 0.000 description 2
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229910052623 talc Inorganic materials 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
231100000027 toxicology Toxicity 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 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
229910052905 tridymite Inorganic materials 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
210000005166 vasculature Anatomy 0.000 description 1
230000025033 vasoconstriction Effects 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
238000005550 wet granulation Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Classifications

- 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
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pain & Pain Management (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Peptides Or Proteins (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

DK198804554A 1987-08-13 1988-08-12 Indolderivater, fremgangsmåde til fremstilling deraf og farmaceutiske præparater indeholdende forbindelserne DK172696B1 (da)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
GB878719167A GB8719167D0 (en)	1987-08-13	1987-08-13	Chemical compounds
GB8719167		1987-08-13
GB8814002		1988-06-14
GB888814002A GB8814002D0 (en)	1988-06-14	1988-06-14	Chemical compounds
GB8814481		1988-06-17
GB888814481A GB8814481D0 (en)	1988-06-17	1988-06-17	Chemical compounds

Publications (3)

Publication Number	Publication Date
DK455488D0 DK455488D0 (da)	1988-08-12
DK455488A DK455488A (da)	1989-02-14
DK172696B1 true DK172696B1 (da)	1999-05-31

Family

ID=27263551

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK198804554A DK172696B1 (da)	1987-08-13	1988-08-12	Indolderivater, fremgangsmåde til fremstilling deraf og farmaceutiske præparater indeholdende forbindelserne

Country Status (28)

Country	Link
US (1)	US4997841A (fr)
EP (1)	EP0303507B1 (fr)
JP (1)	JPH0633252B2 (fr)
KR (1)	KR0131327B1 (fr)
AT (1)	ATE92057T1 (fr)
AU (1)	AU611469B2 (fr)
CA (1)	CA1310968C (fr)
CY (1)	CY1728A (fr)
CZ (1)	CZ404291A3 (fr)
DE (2)	DE3882614T2 (fr)
DK (1)	DK172696B1 (fr)
ES (1)	ES2058292T3 (fr)
FI (1)	FI92397C (fr)
GB (1)	GB2208646B (fr)
HK (1)	HK86793A (fr)
HU (1)	HU211576A9 (fr)
IE (1)	IE61488B1 (fr)
IL (1)	IL87437A0 (fr)
LU (1)	LU90160I2 (fr)
LV (1)	LV5736B4 (fr)
NL (1)	NL970035I2 (fr)
NO (2)	NO174052C (fr)
NZ (1)	NZ225820A (fr)
PH (1)	PH24976A (fr)
PT (1)	PT88255B (fr)
SG (1)	SG65393G (fr)
SK (1)	SK281495B6 (fr)
UY (1)	UY23657A1 (fr)

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GB8819024D0 (en) *	1988-08-10	1988-09-14	Glaxo Group Ltd	Chemical compounds
GB8903036D0 (en) *	1989-02-10	1989-03-30	Glaxo Group Ltd	Chemical compounds
PT97888B (pt) *	1990-06-07	1998-12-31	Zeneca Ltd	Processo para a preparacao de compostos heterociclicos derivados de indol e de composicoes farmaceuticas que os contem
DK152090D0 (da) *	1990-06-22	1990-06-22	Lundbaek A S H	Piperidylsubstituerede indolderivater
US5643784A (en) *	1990-12-04	1997-07-01	H, Lundbeck A/S	Indan derivatives
NZ243065A (en) *	1991-06-13	1995-07-26	Lundbeck & Co As H	Piperidine derivatives and pharmaceutical compositions
TW222631B (fr) *	1991-07-15	1994-04-21	Duphar Int Res
GB9209882D0 (en) *	1992-05-07	1992-06-24	Glaxo Lab Sa	Compositions
GB9211277D0 (en)	1992-05-28	1992-07-15	Glaxo Group Inc	Pharmaceutical compositions
AU675964B2 (en) *	1992-08-05	1997-02-27	John Wyeth & Brother Limited	Amide derivatives
GB9320115D0 (en) *	1993-09-29	1993-11-17	Glaxo Group Ltd	Process
US5521196A (en) *	1994-10-05	1996-05-28	Eli Lilly And Company	5-HT1F agonists for the treatment of migraine
US5521197A (en) *	1994-12-01	1996-05-28	Eli Lilly And Company	3-<1-alkylenearyl>-4-<1,2,3,6-tetrahydropyridinyl>-and 3-<1-alkylenearyl>-4-piperidinyl-1h-indoles: new 5-HT1F agonists
FR2731222A1 (fr) *	1995-03-02	1996-09-06	Pf Medicament	Nouveaux derives de piperazine aminoindoles cycliques, leur procede de preparation et leur utilisation a titre de medicaments
FR2731224B1 (fr) *	1995-03-02	1997-05-30	Pf Medicament	Nouveaux derives bi-tryptaminiques sulfonamides, leur procede de preparation et leur utilisation a titre de medicaments
NZ305166A (en) *	1995-03-20	1998-12-23	Lilly Co Eli	5-substituted-3-(1,2,3,6-tetrahydropyridin-4-yl)- and 3-(piperidin-4-yl)-1h-indoles; preparation and medicaments
AU2104097A (en) *	1996-03-13	1997-10-01	Glaxo Group Limited	Medicaments comprising 5ht1-like receptor agonists with an increased absorption
AR013669A1 (es) *	1997-10-07	2001-01-10	Smithkline Beecham Corp	Compuestos y metodos
US7189753B1 (en)	1997-11-06	2007-03-13	Cady Roger K	Preemptive prophylaxis of migraine
US6066092A (en) *	1997-11-06	2000-05-23	Cady; Roger K.	Preemptive prophylaxis of migraine device and method
UA73995C2 (en)	2000-07-21	2005-10-17	Lundbeck & Co As H	Indole derivatives being useful for the treatment of cns disorders,, a pharmaceutical composition and a method for treatment
ATE374192T1 (de) *	2000-11-29	2007-10-15	Lilly Co Eli	1-(2-m-methansulfonamidophenylethyl)-4-(m- trifluoromethylphenyl)piperazine und ihre akzeptablen pharmazeutischen salze und solvate und ihre verwendung zur behandlung von inkontinenz
US8329734B2 (en)	2009-07-27	2012-12-11	Afgin Pharma Llc	Topical therapy for migraine
EP2316468A1 (fr)	2002-02-22	2011-05-04	Shire LLC	Système de distribution et méthodes de protection et d'administration de dextroamphetamine
US20070065463A1 (en)	2003-06-20	2007-03-22	Ronald Aung-Din	Topical therapy for the treatment of migranes, muscle sprains, muscle spasms, spasticity and related conditions
AU2005309951B2 (en) *	2004-11-24	2011-07-07	Alcon, Inc.	Method of delivering nasal spray
JP2010507585A (ja) *	2006-10-19	2010-03-11	オースペックス・ファーマシューティカルズ・インコーポレイテッド	置換インドール
WO2008056378A2 (fr) *	2006-11-09	2008-05-15	Natco Pharma Limited	Nouveau procédé destiné à la préparation de naratriptan
WO2008072257A2 (fr) *	2006-12-12	2008-06-19	Ind-Swift Laboratories Limited	Procédé de préparation de dérivés de l'indole
WO2009016466A2 (fr) *	2007-07-30	2009-02-05	Orchid Chemicals & Pharmaceuticals Limited	Procédé de préparation de chlorhydrate de naratriptan
WO2009118753A2 (fr) *	2008-03-07	2009-10-01	Usv Limited	Procédé de préparation de chlorhydrate de naratriptane
US8592424B2 (en)	2008-06-30	2013-11-26	Afgin Pharma Llc	Topical regional neuro-affective therapy
WO2010004580A2 (fr) *	2008-07-11	2010-01-14	Ind-Swift Laboratories Limited	Procédé de préparation de dérivés d'indole
WO2010084507A2 (fr) *	2008-07-15	2010-07-29	Sun Pharmaceutical Industries Ltd.	Procédé de synthèse du n-méthyl-2-[3-(1-méthyl-4-pipéridyl)-1h-indol-5-yl]-éthanesulfonamide et de ses sels d'addition acide
NZ597620A (en)	2009-08-20	2013-08-30	Cipla Ltd	A process for the synthesis of naratriptan
CN102276581B (zh) *	2011-08-05	2013-06-12	上海师范大学	N-取代四氢吡啶连吲哚类化合物及其制备方法及应用
US10383816B2 (en)	2015-03-02	2019-08-20	Afgin Pharma, Llc	Topical regional neuro-affective therapy with cannabinoid combination products
HK1244715A1 (zh)	2015-03-02	2018-08-17	阿福金制药有限责任公司	用大麻素的局部区域神经影响性疗法
US20180049994A1 (en)	2016-08-16	2018-02-22	Afgin Pharma, Llc	Topical regional neuro-affective therapy with caryophyllene
EP3766483A1 (fr)	2019-07-19	2021-01-20	BioPharma Synergies, S. L.	Composition de poudre orodispersible comprenant un triptane

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FR2362628A1 (fr) *	1976-08-26	1978-03-24	Roussel Uclaf	Nouveaux derives du piperidyl-indole et leurs sels, procede de preparation et application a titre de medicaments
FR2421899A1 (fr) *	1978-01-16	1979-11-02	Roussel Uclaf	Nouveaux derives du tetrahydropyridinyl-indole et leurs sels, le procede de preparation et l'application a titre de medicaments de ces nouveaux produits
IT1170387B (it) *	1982-06-07	1987-06-03	Glaxo Group Ltd	Composti eterociclici, procedimento per prepararli e composizioni farmaceutiche che li contengono
FR2533924A1 (fr) *	1982-10-05	1984-04-06	Roussel Uclaf	Nouveaux derives du 4-(1h-indol-3-yl)a-methyl piperidine-1-ethanol, leurs sels, le procede de preparation, l'application a titre de medicaments et les compositions les renfermant
GB8332437D0 (en) *	1983-12-06	1984-01-11	Glaxo Group Ltd	Chemical compounds
HU196752B (en) *	1983-12-06	1989-01-30	Glaxo Group Ltd	Process for production of medical compositions containing indole-derivatives and these compounds
DE3419935A1 (de) *	1984-05-28	1985-11-28	Merck Patent Gmbh, 6100 Darmstadt	Verwendung von hydroxyindolderivaten bei der senkung des blutdrucks
GB2162522B (en) *	1984-08-01	1988-02-24	Glaxo Group Ltd	An indole derivative
US4548939A (en) *	1984-10-01	1985-10-22	Janssen Pharmaceutica N. V.	1H-Indol-3-yl containing 1,3-dimethyl-1H-purine-2,6-diones
IT1181741B (it) *	1984-12-04	1987-09-30	Glaxo Group Ltd	Derivati di indolo,procedimento per prepararli e composizioni farmaceutiche che li contengono
IE58370B1 (en) *	1985-04-10	1993-09-08	Lundbeck & Co As H	Indole derivatives
GB8819024D0 (en) *	1988-08-10	1988-09-14	Glaxo Group Ltd	Chemical compounds
GB8903036D0 (en) *	1989-02-10	1989-03-30	Glaxo Group Ltd	Chemical compounds

1988
- 1988-08-12 EP EP88307499A patent/EP0303507B1/fr not_active Expired - Lifetime
- 1988-08-12 DK DK198804554A patent/DK172696B1/da not_active IP Right Cessation
- 1988-08-12 JP JP63201839A patent/JPH0633252B2/ja not_active Expired - Lifetime
- 1988-08-12 AU AU20692/88A patent/AU611469B2/en not_active Expired
- 1988-08-12 KR KR88010367A patent/KR0131327B1/ko not_active Expired - Lifetime
- 1988-08-12 ES ES88307499T patent/ES2058292T3/es not_active Expired - Lifetime
- 1988-08-12 FI FI883744A patent/FI92397C/fi not_active IP Right Cessation
- 1988-08-12 PH PH37409A patent/PH24976A/en unknown
- 1988-08-12 IL IL87437A patent/IL87437A0/xx not_active IP Right Cessation
- 1988-08-12 US US07/231,274 patent/US4997841A/en not_active Expired - Lifetime
- 1988-08-12 CA CA000574643A patent/CA1310968C/fr not_active Expired - Lifetime
- 1988-08-12 PT PT88255A patent/PT88255B/pt not_active IP Right Cessation
- 1988-08-12 DE DE88307499T patent/DE3882614T2/de not_active Expired - Lifetime
- 1988-08-12 NZ NZ225820A patent/NZ225820A/xx unknown
- 1988-08-12 IE IE247788A patent/IE61488B1/en not_active IP Right Cessation
- 1988-08-12 GB GB8819200A patent/GB2208646B/en not_active Expired - Lifetime
- 1988-08-12 NO NO883587A patent/NO174052C/no not_active IP Right Cessation
- 1988-08-12 AT AT88307499T patent/ATE92057T1/de active
- 1988-08-13 SK SK4042-91A patent/SK281495B6/sk unknown
1991
- 1991-12-23 CZ CS914042A patent/CZ404291A3/cs unknown
1993
- 1993-05-19 SG SG653/93A patent/SG65393G/en unknown
- 1993-08-19 HK HK867/93A patent/HK86793A/xx not_active IP Right Cessation
- 1993-09-23 UY UY23657A patent/UY23657A1/es not_active IP Right Cessation
1994
- 1994-05-06 CY CY172894A patent/CY1728A/en unknown
1995
- 1995-06-30 HU HU95P/P00631P patent/HU211576A9/hu unknown
- 1995-12-14 LV LV950371A patent/LV5736B4/xx unknown
1997
- 1997-09-10 NL NL970035C patent/NL970035I2/nl unknown
- 1997-10-31 LU LU90160C patent/LU90160I2/fr unknown
1998
- 1998-02-05 NO NO1998008C patent/NO1998008I1/no unknown
- 1998-08-12 DE DE19983883614 patent/DE19775082I2/de active Active

Also Published As

Publication number	Publication date
NL970035I1 (nl)	1997-11-03
FI883744L (fi)	1989-02-14
CZ404291A3 (en)	1993-04-14
KR890003731A (ko)	1989-04-17
PH24976A (en)	1990-12-26
IE61488B1 (en)	1994-11-02
EP0303507B1 (fr)	1993-07-28
DK455488D0 (da)	1988-08-12
CY1728A (en)	1994-05-06
EP0303507A3 (en)	1990-09-19
IL87437A0 (en)	1989-01-31
US4997841A (en)	1991-03-05
PT88255A (pt)	1989-06-30
LV5736A4 (lv)	1996-06-20
IE882477L (en)	1989-02-13
CA1310968C (fr)	1992-12-01
GB8819200D0 (en)	1988-09-14
FI883744A0 (fi)	1988-08-12
KR0131327B1 (en)	1998-04-17
NO174052C (no)	1994-03-09
GB2208646A (en)	1989-04-12
GB2208646B (en)	1991-06-26
NL970035I2 (nl)	1998-01-05
HK86793A (en)	1993-08-27
PT88255B (pt)	1995-03-01
AU611469B2 (en)	1991-06-13
ATE92057T1 (de)	1993-08-15
LV5736B4 (lv)	1997-06-20
LU90160I2 (fr)	1998-01-14
DE19775082I2 (de)	2006-04-27
NO174052B (no)	1993-11-29
NZ225820A (en)	1990-09-26
DK455488A (da)	1989-02-14
AU2069288A (en)	1989-02-16
EP0303507A2 (fr)	1989-02-15
DE3882614D1 (de)	1993-09-02
UY23657A1 (es)	1994-02-25
FI92397C (fi)	1994-11-10
SG65393G (en)	1993-08-06
JPH0633252B2 (ja)	1994-05-02
SK404291A3 (en)	2000-09-12
SK281495B6 (sk)	2001-04-09
FI92397B (fi)	1994-07-29
DE3882614T2 (de)	1993-11-18
NO883587L (no)	1989-02-14
JPH01207288A (ja)	1989-08-21
NO883587D0 (no)	1988-08-12
HU211576A9 (en)	1995-12-28
NO1998008I1 (no)	1998-02-05
ES2058292T3 (es)	1994-11-01

Legal Events

Date	Code	Title	Description
1999-05-31	B1	Patent granted (law 1993)
2008-09-01	PUP	Patent expired

Publication	Publication Date	Title
DK172696B1 (da)	1999-05-31	Indolderivater, fremgangsmåde til fremstilling deraf og farmaceutiske præparater indeholdende forbindelserne
JP2941309B2 (ja)	1999-08-25	化合物
US4816470A (en)	1989-03-28	Heterocyclic compounds
CZ150596A3 (en)	1997-05-14	Tetrahydrocarbazole derivatives, process of their preparation and pharmaceutical compositions containing thereof
EP0303506A2 (fr)	1989-02-15	Dérivés d'indole
DK158942B (da)	1990-08-06	3-(2-(dimethylamino)ethyl)-n-methyl-1h-indol-5-methansulfonamid, farmaceutiske praeparater indeholdende denne forbindelse samt fremgangsmaader til fremstilling af forbindelsen
JPH05507288A (ja)	1993-10-21	インドール誘導体
SK404491A3 (en)	2000-12-11	Tricyclic lactam compounds, pharmaceutical compositions comprising same and their use
KR20040103973A (ko)	2004-12-09	Ｎ-[페닐(피페리딘-2-일)메틸]벤즈아미드의 유도체, 그의제조 방법 및 치료법에서의 그의 용도
KR0183396B1 (ko)	1999-05-01	3-아릴카르보닐-1-아미노알킬-1h-인돌류,이를 함유하는 항녹내장 조성물 및 이의 제조방법
FR2574793A1 (fr)	1986-06-20	Composes derives d'indole, compositions pharmaceutiques les contenant et procede pour leur preparation
PT94070A (pt)	1991-01-08	Processo para a preparacao de derivados de piperazina
EP0382570B1 (fr)	1993-12-08	Dérivés de l'indole
EP0104632A2 (fr)	1984-04-04	1'-(3-(1,2-Benzisoxazol-3-yl)propyl)spiro-(benzofuran-2-(3H),3'- ou 4'-pipéridines ou 3'-pyrrolidines), procédé pour leur préparation et leur utilisation comme médicaments
JP3174158B2 (ja)	2001-06-11	６−オキソ−アゼピノインドール化合物、該化合物を含有する、胃の運動機能を調整する作用を有する医薬品および抗偏頭痛作用するセロトニン拮抗作用を有する医薬品並びに該化合物を製造する方法および該化合物を製造するための中間生成物
JP2941702B2 (ja)	1999-08-30	５‐ｈｔ３レセプターにおいて５‐ｈｔの作用に拮抗するラクタム誘導体を含む医薬組成物
EP0746556B1 (fr)	2002-09-25	Composes tricycliques ayant une affinite pour le recepteur de 5-ht1a
WO2006115245A1 (fr)	2006-11-02	Dérivé de 4-éthynylisoquinoléine et préparation pharmaceutique comprenant celui-ci
HU202225B (en)	1991-02-28	Process for producing indole derivatives