DK171079B1 - Indoloquinonforbindelser og fremgangsmåder til deres fremstilling samt lægemiddel med indhold deraf - Google Patents

Indoloquinonforbindelser og fremgangsmåder til deres fremstilling samt lægemiddel med indhold deraf Download PDF

Info

Publication number: DK171079B1
Authority: DK; Denmark
Prior art keywords: group; compound; methyl; methoxy; indole
Prior art date: 1986-04-17

Application number

DK659887A

Other languages

Danish (da)

English (en)

Other versions

DK659887A (da

DK659887D0 (da

Inventor

Everardus Arnoldus Oostveen

Willem Nico Speckamp

Original Assignee

Everardus Arnoldus Oostveen

Willem Nico Speckamp

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.)

1986-04-17

Filing date

1987-12-16

Publication date

1996-05-28

1986-04-17 Priority claimed from GB868609369A external-priority patent/GB8609369D0/en

1986-06-24 Priority claimed from GB868615383A external-priority patent/GB8615383D0/en

1986-12-04 Priority claimed from GB868629049A external-priority patent/GB8629049D0/en

1987-12-16 Application filed by Everardus Arnoldus Oostveen, Willem Nico Speckamp filed Critical Everardus Arnoldus Oostveen

1987-12-16 Publication of DK659887D0 publication Critical patent/DK659887D0/da

1988-02-15 Publication of DK659887A publication Critical patent/DK659887A/da

1996-05-28 Application granted granted Critical

1996-05-28 Publication of DK171079B1 publication Critical patent/DK171079B1/da

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 94
238000000034 method Methods 0.000 title claims abstract description 30
238000002360 preparation method Methods 0.000 title claims description 12
239000003814 drug Substances 0.000 title claims description 11
229940079593 drug Drugs 0.000 title claims description 10
125000000217 alkyl group Chemical group 0.000 claims abstract description 22
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
239000001257 hydrogen Substances 0.000 claims abstract description 20
125000003277 amino group Chemical group 0.000 claims abstract description 9
239000000824 cytostatic agent Substances 0.000 claims abstract description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 8
229910052736 halogen Inorganic materials 0.000 claims abstract description 6
150000002367 halogens Chemical class 0.000 claims abstract description 6
229910021645 metal ion Inorganic materials 0.000 claims abstract description 5
125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
150000002431 hydrogen Chemical class 0.000 claims abstract 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract 8
125000004414 alkyl thio group Chemical group 0.000 claims abstract 2
238000004519 manufacturing process Methods 0.000 claims abstract 2
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 121
JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 claims description 80
-1 4-hydroxy-piperidino group Chemical group 0.000 claims description 39
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
238000003818 flash chromatography Methods 0.000 claims description 28
238000006243 chemical reaction Methods 0.000 claims description 25
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 24
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 21
LCPQHPZPSPNDSA-UHFFFAOYSA-N 3-chloro-4-nitrosophenol Chemical compound OC1=CC=C(N=O)C(Cl)=C1 LCPQHPZPSPNDSA-UHFFFAOYSA-N 0.000 claims description 17
230000008569 process Effects 0.000 claims description 15
239000000047 product Substances 0.000 claims description 14
238000000746 purification Methods 0.000 claims description 11
HORNXRXVQWOLPJ-UHFFFAOYSA-N 3-chlorophenol Chemical compound OC1=CC=CC(Cl)=C1 HORNXRXVQWOLPJ-UHFFFAOYSA-N 0.000 claims description 9
FSGQCPBSYXOZGV-UHFFFAOYSA-N methyl 5-methoxy-2-(3-methoxy-3-oxoprop-1-enyl)-1-methyl-4,7-dioxoindole-3-carboxylate Chemical compound CN1C(C=CC(=O)OC)=C(C(=O)OC)C2=C1C(=O)C=C(OC)C2=O FSGQCPBSYXOZGV-UHFFFAOYSA-N 0.000 claims description 8
ZZPNFQZMDUFJLD-UHFFFAOYSA-N 1-acetyl-2-(2-carboxyethenyl)-5-methoxy-2,3-dihydroindole-3-carboxylic acid Chemical compound COC1=CC=C2N(C(C)=O)C(C=CC(O)=O)C(C(O)=O)C2=C1 ZZPNFQZMDUFJLD-UHFFFAOYSA-N 0.000 claims description 7
QTIDRIQSPAELJC-UHFFFAOYSA-N 2-chloro-4-methoxy-1-nitrobenzene Chemical compound COC1=CC=C([N+]([O-])=O)C(Cl)=C1 QTIDRIQSPAELJC-UHFFFAOYSA-N 0.000 claims description 7
DKTRZBWXGOPYIX-UHFFFAOYSA-N 3-chloro-4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C(Cl)=C1 DKTRZBWXGOPYIX-UHFFFAOYSA-N 0.000 claims description 7
150000002475 indoles Chemical class 0.000 claims description 7
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 6
FQNAAAKQGJUSRG-UHFFFAOYSA-N diethyl 5-methoxy-2-(3-methoxy-3-oxoprop-1-enyl)-1,2-dihydroindole-3,3-dicarboxylate Chemical compound C1=C(OC)C=C2C(C(=O)OCC)(C(=O)OCC)C(C=CC(=O)OC)NC2=C1 FQNAAAKQGJUSRG-UHFFFAOYSA-N 0.000 claims description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 5
150000002466 imines Chemical class 0.000 claims description 5
IRVXUZCIGJYJHC-UHFFFAOYSA-N methyl 5-methoxy-2-(3-methoxy-3-oxoprop-1-enyl)-1-methyl-4-nitroindole-3-carboxylate Chemical compound COC1=CC=C2N(C)C(C=CC(=O)OC)=C(C(=O)OC)C2=C1[N+]([O-])=O IRVXUZCIGJYJHC-UHFFFAOYSA-N 0.000 claims description 5
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238000007254 oxidation reaction Methods 0.000 claims description 5
150000001412 amines Chemical class 0.000 claims description 4
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125000000524 functional group Chemical group 0.000 claims description 4
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 3
238000010531 catalytic reduction reaction Methods 0.000 claims description 3
238000009833 condensation Methods 0.000 claims description 3
230000005494 condensation Effects 0.000 claims description 3
230000009935 nitrosation Effects 0.000 claims description 3
238000007034 nitrosation reaction Methods 0.000 claims description 3
CFKLDVQMQBYPIZ-UHFFFAOYSA-N 2-(2-amino-3,4-diethyl-5-methoxyphenyl)propanedioic acid Chemical compound CCC1=C(C=C(C(=C1CC)N)C(C(=O)O)C(=O)O)OC CFKLDVQMQBYPIZ-UHFFFAOYSA-N 0.000 claims description 2
229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 2
229910021529 ammonia Inorganic materials 0.000 claims description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
LADGKXJCKVKXAP-UHFFFAOYSA-N ethyl 2-cyano-2-(5-methoxy-2-nitrophenyl)acetate Chemical compound CCOC(=O)C(C#N)C1=CC(OC)=CC=C1[N+]([O-])=O LADGKXJCKVKXAP-UHFFFAOYSA-N 0.000 claims description 2
RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
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230000020477 pH reduction Effects 0.000 claims description 2
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 claims description 2
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230000004048 modification Effects 0.000 claims 2
238000012986 modification Methods 0.000 claims 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 claims 1
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 1
125000003047 N-acetyl group Chemical group 0.000 claims 1
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229940125773 compound 10 Drugs 0.000 claims 1
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239000012467 final product Substances 0.000 claims 1
ZTQSADJAYQOCDD-UHFFFAOYSA-N ginsenoside-Rd2 Natural products C1CC(C2(CCC3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC1OCC(O)C(O)C1O ZTQSADJAYQOCDD-UHFFFAOYSA-N 0.000 claims 1
150000004820 halides Chemical class 0.000 claims 1
ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims 1
238000006396 nitration reaction Methods 0.000 claims 1
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150000003839 salts Chemical class 0.000 claims 1
125000003118 aryl group Chemical group 0.000 abstract description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 2
150000001720 carbohydrates Chemical group 0.000 abstract 2
125000005110 aryl thio group Chemical group 0.000 abstract 1
125000004104 aryloxy group Chemical group 0.000 abstract 1
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 abstract 1
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239000002609 medium Substances 0.000 description 6
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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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- 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
- C07D209/12—Radicals substituted by oxygen atoms
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
General Chemical & Material Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Saccharide Compounds (AREA)
Indole Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Polysaccharides And Polysaccharide Derivatives (AREA)

DK659887A 1986-04-17 1987-12-16 Indoloquinonforbindelser og fremgangsmåder til deres fremstilling samt lægemiddel med indhold deraf DK171079B1 (da)

Applications Claiming Priority (8)

Application Number	Priority Date	Filing Date	Title
GB8609369		1986-04-17
GB868609369A GB8609369D0 (en)	1986-04-17	1986-04-17	Indoloquinone compounds
GB8615383		1986-06-24
GB868615383A GB8615383D0 (en)	1986-06-24	1986-06-24	Pathways to bioactive indoletype compounds
GB8629049		1986-12-04
GB868629049A GB8629049D0 (en)	1986-12-04	1986-12-04	Indoloquinone compounds
PCT/GB1987/000253 WO1987006227A2 (fr)	1986-04-17	1987-04-15	Composes d'indoloquinone
GB8700253		1987-04-15

Publications (3)

Publication Number	Publication Date
DK659887D0 DK659887D0 (da)	1987-12-16
DK659887A DK659887A (da)	1988-02-15
DK171079B1 true DK171079B1 (da)	1996-05-28

Family

ID=27262993

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK659887A DK171079B1 (da)	1986-04-17	1987-12-16	Indoloquinonforbindelser og fremgangsmåder til deres fremstilling samt lægemiddel med indhold deraf

Country Status (8)

Country	Link
US (1)	US5079257A (fr)
EP (1)	EP0302874B1 (fr)
JP (1)	JPH0819095B2 (fr)
AT (1)	ATE82961T1 (fr)
AU (1)	AU615877B2 (fr)
DE (1)	DE3782938T2 (fr)
DK (1)	DK171079B1 (fr)
WO (1)	WO1987006227A2 (fr)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1990008135A1 (fr) *	1989-01-12	1990-07-26	Vsesojuzny Nauchno-Issledovatelsky Khimiko-Farmatsevtichesky Institut Imeni S.Ordzhonikidze (Vnikhfi)	Monohydrate d'hydrochlorure d'acide ethyle ester 6-brome-5-hydroxy-4-dimethyle-aminomethyle-1-methyle-2-phenylthiomethyle indole-3-carboxylique, son procede d'obtention et preparation pharmaceutique presentant une activite antivirale, de stimulation d'interferon et d'immunomodulation basee sur ledit compose
JPH0616628A (ja) *	1992-04-07	1994-01-25	Kyowa Hakko Kogyo Co Ltd	インドール誘導体
WO1997023456A1 (fr) *	1995-12-21	1997-07-03	British Technology Group Ltd.	Derives d'indoloquinone utilises comme agents bioreducteurs
ATE493126T1 (de) *	2001-11-01	2011-01-15	Spectrum Pharmaceuticals Inc	Medizinische zusammensetzungen zur intravesikalen behandlung von blasenkrebs
US8563592B2 (en)	2001-11-01	2013-10-22	Spectrum Pharmaceuticals, Inc.	Bladder cancer treatment and methods
CA2516078C (fr) *	2003-02-28	2014-04-29	Oxigene, Inc.	Compositions de catechol et leur utilisation
AU2006230582A1 (en) *	2005-03-31	2006-10-05	Spectrum Pharmaceuticals, Inc.	Indoloquinone tumor radiation sensitization
WO2014062856A1 (fr)	2012-10-16	2014-04-24	Halozyme, Inc.	Hypoxie et hyaluronane et leurs marqueurs pour le diagnostic et la surveillance de maladies et de pathologies, et méthodes associées

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3215705A (en) *	1963-10-11	1965-11-02	American Cyanamid Co	4-amino-3-hydroxymethyl indole derivatives
US3265698A (en) *	1964-08-07	1966-08-09	American Cyanamid Co	Novel substituted 3-(alpha-carbamoyloxy-lower alkyl)-4, 7-indoloquinones

1987
- 1987-04-15 WO PCT/GB1987/000253 patent/WO1987006227A2/fr not_active Ceased
- 1987-04-15 AU AU72361/87A patent/AU615877B2/en not_active Ceased
- 1987-04-15 EP EP87902608A patent/EP0302874B1/fr not_active Expired - Lifetime
- 1987-04-15 AT AT87902608T patent/ATE82961T1/de not_active IP Right Cessation
- 1987-04-15 US US07/278,531 patent/US5079257A/en not_active Expired - Lifetime
- 1987-04-15 JP JP62502324A patent/JPH0819095B2/ja not_active Expired - Fee Related
- 1987-04-15 DE DE87902608T patent/DE3782938T2/de not_active Expired - Fee Related
- 1987-12-16 DK DK659887A patent/DK171079B1/da not_active IP Right Cessation

Also Published As

Publication number	Publication date
EP0302874A1 (fr)	1989-02-15
WO1987006227A3 (fr)	1988-01-28
JPH01502906A (ja)	1989-10-05
US5079257A (en)	1992-01-07
EP0302874B1 (fr)	1992-12-02
AU615877B2 (en)	1991-10-17
DK659887A (da)	1988-02-15
WO1987006227A2 (fr)	1987-10-22
DE3782938D1 (de)	1993-01-14
ATE82961T1 (de)	1992-12-15
JPH0819095B2 (ja)	1996-02-28
DE3782938T2 (de)	1993-10-21
DK659887D0 (da)	1987-12-16
AU7236187A (en)	1987-11-09

Legal Events

Date	Code	Title	Description
2006-12-04	PBP	Patent lapsed	Country of ref document: DK

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