EP0662960A1 - Neue asymmetrisch substituierte bis-naphthalimide - Google Patents

Neue asymmetrisch substituierte bis-naphthalimide

Info

Publication number
EP0662960A1
EP0662960A1 EP93920807A EP93920807A EP0662960A1 EP 0662960 A1 EP0662960 A1 EP 0662960A1 EP 93920807 A EP93920807 A EP 93920807A EP 93920807 A EP93920807 A EP 93920807A EP 0662960 A1 EP0662960 A1 EP 0662960A1
Authority
EP
European Patent Office
Prior art keywords
groups
alkyl
different
acid
formula
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP93920807A
Other languages
German (de)
English (en)
French (fr)
Inventor
Miguel Fernandez Brana
José Maria CASTELLANO BERLANGA
Marina Moran Moset
Maria Jesús PEREZ DE VEGA
Gerhard Keilhauer
Xiao-Dong Qian
Cynthia Romerdahl
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Abbott GmbH and Co KG
Original Assignee
Knoll GmbH
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.)
Filing date
Publication date
Application filed by Knoll GmbH filed Critical Knoll GmbH
Publication of EP0662960A1 publication Critical patent/EP0662960A1/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/04—Ortho- or peri-condensed ring systems
    • C07D221/18—Ring systems of four or more rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to new asymmetrically substituted bis-naphthalimides, their preparation and their use in combating diseases.
  • the invention relates to asymmetrically substituted bis-naphthalimides of the formula I.
  • A, B and D are identical or different and denote straight or branched chain alkylidene groups, cycloalkylidene or phenylene radicals,
  • R 1 and R 2 are the same or different and are hydrogen atoms or C 6 alkyl, or aryl or benzyl groups, which are C 6 alkyl groups, halogen atoms, CF,
  • CONHR 7 -, HCOR 8 -, S0 2 NHR 9 - or SO m R 10 group may be substituted, mean, or together represent a -CH 2 -, - 2 H 4 - or -C 3 H 6 group ,
  • X, X ', Y and Y' are the same or different and are hydrogen or halogen atoms, nitro, amino, Ci-g-alkyl, CF 3 -,
  • preferred alkylidene groups are those with 1-8 and in particular those with 1-4 C atoms.
  • Preferred cycloalkylidene radicals are those having 3 to 7 carbon atoms.
  • Phenyl groups in particular can be mentioned as aryl groups for R 1 -R 8 .
  • the latter are preferably substituted by 1-2 of the radicals mentioned.
  • Preferred cycloalkyl radicals for R 3 - R 11 are those with 3 - 7 C atoms.
  • X and Y are preferably nitro, amino or methyl groups or chlorine atoms and X 'and Y' are preferably hydrogen.
  • the new compounds can be prepared according to the following reaction scheme:
  • Naphthic acid anhydrides II are reacted with an equivalent or with an excess of up to 50% of a polyamine III in an organic solvent such as dioxane, ethanol or dimethylformamide at 20 to 150 ° C.
  • the solution thus obtained is concentrated and the residue is purified, for example by recrystallization or chromatography.
  • the monoimide thus obtained is then reacted with the anhydride V as described above and purified.
  • the compounds thus obtained can then, if desired, be converted into their salts with physiologically tolerated acids.
  • the bases are taken up, for example, in ethanol, dichloromethane or ether and the salt is precipitated with the acid.
  • Suitable acids are citric acid, tartaric acid, lactic acid, phosphoric acid, alkanesulfonic acids, especially methanesulfonic acid, acetic acid, formic acid, maleic acid, fumaric acid, malic acid, succinic acid, malonic acid, sulfuric acid, toluenesulfonic acid, L-glutamic acid, L-aspartic acid, pyruvic acid , Benzoic acid, glucuronic acid, oxalic acid, ascorbic acid and especially hydrochloric acid.
  • the starting materials of the formula V with a single bond in a five-membered ring can be prepared by processes known in the literature (J. Amer. Chem. Soc. 93, 737 (1971)).
  • the corresponding compounds with a double bond in the five-membered ring are obtained from those with a single bond according to the method described in J. Amer. Chem. Soc. 91, 917 (1969) for pyracycloquinones.
  • the polyamines III are commercially available or can be prepared by known processes.
  • the new compounds activate non-specific immune cells that kill tumor cells. They can therefore be used for cancer diseases such as colon, lung and breast cancer as well as leukemia. Your application dose is about 1 - 500 mg / kg body weight.
  • the new compounds have the advantage of good solubility in water. They are therefore much easier to use than the known compounds with a similar structure.

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Indole Compounds (AREA)
EP93920807A 1992-09-30 1993-09-23 Neue asymmetrisch substituierte bis-naphthalimide Withdrawn EP0662960A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE4232739 1992-09-30
DE4232739A DE4232739A1 (de) 1992-09-30 1992-09-30 Neue asymmetrisch substituierte bis-Naphthalimide
PCT/EP1993/002581 WO1994007862A1 (de) 1992-09-30 1993-09-23 Neue asymmetrisch substituierte bis-naphthalimide

Publications (1)

Publication Number Publication Date
EP0662960A1 true EP0662960A1 (de) 1995-07-19

Family

ID=6469201

Family Applications (1)

Application Number Title Priority Date Filing Date
EP93920807A Withdrawn EP0662960A1 (de) 1992-09-30 1993-09-23 Neue asymmetrisch substituierte bis-naphthalimide

Country Status (9)

Country Link
US (1) US5554622A (zh)
EP (1) EP0662960A1 (zh)
JP (1) JPH08502050A (zh)
CN (1) CN1094036A (zh)
CA (1) CA2145867A1 (zh)
DE (1) DE4232739A1 (zh)
MX (1) MX9306035A (zh)
TW (1) TW272191B (zh)
WO (1) WO1994007862A1 (zh)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5461176A (en) * 1991-03-27 1995-10-24 The Du Pont Merck Pharmaceutical Company Processes for preparing bis-naphthalimides containing amino-acid derived linkers
US5359070A (en) * 1993-02-11 1994-10-25 The Du Pont Merck Pharmaceutical Company Unsymmetrical bis-imides as anticancer agents
IL110460A (en) * 1993-08-18 2001-01-11 Basf Ag Bite-naphthalimides, their preparation and pharmaceutical preparations containing them
WO1995029895A1 (en) * 1994-04-28 1995-11-09 Knoll Aktiengesellschaft Dihydrodibenzo(de,h)isoquinolines derivatives and their use as anti-cancer agents
US5703089A (en) * 1994-04-28 1997-12-30 Knoll Aktiengesellschaft Dihydrodibenzisoquinolinediones
DK0930883T3 (da) * 1996-10-21 2006-05-22 Nps Allelix Corp Neurotrofinantagonister til behandling af epilepsi, Alzheimers sygdom og smerte
US6468990B1 (en) * 1999-05-17 2002-10-22 Queen's University At Kingston Method of inhibiting binding of nerve growth factor to p75 NTR receptor
US6492380B1 (en) * 1999-05-17 2002-12-10 Queen's University At Kingston Method of inhibiting neurotrophin-receptor binding
JP2007536283A (ja) * 2004-05-05 2007-12-13 ユニバイオスクリーン エス．アー． ナフタルイミド誘導体、それらの製造方法、およびそれらの医薬組成物
JP4638485B2 (ja) * 2004-06-30 2011-02-23 カウンシル オブ サイエンティフィク アンド インダストリアル リサーチ ピペラジン部分により結合したピロロ［２，１−ｃ］［１，４］ベンゾジアゼピン−ナフタルイミド結合体及びそれを調製するための方法
US6979684B1 (en) 2004-06-30 2005-12-27 Council Of Scientific And Industrial Research Pyrrolo[2,1-c][1,4]benzodiazepine-napthalimide conjugates linked through piperazine moiety and process for preparation thereof
EP1931664A4 (en) 2005-09-15 2010-12-08 Painceptor Pharma Corp PROCESS FOR MODULATING NEUROTROPHINE-MEDIATED ACTIVITY
PT103503B (pt) 2006-06-19 2009-05-18 Univ Do Porto Novos derivados do bisnaftalimidopropil, processo para a sua preparação, composições farmacêuticas que os contêm e sua utilização em doenças cancerígenas e parasitárias, nomeadamente leishmanioses, tripanossomíases e malária.

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3604827A1 (de) * 1986-02-15 1987-08-20 Bayer Ag Elektrophotographische toner
DE3707651A1 (de) * 1987-03-10 1988-09-22 Knoll Ag Bis-naphthalimide, ihre herstellung und verwendung
US5086059A (en) * 1990-06-07 1992-02-04 Du Pont Merck Pharmaceutical Company Bis-naphthalimides as anticancer agents
US5359070A (en) * 1993-02-11 1994-10-25 The Du Pont Merck Pharmaceutical Company Unsymmetrical bis-imides as anticancer agents

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9407862A1 *

Also Published As

Publication number Publication date
TW272191B (en) 1996-03-11
US5554622A (en) 1996-09-10
DE4232739A1 (de) 1994-03-31
MX188885B (zh) 1998-05-12
WO1994007862A1 (de) 1994-04-14
MX9306035A (es) 1994-05-31
JPH08502050A (ja) 1996-03-05
CA2145867A1 (en) 1994-04-14
CN1094036A (zh) 1994-10-26

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