EP0142543A1 - Azidirino derivatives of tetrameric cyclophosphazenes - Google Patents

Azidirino derivatives of tetrameric cyclophosphazenes

Info

Publication number
EP0142543A1
EP0142543A1 EP84902089A EP84902089A EP0142543A1 EP 0142543 A1 EP0142543 A1 EP 0142543A1 EP 84902089 A EP84902089 A EP 84902089A EP 84902089 A EP84902089 A EP 84902089A EP 0142543 A1 EP0142543 A1 EP 0142543A1
Authority
EP
European Patent Office
Prior art keywords
aziridino
compound
formula
tetrameric
derivative
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Withdrawn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
EP84902089A
Other languages
German (de)
English (en)
French (fr)
Inventor
Johan Christoph Van De Grampel
Adriaan Albert Van Der Huizen
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.)
Rijksuniversiteit Groningen
Original Assignee
Rijksuniversiteit Groningen
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 Rijksuniversiteit Groningen filed Critical Rijksuniversiteit Groningen
Publication of EP0142543A1 publication Critical patent/EP0142543A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/65812—Cyclic phosphazenes [P=N-]n, n>=3
    • C07F9/65817—Cyclic phosphazenes [P=N-]n, n>=3 n = 4

Definitions

  • the invention relates to an aziridino derivative of a tetrameric cyclochlorophosphazene compound.
  • the (NPCL 2 ) -tetramer having the formula N 4 P 4 Cl 8 and the compound N 4 P 4 Az 8 derived therefrom, in which Az is aziridino, are known from the article by V.A. Chernov, V.B. Lytkina, S.I. Sergievskaya, A.A. Kropacheva, V.A. Parshina and L.E. Sventsitskaya, Farmakol. Toksikol. (Moscow) 22, 365 (1959). Of the compound N 4 P 4 Az 8 it is indicated that it has an anti-tumor activity with respect to S-45 sarcoma in rats. Moreover, Inorg. Chem.
  • N 4 P 4 Az 8 can be prepared by complete aminolysis of the tetrameric N 4 P 4 Cl 8 by means of aziridine or a homologue thereof in an aromatic hydrocarbon as reaction medium and triethylamine as acid acceptor. It is an object of the invention to provide an aziridino derivative of a tetrameric cyclochlorophosphazene compound which may serve as starting-material in the synthesis of tetrameric cyclophosphazene compounds to be derived therefrom and containing one or more aziridino groups by substitution of the chlorine atoms by a properly selected substituent, of which latter compounds it may be expected that they also have an anti-tumor activity.
  • the ratio of mono-aziri- dino to polyaziridino substitution is, e.g. in the case of starting from (NPCL 2 ) 4 ,the ratio in the reaction product of mono-aziridino to di-aziridino substitution, to be varied by affecting the molar ratio of the reaction components and, if required, the reaction time.
  • a suitable solvent in which the process according to the invention can be carried out is dry diethyl ether but also benzene, pentane, hexane and THF (tetrahydrofuran) are suitable for having reactions carried out therein.
  • the aziridino derivative of the tetrameric cyclochlorophosphazene compounds according to the invention are suitable starting materials for preparing compounds therefrom, the chlorine atoms being replaced by properly selected other substituents.
  • the chlorine atoms being replaced by properly selected other substituents.
  • it may be expected that such compounds have an anti-tumor activity.
  • R is an electron donating group of low sensitivity to hydrolysis.
  • the invention will be illustrated by the example given herein below.
  • NPCL 2 (Otsuka Chem.) was recrystaliized from hexane before use.
  • Aziridine was distilled from KOH pills under dry nitrogen just before use.
  • Solvents were purified and dried in the conventional manner. Reactions were carried out under a dry nitrogen atmosphere.
  • 31 P and 1 H NMR spectra were measured with a Nicolet 283A FT spectrometer equipped with an NTCFT1180 data system, in 10 mm tubes at 25°C.
  • the deuterium resonance of the solvent (CDCl 3 ) was used as "field-frequency lock”.
  • HPLC separations were carried out by using two Waters 6000A liquid pumps (each having a capacity of 20 cm 3 /min.) and a Waters R401 refractometer. Lichrosorb Si 60/10 served as column material.
  • fraction 5 consisted of 2 components which were once again separated afterwards with the same eluent (Fig. 3) .
  • N 4 P 4 AzCl 7 gave a ring frequency at 1316 (broad) or 1279 cm -1 (sharp); the "aziridino" band lay at 965 cm -1 (sharp).
  • the IR spectra of the isomeric compounds N 4 P 4 Az 2 Cl 6 were clearly distinguishable. Ring frequencies varied from 1310-1334 cm -1 (broad) or from 1275-1279 cm -1 (sharp). Aziridino bands were visible from 963 to 976 cm -1 (sharp) .
  • Precipitated (polymeric) salts are removed by filtration and, after washing thoroughly with solvent, the combined filtrates containing, the P-N ring compounds are evaporated in vacuo. If acetonitrile or THF is used as solvent, the complete reaction mixture is evaporated in vacuo. Extraction with diethyl ether or benzene yields solutions of the salt-free crude products.
  • mice alive 250 (2 mice alive) (tests conducted with mice taken in groups of 5).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cephalosporin Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
EP84902089A 1983-05-06 1984-05-07 Azidirino derivatives of tetrameric cyclophosphazenes Withdrawn EP0142543A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NL8301626A NL8301626A (nl) 1983-05-06 1983-05-06 Aziridinoderivaat van een tetramere cyclochloorfosfazeenverbinding, werkwijze ter bereiding daarvan, en een door substitutie van de chlooratomen van de tetramere chloorfosfazeenverbinding afgeleid aziridinoderivaat.
NL8301626 1983-05-06

Publications (1)

Publication Number Publication Date
EP0142543A1 true EP0142543A1 (en) 1985-05-29

Family

ID=19841823

Family Applications (1)

Application Number Title Priority Date Filing Date
EP84902089A Withdrawn EP0142543A1 (en) 1983-05-06 1984-05-07 Azidirino derivatives of tetrameric cyclophosphazenes

Country Status (6)

Country Link
EP (1) EP0142543A1 (da)
JP (1) JPS60501257A (da)
AU (1) AU560606B2 (da)
DK (1) DK7485A (da)
NL (1) NL8301626A (da)
WO (1) WO1984004523A1 (da)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19947440A1 (de) * 1999-09-24 2001-04-05 Analyticon Discovery Gmbh 1-Aziridino-1-hydroxyiminomethyl-Derivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel
CN110954628B (zh) * 2019-12-19 2022-05-03 山东泰星新材料股份有限公司 一种六苯氧基环三磷腈的高效液相检测方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1493736A (fr) * 1966-07-22 1967-09-01 Soc Etu Chimiques Ind Et Agri Nouveaux dérivés du chlorure de phosphonitrile

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8404523A1 *

Also Published As

Publication number Publication date
AU2867984A (en) 1984-12-04
JPS60501257A (ja) 1985-08-08
NL8301626A (nl) 1984-12-03
AU560606B2 (en) 1987-04-09
WO1984004523A1 (en) 1984-11-22
DK7485D0 (da) 1985-01-07
DK7485A (da) 1985-01-07

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Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

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AK Designated contracting states

Designated state(s): AT BE CH DE FR GB LI LU NL SE

17P Request for examination filed

Effective date: 19850515

17Q First examination report despatched

Effective date: 19861023

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 19870303

RIN1 Information on inventor provided before grant (corrected)

Inventor name: VAN DE GRAMPEL, JOHAN, CHRISTOPH

Inventor name: VAN DER HUIZEN, ADRIAAN, ALBERT