DE1920198A1 - Daunomycin derivatives with anti-cancer activity - Google Patents

Daunomycin derivatives with anti-cancer activity

Info

Publication number
DE1920198A1
DE1920198A1 DE19691920198 DE1920198A DE1920198A1 DE 1920198 A1 DE1920198 A1 DE 1920198A1 DE 19691920198 DE19691920198 DE 19691920198 DE 1920198 A DE1920198 A DE 1920198A DE 1920198 A1 DE1920198 A1 DE 1920198A1
Authority
DE
Germany
Prior art keywords
daunomycin
derivatives
cancer activity
formula
nhr
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.)
Pending
Application number
DE19691920198
Other languages
German (de)
Inventor
Graziana Canevazzi
Marcello Gaetani
Arpad Grein
Aurelio Di Marco
Piergiuseppe Orezzi
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.)
Pfizer Italia SRL
Original Assignee
Farmaceutici Italia SpA
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 Farmaceutici Italia SpA filed Critical Farmaceutici Italia SpA
Publication of DE1920198A1 publication Critical patent/DE1920198A1/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/20—Carbocyclic rings
    • C07H15/24—Condensed ring systems having three or more rings
    • C07H15/252—Naphthacene radicals, e.g. daunomycins, adriamycins

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)

Description

MTMTMfWM.*MTMTMfWM. *

WtO^AWISWtO ^ AWIS

Mb*». W, IQMtMb * ». W, IQMt

foe. F«re»c*uttci.foe. F «re» c * uttci.

Daunomycinderivate mit krebshemeender AktivitätDaunomycin derivatives with anti-cancer activity

Die vorliegende Erfindung bezieht sich tuf D«uno*yoinderivate sit krebth««*nd«r Aktivitlt und auf «in Verfahren su daran Harctallung.The present invention relates to D «uno * yoin derivatives sit krebth "" * nd "r activity and on" in proceedings see Harctallung.

Xn StajBMpatent Kr. 1 21S 9%H ά*ν AnmaXdarin wardan daa Antibiotikum Daunoeycin, do« Varfahren su seiner KeretelXung aus Straptosyoas peucatius, »eine Salz« mit nicht toxieohen organischen und anorganischan Stur#n und das Produkt seines hydrolytischen Abbaus, das Aglykon Daunomyoinon, beschrieben und beansprucht*Xn StajBMpatent Kr. 1 21S 9% H ά * ν AnmaXdarin daa antibiotic Daunoeycin, do "Varfahren su his KeretelXung from Straptosyoas peucatius," a salt "with non-toxic organic and inorganic stur # n and the product of its hydrolytic breakdown, the aglycon Daunomyoinon, described and claimed *

Es wurde nun gefunden, daß stan durch Behandlung von Daunomycin mit Samicarbasids Thioeemicarbazid oder deren Alky!derivate die Derivat· der folgenden Formel erhilt:It has now been found that stan by treating daunomycin with Samicarbasid s Thioeemicarbazid or their derivatives alky the derivative · the following formula erhilt!:

BAD ORIGINALBATH ORIGINAL

NH-C- NHR«NH-C- NHR "

worin R Sauerstoff oder Schwefel und R1 Wasserstoff, Methyl oder Äthyl bedeutet. Di·»· Verbindungen aind in der Therapie als krebshemmende Mittel nut»lieh.where R is oxygen or sulfur and R 1 is hydrogen, methyl or ethyl. The compounds are used in therapy as anti-cancer agents.

Insbesondere wird nach dem Verfahren der vorliegenden Erfindung Daunomycin mit einem Seaicarbasid oder Thiosemicarbasid der FormelIn particular, according to the method of the present invention, daunomycin is treated with a seaicarbasid or thiosemicarbasid the formula

H9H - NH - C ~ NHi1 , HH 9 H - NH - C ~ NHi 1 , H

worin. K and R* die obige Bedeutung haben, bei einem pH-Wert !wischen 7 und S,S umgesetzt. Das ReaJctionsgemlsch wird mit einem geeigneten Lösungsmittel, wie Chloroform, Butanol oder Methylenohlorid extrahiert und schließlich wird dae entsprechende Semicarbason oder Thioeemicarbason in an sich bekannter Weise abgetrennt *wherein. K and R * have the above meaning at a pH ! wipe 7 and S, S implemented. The reaction mixture is with a suitable solvent such as chloroform, butanol or Methylene chloride is extracted and finally the corresponding Semicarbason or thioeemicarbason in a manner known per se separated *

909848/13*1909848/13 * 1

BAD C~;C1MALBATH C ~; C1MAL

Di« folgenden Beispiele «ollen die vorliegende Erfindung näher erläutern, ohne ei« jedoch hierauf zu beschränken.The following examples are intended to explain the present invention in greater detail without, however, restricting it thereto.

BEISPIEL 1: paunoffiycin-semicarba&onEXAMPLE 1: paunoffiycin-semicarba & on

0,3 g Daunoaycinhydrochlorid werden in 15 ml Wasser gelöst und mit 0,6 g Secticarbazidhydrochlorid versetzt. Die Lö3ung wird mit O»1N Natriumhydroxyd auf einen pH-Wert von 7,5 eingestellt und «ine Nacht lang bei Raumtemperatur stehen tblassen Die Reaktionsmischung wird mehrmals mit Chloroform extrahiert und der Extrakt ergibt durch Eindampfen zur Trocken« unter verminderte» Druck ein«n Rückstand, der axt Äthanol auf·* genome»·η und mit Äther autgefällt wird. Man erhält 0,1 g Daunomycin-eeaicarbason, das bei 264°C schmilzt.0.3 g of daunoaycin hydrochloride are dissolved in 15 ml of water dissolved and treated with 0.6 g of secticarbazide hydrochloride. the The solution is brought to a pH of 7.5 and stand overnight at room temperature The reaction mixture is washed several times with chloroform extracted and the extract gives by evaporation to dryness "under reduced" pressure a "n residue, the ax ethanol on · * genome »· η and is precipitated with ether. 0.1 g of daunomycin eeaicarbason is obtained, which melts at 264 ° C.

BEISPIEL ti Daunottycin-thioteaicarbazon EXAMPLE ti Daunottycin-thioteaic arbazon

0,3 g Daunonycinbas« und 0,6 g Thiosemicarbazidhydro-' Chlorid werden in 20 »1 Wasser gelöst. Die Lösung wird mit 0,111 Natriumhydroxyd auf «inen pH-Wert von 7,5 gebracht, «in« Nacht lang bei Raumtemperatur stehen g«laseen und auf tine» Wasserbad ein« Stund« lang «rwtrmt. Das Reaktionegemisch wird s*hrmals mit Chloroform extrahiert. Der Extrakt ergibt nach Eindampfen zur Trocken* unter vermindertem Druck 0,2 g Daunomycin*· thioeemlcarbazon, das bei 226 - 228°C schmilzt.0.3 g daunonycinbas and 0.6 g thiosemicarbazide hydro- ' Chloride are dissolved in 20 »1 water. The solution is 0.111 Sodium hydroxide brought to a pH of 7.5 "in" night Stand at room temperature for a long time, glass and put on a tine water bath warmed up for an “hour”. The reaction mixture becomes twice extracted with chloroform. The extract gives after evaporation to dryness * under reduced pressure 0.2 g daunomycin * thioeemlcarbazon, which melts at 226-228 ° C.

909848/1391909848/1391

BAD ORIGINALBATH ORIGINAL

Claims (3)

Patentansprüche :Patent claims: Verfahren zur Herstellung von Daunomycinderivaten der allgemeinen FormelProcess for the preparation of daunomycin derivatives of general formula CH3 CH 3 C ■ N - NH - C - NHR1 C ■ N - NH - C - NHR 1 Il RIl R worin R Sauerstoff od«r Schwefel und R1 Wasserstoff, Methyl oder Äthyl bedeutet, dadurch gekennzeichnet, daß das Antibiotikum Daunomycin mit einer Verbindung der Formelin which R is oxygen or sulfur and R 1 is hydrogen, methyl or ethyl, characterized in that the antibiotic daunomycin with a compound of the formula H.H -KH-C- NHR» 2 IHH -KH-C- NHR » 2 I. , (II), (II) worin R und R1 die obige Bedeutung haben, bei einem pH-Wert zwischen 7 und 8,5 uageeetst und das entsprechende Daunomycinderivat abgetrennt wird.wherein R and R 1 have the above meaning, uageeetst at a pH value between 7 and 8.5 and the corresponding daunomycin derivative is separated off. 2.2. 9098^8/13819098 ^ 8/1381 BAD -O1 BAD -O 1 19201111920111 -s--s- 2. Ein Derivat des Antibiotikunis Daunomycin der in Anspruch 1 angegebenen Formel Z, worin R und R1 die angegeben« Bedeutung haben.2. A derivative of the antibiotic daunomycin of the formula Z given in claim 1, wherein R and R 1 have the meaning given. 3. Daunömycin-semicarbazon.3. Daunomycin semicarbazone. if. Daunomycin-thiosemicarbazon.if. Daunomycin thiosemicarbazone. 909848/1381909848/1381 BAD ORIGINALBATH ORIGINAL
DE19691920198 1968-04-24 1969-04-21 Daunomycin derivatives with anti-cancer activity Pending DE1920198A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
IT1563968 1968-04-24

Publications (1)

Publication Number Publication Date
DE1920198A1 true DE1920198A1 (en) 1969-11-27

Family

ID=11148142

Family Applications (1)

Application Number Title Priority Date Filing Date
DE19691920198 Pending DE1920198A1 (en) 1968-04-24 1969-04-21 Daunomycin derivatives with anti-cancer activity

Country Status (3)

Country Link
DE (1) DE1920198A1 (en)
FR (1) FR2007500A6 (en)
GB (1) GB1217135A (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102603824A (en) * 2011-12-15 2012-07-25 河南师范大学 New 3'-azido daunorubicin-13-thiosemicarbazone compound with cancer resistance and preparation method thereof

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1578722A (en) * 1967-10-18 1969-08-22

Also Published As

Publication number Publication date
GB1217135A (en) 1970-12-31
FR2007500A6 (en) 1970-01-09

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