DE2218547A1 - 4-(bis(2-chloroethyl)amino)-2,3-dimethyl-1-phenyl-5- - pyrazolone - with cancerostatic activity - Google Patents

4-(bis(2-chloroethyl)amino)-2,3-dimethyl-1-phenyl-5- - pyrazolone - with cancerostatic activity

Info

Publication number
DE2218547A1
DE2218547A1 DE19722218547 DE2218547A DE2218547A1 DE 2218547 A1 DE2218547 A1 DE 2218547A1 DE 19722218547 DE19722218547 DE 19722218547 DE 2218547 A DE2218547 A DE 2218547A DE 2218547 A1 DE2218547 A1 DE 2218547A1
Authority
DE
Germany
Prior art keywords
bis
amino
phenyl
pyrazolone
dimethyl
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
DE19722218547
Other languages
German (de)
Inventor
Walter Gutsche
Walter Jungstand
Walter Dipl Chem Dr Werner
Klaus Wohlrabe
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.)
Jenapharm GmbH and Co KG
Original Assignee
VEB Jenapharm
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 VEB Jenapharm filed Critical VEB Jenapharm
Priority to DE19722218547 priority Critical patent/DE2218547A1/en
Publication of DE2218547A1 publication Critical patent/DE2218547A1/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/18—One oxygen or sulfur atom
    • C07D231/20—One oxygen atom attached in position 3 or 5
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
    • C07D231/46—Oxygen atom in position 3 or 5 and nitrogen atom in position 4
    • C07D231/48—Oxygen atom in position 3 or 5 and nitrogen atom in position 4 with hydrocarbon radicals attached to said nitrogen atom

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Title cpd. is prepd. by chlorinating 4- bis(2-hydroxyethyl)amino -2,3-dimethyl-1-phenyl-5-pyrazolone in known manner in a suitable solvent, pref. CHCL3 or benzene, with an (in)organic acid chloride, pref. SOCl2 or POCl3, pref. at th b.pt of the solvent, and converting the resulting hydrochloride into the free base.

Description

Vorfahren zur Herstollung von 4- [Bis-(2-chloräthyl)-@mino]-2.3-dimethyl-1-phenyl-pyrazolon-(5) Die @rfindung b@trifft ein Vorfahren zur Herstellung einer neuen Bis-(2-chloräthyl)-amino-Verbindung, die als Cancerostaticum Vorwendung finden @@nn.Ancestors for the manufacture of 4- [bis- (2-chloroethyl) - @ mino] -2.3-dimethyl-1-phenyl-pyrazolone- (5) The @rfindung b @ meets an ancestor for the production of a new bis (2-chloroethyl) amino compound, which find application as Cancerostaticum @@ nn.

Die @orstellung von Bis-(2-chloräthyl)-amino-Verbindungen gelingt häufig lurch Chlorierung von Bis-(2-hydroxyäthyl)-amino-Verbindungen mit anorganischen Säurechloriden wie z. B. Phosphoroxychlorid oder Thionylchlorid.The representation of bis (2-chloroethyl) amino compounds succeeds frequently by chlorination of bis (2-hydroxyethyl) amino compounds with inorganic compounds Acid chlorides such as B. phosphorus oxychloride or thionyl chloride.

@in Verfahren zur Herstollung von 4-[Bis-(2-hydroxyäthyl)-amino]-2.3-dimethyl-1-phenyl-pyrazolon-(5) ist bekannt.In a process for the production of 4- [bis- (2-hydroxyethyl) -amino] -2.3-dimethyl-1-phenyl-pyrazolone- (5) is known.

@ine Überfährung dieser Bis-(2-hydroxyäthyl)-Verbindung in die Bis-(2-chloräthyl)-Verbindung ist bisher nicht beschrieben worden.A conversion of this bis (2-hydroxyethyl) compound into the bis (2-chloroethyl) compound has not yet been described.

@s ist bekannt, daß bestimmte Bis-(2-chloräthyl)-amino-V@rbindungen experimentelle und menschliche Tumoren günstig beeinflussen können. Zweck der Erfindung ist die Herstellung von 4-[Bis-(chloräthyl)-amino]-2.3-dimethyl-1-phenyl-pyrazolon-(5) zur Therapie von Tumorerkrankungen.It is known that certain bis- (2-chloroethyl) -amino-V @ rbindungen can favorably influence experimental and human tumors. Purpose of the invention is the production of 4- [bis- (chloroethyl) -amino] -2.3-dimethyl-1-phenyl-pyrazolon- (5) for the therapy of tumor diseases.

Der @@findung liegt die Auf@@be zugrunde, 4-[Bis-(2-hydroxyäthyl)-amino]-2.3-dimethyl-1-phenyl-pyrazolon-(5) in die entsprechende Bis-(2-chloräthyl-Verbindung zu überführen.The @@ finding is based on the Auf @@ be, 4- [bis- (2-hydroxyethyl) -amino] -2.3-dimethyl-1-phenyl-pyrazolone- (5) to convert into the corresponding bis (2-chloroethyl compound.

@rfindungsgemäß wird diese Aufgabe dadurch gelöst, daß man 4-[Bis-(2-hydroxyäthyl)amino]-2.3-dimethyl-1-phenyl-pyrazolon -(5) in an sich bokannter Weise in einem Lösungsmittel Vie Chloroform oder Benz ei löst und mit Thionylchlorid oder Phosphoroxychlorid oder anderen geeigneten anorganischen oder oganischen Säurechloriden chloriert.According to the invention, this object is achieved by using 4- [bis- (2-hydroxyethyl) amino] -2.3-dimethyl-1-phenyl-pyrazolone - (5) dissolves in a known manner in a solvent such as chloroform or benzene and with thionyl chloride or phosphorus oxychloride or other suitable inorganic ones or organic acid chlorides.

Vorteilhaft wird die Mischung zum Sieden erhitzt. Die Säurechloride können auch zu der siedenden Lösung der Hydroxy-Verbindung in Chloroform gegeben werden. Aus dem gewonnenen Hydrochlorid kann die freie Base in kristalliner Form erhalten werden.The mixture is advantageously heated to the boil. The acid chlorides can also be added to the boiling solution of the hydroxy compound in chloroform will. The free base can be obtained in crystalline form from the hydrochloride obtained can be obtained.

Es wurde überraschend gefunden, daß 4- Bis-(2-chloräthyl)-amino]-2.3-dimethyl-1-phenyl-pyrazolon-(5) (IMET 3995) eine ausgeprägte und breite cancerostatische Wirkung mit günstigen therapeutischen Indices besitzt. Die experimentelle Prüfung (5) an Transplantationstumoren der Maus erbrachte u. a. bei i. p. Applikation foic;ende nisse: (Zur Methode siehe W. Jungstand, W. Gutsche, K. Wohlrabe, Dreistufentest als Screening-Programm für potentielle Cancerostatika, in Vorbereitung).It has surprisingly been found that 4- bis (2-chloroethyl) amino] -2.3-dimethyl-1-phenyl-pyrazolone- (5) (IMET 3995) a pronounced and broad cancerostatic effect with favorable therapeutic Owns indices. The experimental test (5) on mouse transplant tumors provided inter alia at i. p. Application foic; ende nisse: (For the method, see W. Jungstand, W. Gutsche, K. Wohlrabe, three-stage test as a screening program for potential cancerostatic agents, in preparation).

Leukämie LAJ I: 98% maximale Verlängerung der Überauf ABAF#u. # lebenszeit (Dosis : 25 mg/kg Maus) Sarkom 180/P: 38,7% maximale Tumorgewichtsminderung auf AB/kol # (Dosis : 6.25 mg/kg Maus) pas entspricht den Hemmeffekten, die mit Sarkolysin R (p-[bis-(2-chloräthyl)-amino]-DL-phenylalanin) bei den gleichen Tumoren unter gleichen Bedingungen zu erreichen sind. IMET 3995 ist jedoch weniger toxisch als Sarkolysir wie es die Toxizitätsbestimmung an ABÄF1-Mäusen zeigt.Leukemia LAJ I: 98% maximum prolongation of excess to ABAF # u. # lifetime (Dose: 25 mg / kg mouse) Sarcoma 180 / P: 38.7% maximum tumor weight reduction AB / kol # (dose: 6.25 mg / kg mouse) pas corresponds to the inhibiting effects with sarcolysin R (p- [bis- (2-chloroethyl) -amino] -DL-phenylalanine) in the same tumors under equal conditions can be achieved. However, IMET 3995 is less toxic than Sarcolyser as shown by the toxicity determination on ABÄF1 mice.

IMET 3995 Sarkolysin R LD50 akut 87,5 mg/kg 25,5 mg/kg 1 x i.p. IMET 3995 Sarcolysin R LD50 acute 87.5 mg / kg 25.5 mg / kg 1 x i.p.

LD50 subakut 18,2 mg/kg 3,5 mg/kg 9 x i.p. LD50 subacute 18.2 mg / kg 3.5 mg / kg 9 x i.p.

Sarkolysin # besitzt also eine stärkere Neigung zur Kumulation. Sarcolysin # has a stronger tendency to accumulate.

Für IMET 3995 ergeben sich folgende Indices, die im Vergleich zu denen des Sarkolysins # in der folgenden mabelle aufgeführt sind. The following indices result for IMET 3995, which are compared to those of sarcolysin # are listed in the following table.

Therap. Indices mit Vertrauensintervallen bei 95%iger Erfüllungswahrscheinlichkeit TI IMET 3995 Sarkolysin # LAJ I LD50 akut = 8.6-14.0-22.8 8.9.-14.6-23.8 VU50 Sa 180/P LD50 akut = 5.2-10.9-23.2 5.5-9.6-16.9 TGM50 LAJ I LD50 subakut = 1.8.-2.9-4.5 1.5-2.1-2.7 VU50 Sa 180/P LD50 subakut = 1.1-2.3-4.7 0.9-1.4-2.0 TGM50 Erläuterungen der Abkürzungen : LD50: Letale Dosis für 50% der Tiere VU50: Dosis, bei der eine 50%ige Verlängerung der Überlebenszeit der behandelten Tiere gegenüber den Kontrollen eintritt. Therap. Indices with confidence intervals with a 95% probability of fulfillment TI IMET 3995 Sarcolysin # LAJ I LD50 acute = 8.6-14.0-22.8 8.9.-14.6-23.8 VU50 Sa 180 / P LD50 acute = 5.2-10.9-23.2 5.5-9.6-16.9 TGM50 LAJ I LD50 subacute = 1.8.-2.9-4.5 1.5-2.1-2.7 VU50 Sa 180 / P LD50 subacute = 1.1-2.3-4.7 0.9-1.4-2.0 TGM50 Explanations of abbreviations: LD50: Lethal dose for 50% of the animals VU50: Dose at which one 50% prolongation of the survival time of the treated animals compared to the controls entry.

TGM: Dosis, bei der eine 50%ige Gewichtsminderung der behandelten soliden Tumoren gegenüber den Kontrollen eintritt. TGM: dose at which a 50% weight reduction of the treated solid tumors occurs versus controls.

IMET 3995 ist an der transplantablen Leukämie LAJ I ferner auch nach subkutoner, intramuskuläer und oraler Applikation gut wirksam. Einen guten canceroststischen Effekt zeigt die Substanz ferner bei den soliden Tumoren Sarkom 180/G, Ilasmozytom 5 I und WA 256.IMET 3995 is also after the transplantable leukemia LAJ I effective subcutaneous, intramuscular and oral administration. A good cancerostatic table The substance also has an effect on the solid tumors of sarcoma 180 / G and ilasmocytoma 5 I and WA 256.

Das erfindungsgemäße chemische Vorfahren soll an folgenden Bei spielen erläutert werden: Beispiel 1: 2.91 g (0,01 Mol) 4-[Bis-(2-hydroxyäthyl)-amino]-2.3-dimethyl-1-phenyl-pyrazolon-(5) werden in 20 ml trockenem Chloroform gelöst, Chlorwassarstoff bis zur Sättigung eingeleitet, und die Lösung zum Sieden erhitzt. Unter Rühren und Feuchtigkeitsausschluß werden während 60 Minuten 3.57 g (0,03 Ml0 Thionylchlorid in 10 ml Chloroform zugotropft.The chemical process according to the invention is intended to play on the following examples are explained: Example 1: 2.91 g (0.01 mol) 4- [bis- (2-hydroxyethyl) -amino] -2.3-dimethyl-1-phenyl-pyrazolone- (5) are dissolved in 20 ml of dry chloroform, hydrogen chloride to saturation initiated, and the solution heated to boiling. With stirring and exclusion of moisture 3.57 g (0.03 ml of thionyl chloride in 10 ml of chloroform are added dropwise over the course of 60 minutes.

Die Reaktionsmischung färbt sich dunkol. Nach d chloridzugabe wird weitere 15 Minuten unter Rückfluß ,ekocht. Überschüssiges Thionylchlorid wird durch vorsichtige Zugabe von 5 ml Äthanol und anschließendes Aufkochen beseitigt. Man destilliert das Lösungsmittel ab, zuletzt im Vakuum. Der Rückstand wird mit Wasser und Äther suspendiert, mit Sodalösung alkalisch gemacht und die Base in 50 ml Äther aufgenommen. Die wäßrige Phase extraiiert man noch einmal mit 30 ml Äther. Die vereinigten Ätherlösungen werden mit Natriumsulfat getrocknet, filtriert und mit Chlorwasserstoff die Base eis Hydrochlorid ölig abgeschieden. Durch geeigneten Zusatz von äthanol und Essigester und Stehenlassen im Kihlschrank kristallisieren 1 bis 5 g 4-(2-chloräthyl)amino]-2.3-dimethyl-1-phenyl-pyrazolon-(5)-hydrochlorid. Durch Umkristallisation aus Äthanol/Essigester/Äther erhält man farblose kristalle vom F. 107 bis 1100.The reaction mixture turns dark. After the addition of chloride reflux for another 15 minutes, boil. Excess thionyl chloride will through careful addition of 5 ml of ethanol and subsequent boiling eliminated. Man the solvent is distilled off, finally in vacuo. The residue is washed with water and ether suspended, made alkaline with soda solution and the base in 50 ml of ether recorded. The aqueous phase is extracted again with 30 ml of ether. The United Ether solutions are with Sodium sulfate dried, filtered and with hydrogen chloride, the base was deposited in an oily form with ice hydrochloride. By suitable Adding ethanol and ethyl acetate and leaving to stand in the refrigerator crystallize 1 to 5 g of 4- (2-chloroethyl) amino] -2.3-dimethyl-1-phenyl-pyrazolone- (5) hydrochloride. Colorless crystals are obtained by recrystallization from ethanol / ethyl acetate / ether from F. 107 to 1100.

Beispiel 2: 2.91 g (0,01 Mol) 4-[Bis-(2-hydroxyäthyl)amino]-2.3-dimothyl-1-phenyl-pyrazolon-(5) werden in 20 ml trockenem Chloroform gelöst und unter Feu-chtigkeitsausschluß bei 200 3.1 g (0,02 Mol0 Phosphoroxychlorid in 10 ml Chloroform während 30 Minuten unter Rühren zugetropft. Man läßt 60 Minuten unter Rückfluß sieden, dampft die helle Reaktionsmischung, im Vakuum ein und arbeitet den Riickstand, wie im Beispiel 1 beschrieben wurde, auf. Man erhält etwa 1,8 g 4-[Bis-(2-chloräthyl)amino]-2.3-dimethyl-1-phenyl-pyrazolon-(5)-hydrochlorid als Rohprodukt.Example 2: 2.91 g (0.01 mol) 4- [bis- (2-hydroxyethyl) amino] -2.3-dimothyl-1-phenyl-pyrazolone- (5) are dissolved in 20 ml of dry chloroform and removed from moisture 200 3.1 g (0.02 mol of phosphorus oxychloride in 10 ml of chloroform for 30 minutes under Stir added dropwise. The mixture is refluxed for 60 minutes, the pale reaction mixture is evaporated, in a vacuum and works the residue as described in Example 1, on. About 1.8 g of 4- [bis- (2-chloroethyl) amino] -2.3-dimethyl-1-phenyl-pyrazolone- (5) hydrochloride are obtained as a raw product.

3,6 g reines Hydrochlorid werden in 5 ml Wasser verrieben bis sich die Base 4-[Bis-(2-chloräthyl)-amino]-2.3-dimethyl-1-phenyl-pyrazolon-(5) kristallin abscheidet. Man orhält 2,5 g farblose kristalle vom F. 70°.3.6 g of pure hydrochloride are triturated in 5 ml of water until dissolved the base 4- [bis- (2-chloroethyl) -amino] -2.3-dimethyl-1-phenyl-pyrazolone- (5) is crystalline separates. 2.5 g of colorless crystals with a melting point of 70 ° are obtained.

Claims (3)

P a t e n t a n s p r ü c h eP a t e n t a n s p r ü c h e Verfahren zur Herstellung von 4-[Bis-(2-chloräthyl)-amino]-2.3-dimethyl-1-phenyl-pyrazolon-(5), d a d u r c h g e k e n n z e i c h n e t, daß 4-[Bis-(2-hydroxyäthyl)-amino]-2.3-dimethyl-1-phenyl-pyrazolon-(5) in an sich bekannter Weise in einem geeigneten Lösungsmittel, vorzugsweise ChloroSorm oder Benzol, mit einem anorganischen oder organischen Säurechlorid, vorzugsweise mit Thionylchlorid oder Phosphoroxychlorid chloriert und das erhaltene Hydrochlorid in die freie Base überführt wird. Process for the preparation of 4- [bis- (2-chloroethyl) -amino] -2.3-dimethyl-1-phenyl-pyrazolone- (5), d a d u r c h g e k e n n n z e i c h n e t that 4- [bis- (2-hydroxyethyl) -amino] -2.3-dimethyl-1-phenyl-pyrazolone- (5) in a manner known per se in a suitable solvent, preferably ChloroSorm or benzene, with an inorganic or organic acid chloride, preferably chlorinated with thionyl chloride or phosphorus oxychloride and the hydrochloride obtained is converted into the free base. 2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß man die Chlorierung bei der Siedetemperatur des Lösungsmittels durchführt.2. The method according to claim 1, characterized in that the Carries out chlorination at the boiling point of the solvent. 3. 4-[Bis-(2-chloräthyl-amino]-2.3-dimethyl-1-phenyl pyrazolon-(5).3. 4- [bis- (2-chloroethyl-amino] -2.3-dimethyl-1-phenyl pyrazolone- (5).
DE19722218547 1972-04-17 1972-04-17 4-(bis(2-chloroethyl)amino)-2,3-dimethyl-1-phenyl-5- - pyrazolone - with cancerostatic activity Pending DE2218547A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE19722218547 DE2218547A1 (en) 1972-04-17 1972-04-17 4-(bis(2-chloroethyl)amino)-2,3-dimethyl-1-phenyl-5- - pyrazolone - with cancerostatic activity

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19722218547 DE2218547A1 (en) 1972-04-17 1972-04-17 4-(bis(2-chloroethyl)amino)-2,3-dimethyl-1-phenyl-5- - pyrazolone - with cancerostatic activity

Publications (1)

Publication Number Publication Date
DE2218547A1 true DE2218547A1 (en) 1973-10-31

Family

ID=5842226

Family Applications (1)

Application Number Title Priority Date Filing Date
DE19722218547 Pending DE2218547A1 (en) 1972-04-17 1972-04-17 4-(bis(2-chloroethyl)amino)-2,3-dimethyl-1-phenyl-5- - pyrazolone - with cancerostatic activity

Country Status (1)

Country Link
DE (1) DE2218547A1 (en)

Similar Documents

Publication Publication Date Title
DE1493920C3 (en) Amino ethers and their pharmacologically non-toxic salts and quaternary ammonium compounds with methyl iodide and processes for their preparation
DE2265138C3 (en) Vincamic acid benzyl ester, its salts with acids, a process for their preparation and pharmaceutical agents
DE2725246C2 (en)
DE2218547A1 (en) 4-(bis(2-chloroethyl)amino)-2,3-dimethyl-1-phenyl-5- - pyrazolone - with cancerostatic activity
DE2238304C3 (en) (Choleretically active) esters or salts of dehydrocholic acid, processes for their production and medicinal preparations containing these compounds
DE1493618A1 (en) Coumarin derivatives and a process for their preparation
DE2403786A1 (en) NEW DERIVATIVES OF CUMARINE
DE870561C (en) Process for the preparation of ethers of p-nitrophenol
DE442655C (en) Process for the preparation of cyclohexenylalkylbarbituric acids
DE969245C (en) Process for the production of new spasmolytically effective basic esters of ª ‡ -alkylated phenylacetic acids
DE1445969C (en) Process for the preparation of basic 3,4,5 trimethoxybenzoic acid esters
DE2406849C3 (en) Nicotinic acid trans-3,3,5-trimethylcyclohex-1-yl ester, process for its preparation and medicament containing this ester
AT234700B (en) Process for the preparation of the new 2-methyl-3- (2'-methyl-3'-chlorophenyl) -quinazolons- (4)
DE2236005C3 (en) Dibenzagonal bracket on d, square bracket for -dioxepin- square bracket for 1.3 square bracket for -derivatives and their pharmacologically acceptable salts, as well as processes for their production and pharmaceuticals containing them
DE1418540C (en) Process for the preparation of 1,3,2 dioxaborolanes or 1,3,2 dioxabonnanes
DE2145686C3 (en) 2-chloro-S-sulfamylbenzoic acid derivatives, processes for their preparation and pharmaceuticals containing these compounds
DE1814334B2 (en) FATTY ACID AMIDES AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS
CH527159A (en) Quaternary nitrogen derivs of salicylic acid
AT214928B (en) Process for the preparation of new camphidinium compounds
DE2221281A1 (en) Pyrazole derivatives and processes for their preparation
DE2238260C3 (en) Phosphoric acid monoester of 5- (2-dimethylaminoethoxy) -carvacrol, process for its preparation and pharmaceuticals containing it
AT226241B (en) Process for the preparation of the new cyclohexylisopropylmethylamine salt of phenylethylbarbituric acid
AT203512B (en) Process for the production of new neutral bis-phosphoric acid esters
DE839938C (en) Process for the preparation of new dialkylamides from alkoxy-substituted benzoic acids
DE1900948C (en) Cis- and trans-2-methyl-5- (3, 4, S-trimethoxybenzamidoJ-decahydroisoquinoline