CH658246A5 - METHOD FOR PRODUCING SUBSTITUTED 2,4-DIAMINO-5-BENZYLPYRIMIDINES. - Google Patents

METHOD FOR PRODUCING SUBSTITUTED 2,4-DIAMINO-5-BENZYLPYRIMIDINES. Download PDF

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Publication number
CH658246A5
CH658246A5 CH6481/82A CH648182A CH658246A5 CH 658246 A5 CH658246 A5 CH 658246A5 CH 6481/82 A CH6481/82 A CH 6481/82A CH 648182 A CH648182 A CH 648182A CH 658246 A5 CH658246 A5 CH 658246A5
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Switzerland
Prior art keywords
diamino
acid
alkyl
compound
hydrogen
Prior art date
Application number
CH6481/82A
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German (de)
Inventor
Roy Archibald Jun Swaringen
John Fred Eaddy Iii
Thomas Ranney Henderson
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Wellcome Found
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Publication of CH658246A5 publication Critical patent/CH658246A5/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/30—Halogen atoms or nitro radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10—Antioedematous agents; Diuretics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • C07D239/49—Two nitrogen atoms with an aralkyl radical, or substituted aralkyl radical, attached in position 5, e.g. trimethoprim
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings

Description

Die vorliegende Erfindung betrifft ein Verfahren zur Herstel-25 lung einer Gruppe von substituierten 2,4-Diamino-5-benzylpyri-midinen. The present invention relates to a process for the production of a group of substituted 2,4-diamino-5-benzylpyriminines.

Die deutsche Patentanmeldung Nr. 2 443 682 offenbart unter anderem Verbindungen der Formel I German patent application No. 2 443 682 discloses, inter alia, compounds of the formula I.

30 30th

35 35

wonn bliss

R4 gleich Wasserstoff oder Cw-Alkyl, R4 is hydrogen or Cw-alkyl,

R4a gleich Q-4-Alkyl und R4a is Q-4 alkyl and

R5 und R6 gleich oder verschieden sind und je Halogen, Cw-Alkyl oder C^-Alkoxy bedeuten, R5 and R6 are the same or different and each represent halogen, Cw-alkyl or C ^ -alkoxy,

dadurch gekennzeichnet, dass man eine Verbindung der Formel IV characterized in that a compound of formula IV

(IV) (IV)

CH CH

(I) (I)

mit 2,4-Diamino-5-hydroxymethyl-pyrimidin oder einem entsprechenden Ci_4-Äther umsetzt und die erhaltene Verbindung der Formel III, wo R4a Wasserstoff bedeutet, N-alkyliert wird. with 2,4-diamino-5-hydroxymethyl-pyrimidine or a corresponding Ci_4 ether and the resulting compound of formula III, where R4a is hydrogen, is N-alkylated.

3. Verfahren nach Anspruch 1 zur Herstellung einer Verbindung 3. The method according to claim 1 for the preparation of a compound

R4R4äN R4R4äN

worin wherein

R4 Wasserstoff oder Cw-Alkyl, R4 is hydrogen or Cw-alkyl,

R4a Wasserstoff und R4a is hydrogen and

R5 und R6 gleich oder verschieden sind und je Halogen, Cj_t-Alkyl oder CM-Alkoxy bedeuten, R5 and R6 are the same or different and each represent halogen, Cj_t-alkyl or CM-alkoxy,

dadurch gekennzeichnet, dass man eine Verbindung der Formel IV characterized in that a compound of formula IV

40 und deren Salze, worin 40 and their salts, wherein

R1 und R2 gleich oder verschieden sind und je C^-AIkyl, Ci_3-Alkoxy, C2__3-Alkenyl oder C2-3-Alkenyloxy und R1 and R2 are the same or different and each is C ^ alkyl, Ci_3 alkoxy, C2__3 alkenyl or C2-3 alkenyloxy and

Z Amino oder alkylsubstituiertes Amino bedeuten. Z is amino or alkyl-substituted amino.

Diesen Verbindungen wird antibakterielle Aktivität zuge-45 schrieben und für 2,4-Diamino-5-(4-amino-3,5-dimethoxyben-zyl)pyrimidin wurde nachträglich gefunden, dass es gute diureti-sche Aktivität besitzt. Antibacterial activity is attributed to these compounds and it was subsequently found that 2,4-diamino-5- (4-amino-3,5-dimethoxybenzyl) pyrimidine had good diuretic activity.

Die deutsche Patentanmeldung Nr. 2 634 358 offenbart unter anderem Verbindungen der Formel II The German patent application No. 2 634 358 discloses inter alia compounds of the formula II

50 50

55 55

60 und deren Salze, worin 60 and their salts, wherein

R3 ein Halogen und R3 is a halogen and

Z Amino oder alkylsubstituiertes Amino bedeutet. Z means amino or alkyl-substituted amino.

Diesen Verbindungen wurde ebenfalls antibakterielle Aktivität zugeschrieben. Antibacterial activity has also been attributed to these compounds.

65 Eine neue Synthese der Verbindungen der Formeln I und II wurde nun gefunden. 65 A new synthesis of the compounds of the formulas I and II has now been found.

Entsprechend betrifft die vorliegende Erfindung ein Verfahren zur Herstellung einer Verbindung der Formel III Accordingly, the present invention relates to a process for the preparation of a compound of formula III

3 3rd

658 246 658 246

Dieses Verfahren ist besonders geeignet zur Herstellung jener Verbindungen, worin R4 Wasserstoff bedeutet. This method is particularly suitable for the preparation of those compounds in which R4 is hydrogen.

Geeignete Reste R5 und R6 sind gleich und bedeuten je Methoxy, Chlor oder CM-Alkyl. Suitable radicals R5 and R6 are the same and each represent methoxy, chlorine or CM-alkyl.

Das Verfahren wird zweckmässig in einem Lösungsmittel durchgeführt, das beide Reaktanden zu lösen vermag ; besonders geeignet sind polare, nicht phenolische Lösungsmittel, bei einer nicht extremen Temperatur, z. B. zwischen 25 und 175 °C, und besonders bevorzugt zwischen 50 und 150 °C. Die Reaktion wird bevorzugt in Anwesenheit einer Säure, z. B. Chlorwasserstoff oder Salzsäure (hydrochloric acid) oder Essig-, Methansulfon-oder p-Toluolsulfonsäure, durchgeführt. Ein besonders bevorzugtes Lösungsmittel ist Essigsäure. The process is expediently carried out in a solvent which is capable of dissolving both reactants; polar, non-phenolic solvents are particularly suitable, at a non-extreme temperature, e.g. B. between 25 and 175 ° C, and particularly preferably between 50 and 150 ° C. The reaction is preferably carried out in the presence of an acid, e.g. Example, hydrochloric acid or hydrochloric acid or acetic, methanesulfonic or p-toluenesulfonic acid. A particularly preferred solvent is acetic acid.

Beispiel example

Herstellung von2,4-Diamino-5-(4-amino-3,5-dimethoxy- Preparation of 2,4-diamino-5- (4-amino-3,5-dimethoxy-

benzyl)pyrimidin Eine Mischung von 2,4-Diamino-5-hydroxymethylpyrimidin (4,30 g, 30,0 mMol), hergestellt aus 2,4-Diamino-5-cyanopyrimi-din (wie beschrieben im britischen Patent Nr. 1413 472) ,2,6-Dimethoxyanilin (5,05 g, 33,0 mMol) Essigsäure (60 ml) und konzentrierter Salzsäure (4,2 ml) wurde während 4/i h unter Rückfluss erhitzt, gekühlt und filtriert, wobei das Hydrochlorid-salz der Titelverbindung entstand (7,13 g, 76,2%). Das Salz wurde in Wasser gelöst, und die Lösung wurde mit konzentriertem Ammoniumhydroxid basisch gestellt. Der resultierende Niederschlag wurde filtriert, mit Wasser gewaschen und getrocknet, wobei die Titelverbindung erhalten wurde (5,18 g, 67,2%). Q3HJ7N5O2: benzyl) pyrimidine A mixture of 2,4-diamino-5-hydroxymethylpyrimidine (4.30 g, 30.0 mmol) made from 2,4-diamino-5-cyanopyrimidine (as described in British Patent No. 1413,472 ), 2,6-Dimethoxyaniline (5.05 g, 33.0 mmol) acetic acid (60 ml) and concentrated hydrochloric acid (4.2 ml) was refluxed during 4 / ih, cooled and filtered, the hydrochloride salt the title compound was obtained (7.13 g, 76.2%). The salt was dissolved in water and the solution was basified with concentrated ammonium hydroxide. The resulting precipitate was filtered, washed with water and dried to give the title compound (5.18 g, 67.2%). Q3HJ7N5O2:

berechnet: C 56,72; H 6,22; N 25,44 gefunden: C 56,63; H 6,29; N 25,39. calculated: C 56.72; H 6.22; N 25.44 Found: C 56.63; H 6.29; N 25.39.

Andere Verbindungen der Formel III, hergestellt nach diesem Verfahren sind in Tabelle I erläutert. Other compounds of formula III prepared by this process are illustrated in Table I.

Tabelle I Table I

R4 R4

R5 R5

R6 R6

berechnet Ausbeute,% C calculates yield,% C

H H

N N

gefunden C found C

H H

N N

H H

CHMe2 CHMe2

CHMe2 CHMe2

55,1 55.1

68,19 68.19

8,42 8.42

23,39 23.39

68,08 68.08

8,49 8.49

23,17 23.17

H H

Et Et

Et Et

61,4 61.4

66,39 66.39

7,80 7.80

25,81 25.81

66,14 66.14

8,03 8.03

25,71 25.71

H H

Me Me

Me Me

70,7 70.7

64,17 64.17

7,05 7.05

28,78 28.78

63,94 63.94

6,97 6.97

28,79 28.79

H H

Me Me

Et Et

63,3 63.3

65,34 65.34

7,44 7.44

27,21 27.21

65,03 65.03

7,49 7.49

27,11 27.11

H H

Me Me

CHMe2 CHMe2

54,5 54.5

66,39 66.39

7,80 7.80

25,81 25.81

66,07 66.07

7,77 7.77

25,57 25.57

H H

Et Et

CHMeEt CHMeEt

66,2 66.2

68,20 68.20

8,42 8.42

23,39 23.39

68,11 68.11

8,54 8.54

23,37 23.37

H H

Me Me

CMe3 CMe3

43,0 43.0

64,67 64.67

8,27 8.27

23,64 23.64

65,72 65.72

8,34 8.34

23,60a) 23.60a)

H H

Cl Cl

Cl Cl

28,6 28.6

46,50 46.50

3,90 3.90

24,65 24.65

46,15 46.15

3,99 3.99

24,31 24.31

H H

Br Br

Br Br

39,4 39.4

34,42 34.42

3,20 3.20

18,24 18.24

34,15 34.15

3,27 3.27

18,12b) 18.12b)

H H

Cl Cl

Me Me

60,1 60.1

54,65 54.65

5,35 5.35

26,55 26.55

54,45 54.45

5,32 5.32

26,33 26.33

Et Et

Me Me

Me Me

42,9 42.9

66,39 66.39

7,80 7.80

25,81 25.81

66,15 66.15

7,86 7.86

25,72 25.72

a) berechnet für Ci6H23N5 ■ 0,25 H20 • 0,20 MeOH. NMR-Spektrum bestätigt das Vorhandensein und den Anteil an MeOH. Karl Fisher Analyse: 1,49% H20. a) calculated for Ci6H23N5 ■ 0.25 H20 • 0.20 MeOH. NMR spectrum confirms the presence and proportion of MeOH. Karl Fisher analysis: 1.49% H20.

b) berechnet für CnHnBr^N, • 0,6 H20. Karl Fisher Analyse: 2,9% H20. b) calculated for CnHnBr ^ N, • 0.6 H20. Karl Fisher analysis: 2.9% H20.

"4 Z+a R R N "4 Z + a R R N

oder deren Salze, worin 10 or their salts, in which 10

R4 und R4a gleich oder verschieden sind und je ein Wasserstoffatom oder eine C^-Alkylgruppe, R4 and R4a are the same or different and each represents a hydrogen atom or a C 1-4 alkyl group,

R5 Halogen, C^-Alkyl oder C^-Alkoxy und R6 Halogen, Cw-Alkyl oder CM-Alkoxy bedeuten, das dadurch gekennzeichnet ist, dass man eine Verbindung 15 der Formel IV R5 is halogen, C ^ -alkyl or C ^ -alkoxy and R6 is halogen, Cw-alkyl or CM-alkoxy, which is characterized in that a compound 15 of the formula IV

r5 r5

^t (iv) ^ t (iv)

u u

R HN R HN

-<o> - <o>

20 20th

25 25th

worin wherein

R4, R5 und R6 wie oben definiert sind mit 2,4-Diamino-5-hydroxymethyl-pyrimidin oder einem entsprechenden Cw-Äther umsetzt, R4, R5 and R6 are as defined above reacted with 2,4-diamino-5-hydroxymethyl-pyrimidine or a corresponding Cw ether,

und anschliessend gegebenenfalls eine Verbindung der Formel III, worin and then optionally a compound of formula III, wherein

R4a Wasserstoff bedeutet, zu einer Verbindung der Formel III, worin R4a is hydrogen, to a compound of formula III, wherein

R4a Cj^-Alkyl bedeutet, N-alkyliert wird. R4a Cj ^ alkyl means N-alkylated.

30 30th

M M

Claims (2)

658 246 658 246 2 2nd PATENTANSPRÜCHE 1. Verfahren zur Herstellung einer Verbindung der Formel PATENT CLAIMS 1. Process for the preparation of a compound of the formula III III 4 4 R R 4 4 R R { O {O (IV) (IV) worin wherein R4 Wasserstoff oder C^-Alkyl, R4 is hydrogen or C 1-4 alkyl, R4a Wasserstoff, und R4a is hydrogen, and R5 und R6 gleich oder verschieden sind und je Halogen, Ci_4-Alkyl oder Cw-Alkoxy bedeuten, R5 and R6 are the same or different and each represent halogen, Ci_4-alkyl or Cw-alkoxy, dadurch gekennzeichnet, dass man eine Verbindung der Formel IV characterized in that a compound of formula IV 4 4th R HN R HN \v (IV) \ v (IV) & & mit 2,4-Diamino-5-hydroxymethylpyrimidin umsetzt. reacted with 2,4-diamino-5-hydroxymethylpyrimidine. 10 4. Verfahrennach einem der Ansprüche 1 und3, dadurch gekennzeichnet, dass man die Umsetzung in Gegenwart einer Säure durchführt. 4. The method according to one of claims 1 and 3, characterized in that one carries out the reaction in the presence of an acid. 5. Verfahren nach einem der Ansprüche 1,3 und 4, dadurch gekennzeichnet, dass man als Säure Chlorwasserstoff, Essigsäure, Methansulfonsäure oder p-ToluolsuIfonsäure verwendet. 5. The method according to any one of claims 1,3 and 4, characterized in that the acid used is hydrogen chloride, acetic acid, methanesulfonic acid or p-toluenesulfonic acid. 6. Verfahren nach Anspruch 4 oder 5, dadurch gekennzeichnet, dass man als Säure Chlorwasserstoff verwendet. 6. The method according to claim 4 or 5, characterized in that hydrogen chloride is used as the acid. 7. Verfahren nach Anspruch 4 oder 5, dadurch gekennzeichnet, dass man als Säure Methansulfonsäure oder p-Toluolsulfon-säure verwendet. 7. The method according to claim 4 or 5, characterized in that the acid used is methanesulfonic acid or p-toluenesulfonic acid. 20 20th 15 15 mit 2,4-Diamino-5-hydroxymethyl-pyrimidin oder einem entsprechenden C^-Äther umsetzt. with 2,4-diamino-5-hydroxymethyl-pyrimidine or a corresponding C ^ ether. 2. Verfahren zur Herstellung einer Verbindung der Formel 2. Process for the preparation of a compound of the formula III r4r4*n III r4r4 * n
CH6481/82A 1981-11-09 1982-11-08 METHOD FOR PRODUCING SUBSTITUTED 2,4-DIAMINO-5-BENZYLPYRIMIDINES. CH658246A5 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US31964381A 1981-11-09 1981-11-09

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CH658246A5 true CH658246A5 (en) 1986-10-31

Family

ID=23243118

Family Applications (4)

Application Number Title Priority Date Filing Date
CH6481/82A CH658246A5 (en) 1981-11-09 1982-11-08 METHOD FOR PRODUCING SUBSTITUTED 2,4-DIAMINO-5-BENZYLPYRIMIDINES.
CH4395/86A CH664960A5 (en) 1981-11-09 1982-11-08 METHOD FOR PRODUCING SUBSTITUTED 2,4-DIAMINO-5-BENZYLPYRIMIDINES.
CH4394/86A CH664959A5 (en) 1981-11-09 1982-11-08 METHOD FOR PRODUCING SUBSTITUTED 2,4-DIAMINO-5-BENZYLPYRIMIDINES.
CH4396/86A CH664961A5 (en) 1981-11-09 1982-11-08 INTERMEDIATE PRODUCTS FOR THE SYNTHESIS OF SUBSTITUTED 2,4-DIAMINO-5-BENZYLPYRIMIDINES.

Family Applications After (3)

Application Number Title Priority Date Filing Date
CH4395/86A CH664960A5 (en) 1981-11-09 1982-11-08 METHOD FOR PRODUCING SUBSTITUTED 2,4-DIAMINO-5-BENZYLPYRIMIDINES.
CH4394/86A CH664959A5 (en) 1981-11-09 1982-11-08 METHOD FOR PRODUCING SUBSTITUTED 2,4-DIAMINO-5-BENZYLPYRIMIDINES.
CH4396/86A CH664961A5 (en) 1981-11-09 1982-11-08 INTERMEDIATE PRODUCTS FOR THE SYNTHESIS OF SUBSTITUTED 2,4-DIAMINO-5-BENZYLPYRIMIDINES.

Country Status (5)

Country Link
JP (4) JPS5888368A (en)
CH (4) CH658246A5 (en)
DE (1) DE3241134C2 (en)
FR (1) FR2516081B1 (en)
GB (3) GB2109375B (en)

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE323746C (en) 1919-10-30 1920-08-04 Huebner Johannes Fire protection apparatus for cinematographic projection apparatus
GB1401612A (en) * 1971-04-16 1975-07-16 Wellcome Found 2,4-diamino-5-benzylpyrimidines and preparations thereof
AT323746B (en) * 1971-04-16 1975-07-25 Wellcome Found METHOD FOR PRODUCING NEW 2,4-DIAMINO-5-BENZYLPYRIMIDINES OR THEIR SALT
CH592066A5 (en) * 1973-02-26 1977-10-14 Hoffmann La Roche
US3923807A (en) * 1973-09-10 1975-12-02 Takeda Chemical Industries Ltd 6-Aminouracil derivatives
CH591456A5 (en) * 1973-09-12 1977-09-15 Hoffmann La Roche
US4008236A (en) * 1975-07-31 1977-02-15 Abbott Laboratories 2,4-Diamino-5-benzylpyrimidines
JPS5353385A (en) * 1976-10-26 1978-05-15 Seiko Epson Corp Clocking device
GR71725B (en) * 1977-11-10 1983-06-22 Hoffmann La Roche
CH639273A5 (en) * 1978-09-12 1983-11-15 Hoffmann La Roche DIURETIC MEANS.

Also Published As

Publication number Publication date
JPH07606B2 (en) 1995-01-11
GB2109375B (en) 1986-08-06
JPH0549665B2 (en) 1993-07-26
JPH069576A (en) 1994-01-18
GB2109375A (en) 1983-06-02
GB8515932D0 (en) 1985-07-24
JPS5888368A (en) 1983-05-26
CH664960A5 (en) 1988-04-15
GB2161805A (en) 1986-01-22
CH664961A5 (en) 1988-04-15
GB2161805B (en) 1986-07-30
GB2161158A (en) 1986-01-08
GB8515931D0 (en) 1985-07-24
DE3241134C2 (en) 1996-04-11
GB2161158B (en) 1986-07-30
FR2516081B1 (en) 1987-05-29
JPH08188574A (en) 1996-07-23
DE3241134A1 (en) 1983-05-19
JPH09227530A (en) 1997-09-02
JP2657150B2 (en) 1997-09-24
CH664959A5 (en) 1988-04-15
FR2516081A1 (en) 1983-05-13

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