IE47469B1 - Pharmaceutical preparations - Google Patents
Pharmaceutical preparationsInfo
- Publication number
- IE47469B1 IE47469B1 IE212978A IE212978A IE47469B1 IE 47469 B1 IE47469 B1 IE 47469B1 IE 212978 A IE212978 A IE 212978A IE 212978 A IE212978 A IE 212978A IE 47469 B1 IE47469 B1 IE 47469B1
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- signifies
- halogen
- hydrogen
- trifluoromethyl
- formula
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Description
The present invention is concerned with pharmaceutical preparations containing a urea derivative of the general formula
in which R1 represents halogen, trifluoromethyl, nitro 2 or lower alkoxy, R represents hydrogen, halogen, tri0 fluoromethyl, nitro or lower alkoxy and R represents 12 8 hydrogen, halogen or trifluoromethyl, R , R and R being in the meta-position or para-position relative to the
1 10 residue R and R being other than hydrogen when R is halogen, trifluoromethyl or lower alkoxy; and wherein R represents a group of the formula CH,
I 3 —NH—CO—NH—C—COOR or / » CH, (a) 3 wherein R represents lower alkyl, X 4 oxygen or imino, R represents lower
alkyl and R represents hydrogen or lower alkyl, with the proviso that a
(A) where R signifies hydrogen and R signifies the
L· κ group (b) with R and R = methyl,
R1 represents halogen, trifluoromethyl or lower alkoxy and R represents hydrogen, halogen, trifluoromethyl or lower alkoxy;
(B) where R signifies the'group (b) and the residue
ΐί represents hydrogen or C2-C^ alkyl.
The expression lower alkyl and the expression lower alkoxy relate to straight-chain or branched hydro15 carbon residues with up to 4 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec.-butyl and t-butyl; and methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec.-butoxy and t-butoxy.
Halogen signifies all four halogen atoms, i.e. fluorine.
chlorine, bromine or iodine.
?
The substituent R or R is preferably in the 3o position or 4-position and the substituent R is preferably in the 5-position.
47468
The novel preparations in accordance with the invention have an antiandrogenic action; they can accordingly be used as medicaments, in particular for the treatment of diseases associated with increased androgenic activity, such as, e.g., acne, seborrhoea, hirsutism and adenoma of the prostate.
Preferred antiandrogenically active preparations contain a compound of the formula I wherein R represents a group (b), especially such a group with X = oxygen, i.e. a hydantoin derivative of the formula I. Those antiandrogenically active preparations containing compounds of the formula I in which R1 signifies chlorine, fluorine or trifluoromethyl, R signifies hydrogen, chlorine, fluorine 3 8 or trifluoromethyl, R signifies methyl, R signifies hydro15 gen, chlorine, fluorine or trifluoromethyl and R signifies 5,5-dimethyl-3-hydantoyl are likewise preferred.
Especially preferred compounds, because of their antiandrogenic actions, are:
3-(3,4-Dichloro-phenyl)-5,5-dimethyl-hydantoin;
N-[(3-TFifluoromethyl-4-chlorophenyl)-2-carbamoyl]-2-methylalanine methyl ester.
Some of the preparations in accordance with the invention are schistoscmicidally active and can accordingly be used as medicaments for the prevention and therapy of bilharzioses. These preparations are those which contain, as the active compound, a urea derivative of the formula I in which R1 represents halogen, trifluoromethyl or nitro,
R represents hydrogen, halogen, trifluoromethyl or nitro,
8
R and R represent methyl and R represents hydrogen.
Preferred schistosomicidally active preparations »7 i69 contain a compound of the formula I wherein R represents a group (b), in particular such a group with X = oxygen, i.e.
a hydantoin derivative of the formula I. Those schisto somicidally active preparations containing'compounds of the formula I in which R1 signifies chlorine, fluorine or triο fluoromethyl, R signifies hydrogen, chlorine, fluorine or » A trifluoromethyl, R-' signifies methyl, R signifies hydrogen and R signifies 5,5-dimethyl-3-hydantoyl are likewise preferred.
lo Especially.preferred, because of their schistosomicidal action, are:
3-(3,4-Dichloro-phenyl)-5.5-dimethyl-hydantoin;
KT-[(3-Trifluoromethyl-4-chloro-phenyl)-carbamoyl -methyl-alanine methyl ester,
The preparations in accordance with the invention can be obtained using manufacturing methods customary in pharmacy. For this purpose, the active substance of the formula I is mixed with a pharmaceutical organic or inorganic carrier material suitable for enteral or parenteral administration, such as gelatin, lactose, starch, gum arabic, magnesium stearate, talc, vegetable oils, polyalkylene glycols or Vaseline (trade mark). The preparations can be in the solid form, e.g. as tablets or dragees, or in the liquid form, e.g. as solutions, suspensions or an emulsion.
They can contain adjuvants, such as preserving, stabilising, wetting or emulsifying agents, salts for varying the osmotic pressure or buffers. Other therapeutically active substances can also be admixed.
Appropriate pharmaceutical dosage forms contain about 10-500 mg of a compound of the formula I.
The dosage is chosen according to the individual requirements. For example, these compounds can be admin5 istered in dosages from 0.1 mg/kg to 50 mg/kg p.o. daily.
Dosage forms which can be used as antiandrogenio agents appropriately contain 10-500 mg, preferably about 100 mg, of a compound of the formula X. The dos10 age is, for example, o.l mg/kg to 10 mg/kg p.o.
daily, preferably about 1 mg/kg p.o. daily. This gives doses appropriately administered daily for 3-8 months, depending on the condition of the patient.
Dosage forms which can be used as schistosomioidal agents appropriately contain 100-500 mg, preferably about 250 mg, of a compound of the formula I. The dosage is, for example, 5 mg/kg to 50 mg/kg p.o. Gaily, preferably 25 mg/kg p.o. daily. This amount can be administered in a single dosage or in several sub-divided dosages, according to the requirements of the patient and the instructions of the expert. This dose is appropriately administered on one day or on several successive days, according to the condition of the patient.
The antiandrogenio action of the preparations in accordance with the invention can be demonstrated by the following test:
mg per kg of the preparation to be investigated, together with 0.5 mg per kg of testosterone propionate are administered s.c. daily to each of a group of 5 male, sterilised rats over 7 days. 3 control groups of 5 rats
Ί each received no treatment, only the preparation or only testosterone propionate respectively. The decrease in weight in the ventral prostate and the seminal vesicle is a measure of the antiandrogenic action.
Table I below provides information on some test results. ''
Table I
Compound Ventral prostate mg Seminal vesicle mg Control 17-2 25-2 Testosterone propionate 14O±11 88±5 3-(3,4-Dichlorophenyl)-5,5-dimethylhydantoin + testosterone propionate 36^4 29-2 15 Control 14±1 2^2 Testosterone propionate 121-13 100-9 N-[(3-Trifluoromethyl-4-chlorophenyl)carbamoyl]-2-methylalanine methyl ester + testosterone propionate 61±6 47±11
The schistosomicidal action of the preparations in accordance with the invention can be seen, for example, from the following test:
Mice are infected subcutaneously with 60 cercariae of Schistosoma mansoni. 42 days after the infection, the animals are treated perorally once or (in a further test) on 5 successive days with the preparations to be tested.
-10 animals are used per preparation and dosage (mg/kg).
untreated animals serve as the control. The autopsy is carried out 6 days or 2-3 weeks after conclusion of the treatment. Worm pairs in mesenteric veins, the portal vein and the liver are dissected out and counted. The percentage distribution of the worm pairs in mesenteric veins, the portal vein and the liver is calculated and the condition of the worms (living or dead) is recorded. The action of the preparation is manifested in an increased proportion of worms in the vessels of the liver and in the appearance of dead worms.
For the evaluation, the percentage proportion of living and dead worm pairs in the -vessels of the liver both in infected treated animals and in infected but untreated lo control animals is compared. The determination of the TO50 (vermicidal dose 50%: the dose which kills 50% of the worm pairs) is carried out by the Probit method.
Some test results are summarised in Table II below:
Table II
CompoundTO50 mg/kg p.o. (administered 5 times) 20 N-[(3-Trifluoromethyl-A—chloro-phenyl)oarbamoyl]-2-methylalanine methyl ester 74 5-(3,4-Dichloro-phenyl)-5,5-dimethyllydantoin 58
The toxic action in mice (observed after 24 hours) was likewise determined and can be seen from Table III below:
♦ 7 4 6 8
Tah^e III
CompoundLDS0 mg/kg p.o. N-/T3-Trifluoromethyl-4-chloro-phenyl)carbarooyl7-2-methylalanine methyl ester 5000 5 3-(3,4-Dichloro-phenyl)-5,5-dimethylhydantoin 2500-5000
Some of the urea derivatives of the formula I are novel compounds and are the subject of Patent Specification No. 47470
The urea derivatives of the formula I can be manufactured in accordance with one of the following processes when
a) to manufacture a compound of the formula la in which Ra represents the group (a), a compound of the general formula
is reacted under anhydrous conditions with a compound of the general formula
CHI 3 III
X2—C—COOR
8 3 in which R , R , R and R have the above significance and one of the symbols X^ and X2 represents amino and the other represents the iso-cyanate group -NCO, or when
b) to manufacture a compound of the formula I in which R represents the group (a), a compound of the general formula
β 7 given above and R and R'both represent lower alkyl, is subjected to alcoholysis using an alcohol of the formula
R^OH, wherein R^ has the above significance, or when
c) to manufacture a compound of the formula I in which R signifies the group (b ) with X = oxygen, a compound of the general formula
significance and Y represents the group -OR^ or 6 7 6 7
-NR R', wherein R° and R' have the above significance and R^° represents hydrogen or lower alkyl, is cyclised, or. when
d) to manufacture a compound of the formula I in v/hich R signifies the group (b ) with X = imino, a compound of the general formula ·%: \\
-NCO
VI
RS
4746©
TO Q in which R , R and R have the above significance, is reacted under anhydrous conditions with a compound of the general formula
R4
CN
VII
L· 5 in which R and R have the above significance, or when
Q
e) to manufacture a compound of the formula Ia in which R signifies the group (b ) with X = oxygen, a compound of the general formula
significance, is subjected to hydrolysis, or when
f) to manufacture a compound of the formula Ia in which R 15 represents the group (a), a compound of the general formula
given above, is esterified with compounds which supply lower alkyl groups , or when
g) to manufacture a compound of the formula Ia in which 1 2
R and/or R represents nitro, a compound of the formula
Id in which R and R have the significance given above and R^° and R20 have the significances given 1 2 above for R and R , but at least one of the symbols R^ and R2® representing hydrogen, is nitrated.
The anhydrous reaction of the starting compounds of the formulae II and III leads to compounds of the formula I in which R represents the group (a). This addition reaction can be carried out without the addition of solvents, i.e. by means of a melt, or also by warming in an inert, anhydrous solvent, e.g. tetrahydrofuran, ether, dioxan, benzene or toluene. The temperature for the reaction is preferably in the range of 0°-120°C. If the reaction is carried out in a melt, it must be noted that relatively high temperatures or relatively long reaction times lead to cyclisation, with form47 46S ation of the corresponding hydantoin (c.f. hereinafter).
The reaction should therefore be interrupted in time, which can be accomplished, for example, by monitoring by thin-layer chromatography.
The starting compounds of the formula IV can be manufactured by reacting a substituted benzhydroxamic acid of the general formula
with an azirine derivative of the general formula
7 in which R and R have the significance given above.
The reaction proceeds successfully in an inert solvent, such as tetrahydrofuran, ether or dioxan, at room temperature or with slight warming, e.g. to 50°C.
The alcoholysis of the starting amides of the formula IV is carried out with the aid of a lower alkanol, preferably methanol or ethanol, and leads to carboxylic acid esters of the formula I wherein R .represents the group (a). The alcoholysis is preferably carried out under acid, e.g. mineral acid, conditions, for example in methanolic or ethanolic hydrochloric acid.
The reaction temperature is preferably about room temperature but, if desired, it can be increased up to the boiling temperature of the reaction mixture.
The manufacture of the starting amides or esters of the formula V can be carried out analogously to the manufacture of the amides of the formula IV or of the esters of the formula la, from the compounds II and III. For the manufacture of a carboxylic acid of the formula V, an amide of the formula V can be dissolved in an inert organic solvent, e.g. methanol or ethanol, and the solution can be treated with an aqueous alkali, e.g, caustic soda solution or caustic potash solution, at a temperature between room temperature and the boiling point of the reaction mixture. The corresponding carboxylic acid of the formula Ia is obtained in the customary manner by neutralisation of the carboxylic acid salt formed, for example using a mineral acid.
The cyclisation of the startinq amides or esters of the formula V leads to hydantoin derivatives of the formula I , and in particular those wherein R signifies the group (b ) with X = oxygen. This cyclisation is carried out, e.g. under the conditions of acid hydrolysis, preferably by treatment with an aqueous mineral acid, such as aqueous hydrochloric acid. The , acid hydrolysis of amides of the formula V is advantageously carried out in an inert organic solvent, e.g. tetrahydrofuran or dioxan, and at about room temperature, it also being possible to carry out the hydrolysis at higher temperatures, e.g. up to the boiling point of the reaction
469 mixture. The cyclisation of esters of the formula V is preferably carried out with a water-miscible solvent, such as acetone, methyl ethyl ketone, tetrahydrofuran, dimethoxyethane or dioxan. A preferred cyclisation .
agent consists of 6-N aqueous hydrochloric acid and acetone in a weight ratio of about 1:1. The reaction temperature is preferably the boiling temperature of the reaction mixture, it also being possible to use lower reaction tempera tures, e.g. down to room temperature, with appropriately longer reaction times. The starting esters of the formula V can likewise be cyclised by warming without solvents, i.e. by means of a melt. The temperature for this melt reaction is preferably in the range of about 100-200°C, in particular in the range of about 12O~16Q°C.
Preferably, this -cyclisation is carried out by adding - the compounds of the above formula II and III which can be used for the manufacture of the starting esters of the formula V, and by choosing an adequate reaction time or reaction temperature, the reaction proceeds to the desired cyclisation product, i.e. the’ hydantoin of the formula Ia, without isolating the esters of the formula V intermediately formed. The reaction can be followed, for example, by thin-layer chromatography.
The anhydrous reaction of the starting compounds of the formulae VI and VII leads to imino-imidazolidinone derivatives of the formula I ,
i.e. wherein R signifies the group (b ) v/ith X = imino.
The reaction can be carried out under the same conditions as the cyclisation described above, using starting compounds of the .formulae II and III, i.e. by means of a melt. It is
4746a also possible to heat the starting compounds of the formulae II and III with an ethereal solvent, e.g. with dioxan or dimethoxyethane.
The hydrolysis of the imino-imida5 zolidinone derivatives of the formula lb leads to corresponding hydantoins of the formula Ia, i.e. wherein R signifies the group (b ) with X‘ = oxygen. The hydrolysis can be carried out, optionally with the addition of an inert solvent, by treatment with, e.g., a mineral acid, io such as hydrochloric acid, at a temperature between room temperature and the boiling point of the reaction mixture.
The esterification of 'the carboxylic acid of the formula Ic leads to esters of the formula I wherein R represents the group (a). The esterification is carried out in a manner known per se by treatment with a lower alkanolic mineral acid, e.g. methanolic hydrochloric acid, with a lower alkyl halide, e.g. methyl iodide, and an alkali metal carbonate or bicarbonate in a solvent, such as dimethylformamide, or with diazomethane in an ethereal solvent, such as ether, tetrahydrofuran or dioxan. The esterification temperature is in general in the range o-5o°c.
The nitration of the compounds of the formula Id leads to riitro derivatives of the 1 2 formula I wherein R and/or R represent nitro. Por this purpose, the compound of the formula Id is nitrated in a manner known per se. e.g. by treatment with nitric acid, with nitric acid and sulphuric acid, with nitric acid and glacial acetic acid or acetic acid anhydride or with an alkali metal nitrate and sulphuric acid. The nitration
469 is preferably carried out at a low temperature, for example at about 0°C to room temperature.
Other compounds of the formula I are manufactured in a completely analogous manner to that-described above.
Some of the compounds of the formula I are crystalline, solid substances which have.a relatively good solubility in lower alkanols, such as methanol or ethanol, dimethyl sulphoxide, dimethylformamide and hexamethylphosphoric acid triamide, and in some cases also in chlorinated lo hydrocarbons, such as chloroform, methylene chloride and carbon tetrachloride, and are relatively sparingly soluble in ether, benzene and water.
Example 1
Manufacture of tablets of the following composition:
Active substance of the formula I 100.0 mg
Lactose 40.0 mg
Maize starch 3^.0 mg
Ethyl cellulose 4.0 mg
Talc 1.8 mg
Magnesium stearate 0.2 mg
180.0 mg
The active substance is mixed with the lactose and the maize starch and the mixture is granulated with a solution of the ethyl cellulose in 16 ml of methylene chloride.
The granulate is dried at 40°C, mixed with the talc and magnesium stearate and pressed to tablets.
Weight of one tablet 180 mg
Active substance content of one tablet 100 mg
Example 2
Manufacture of tablets of the following composition:
Active substance of the formula I 250.0 mg Lactose 100.0 mg Maize starch 85.0 mg Ethyl cellulose 10.0 mg Talc 4.5 mg Magnesium stearate 0.5 mg
450.0 mg
The active substance is mixed with the lactose and the maize starch and the mixture is granulated with a solution of the ethyl cellulose in 40 ml of methylene chloride. The granulate is dried at 4o°C, mixed with the talc and magnesium stearate and pressed to tablets.
Weight of one tablet 450 mg
Active substance content of one tablet 250 mg Example 5
Manufacture of capsules Active substance of the
Lactose
Maize starch
Talc of the following composition: formula I 100.0 mg
62.0 mg 12.0 mg 6.0 mg
180.0 mg
The active substance is homogeneously mixed with the lactose and the maize starch, the mixture is passed through a sieve machine and, after intermixing of the talc, filled into gelatin capsules
Weight of filling in capsule Active substance content
180 mg
100 mg
Example 4
Manufacture of capsules of the following composition:
Active substance of the formula I 250.0 mg 5 Lactose 155.0 rag Maize starch 30.0 mg Talc 15.0 mg
450.0 mg
The active substance is homogeneously mixed with 10 the lactose and the maize starch, the mixture is passed through a sieve machine and, after intermixing of the talc, filled into gelatin capsules.
Weight of filling in capsule 450 mg
Active substance content 250 mg
Example 5
9.75 g (50 mmol) of 5-amino-2-chlorobenzotrifluoride and 7.15 g (50 mmol) of 2-isocyanato-2-methylpropionic acid methyl ester are melted at 80°C and the melt is kept at this temperature for 30 minutes. The product which has crystallised out during this process is recrystallised from isopropanol/methylene chloride and dried under greatly reduced pressure at 50° for 20 hours. Ν-/Ϊ 3-Trifluoromethyl -4-chlorophenyl)-carbamoyl7-2-methylalanine methyl ester, which melts at 141142°, is obtained.
Analysis:
Calculated for C13H14C1F3N2O3 (338.71):
C 46.10 H 4.17 N 8.27% Found: C 46.17 H 4.14 N 8.26% The following compound is obtained in the same
manner:
N-/73-Nitro-4-chlorophenyl)-carbamoyl7-2-methylalanine methyl ester (in the melt at 100° for 30 minutes); m.p. 142-143°C.
Example 6
A solution of 17.2 g (67.5 mmol) of N-/(3,4dichlorophenyl)-carbamoyl/-2-methylalanine methyl ester in 150 ml of 6-N aqueous hydrochloric acid and 50 ml of acetone are warmed on a steam bath for 2 hours and the mixture is then concentrated. The product which has pre20 cipitated is first dried at 4O°/15 Torr and then recrystallised from toluene. After drying under greatly reduced pressure at 50° for 20 hours, 3-(3,4-dichlorophenyl)-5,5dimethylhydantoin of melting point 166-167° is obtained.
*7469
Example 7
A mixture of 2.91 g (20 mmol) of 3-chloro-4-fluoroaniline and 3.01 g (21 mmol) of 2-isocyanato-propionic acid ethyl ester is kept at 130-140° for 9i hours. After crystallisation from chloroform/methanol, 3-(5-chloro-4-fluorophenyl)-5-methyl-hydantoin of m.p. 174-175.5° is obtained.
Analysis:
Calculated for C10H8ClFN202 (242.64):
C 49.50 H 3.32 N 11.55 Cl 14.61%
Found: C 49.49 H 3.18 N 11.51 Cl 14.82%
Example 8
6.65 g (30 mmol) of 4-chloro-3-trifluoromethylphenylisooyanate and 4.4 g (30 mmol) of 2-amino-2-ethyl-butyric acid methyl ester are heated to 100° for 5 minutes. The crude product, 2-(N-[(4-chloro-3-trifluoromethylphenyl)carbamoyl]-amino-2-ethyl-butyric acid methyl ester), is heated in 200 ml of acetone and 600 ml of 6-N HCl on a steam bath for 8 hours. After cooling, the mixture is extracted with methylene chloride and the extract is dried over sodium sulphate and evaporated. After crystallisation of the residue from petroleum ether and from methylene chloride/ hexane, 3-(4-chloro-3-trifluoromethylphenyl)-5,5-diethylhydantoin of melting point 36-87° is obtained.
Analysis:
Calculated for C14H14C1F3N2°2 (334.72):
C 50.24 H 4.22 H 8.37%
Found: C 50.40 H 4.34 N 8.27%
Claims (10)
1. Pharmaceutical preparation containing a urea derivative of the general formula in which o R represents hydrogen, halogen, trifluoromethyl, nitro or lower alkoxy and R® represents hydrogen, halogen or trifluoromethyl, TO ft R , R and R being in the meta-position or parapasitian relative to the residue R and R 3 being other than hydrogen when R 1 is halogen, trifluorcnethyl or lower alkoxy; and wherein R represents a group of the formula nitro or lower alkoxy, wherein R^ represents lower alkyl, X represents 4 5 15 oxygen or imino, R represents lower alkyl and R represents hydrogen or lower alkyl, with the proviso that ft (A) where R signifies hydrogen and R signifies the , . 4 ς group (b) with R and R = methyl, 20 R represents halogen, trifluoromethyl or lower o alkoxy and R represents hydrogen, halogen, trifluoromethyl or lower alkoxyj (B) where R signifies the group (b) and the residue 4*1 5 with a pharmaceutically acceptable carrier.
2. Preparation according to claim 1, wherein R 1 signifies chlorine, fluorine or trifluoromethyi, R signifies hydrogen, chlorine, fluorine or trifluoromethyi, 3. 8 R signifies methyl, R signifies hydrogen, chlorine, fluor10 Ine or trifluoromethyi and R signifies 5,5-dimethy1-3-hydantoyl.
3. Preparation according to claim 1, wherein R 1 represents halogen, trifluoromethyi or nitro, R represents hydrogen, halogen, trifluoromethyi or nitro, 15 R 4 and R 3 represent methyl, R 3 represents hydrogen and R is one of the groups (a) and (b).
4. Preparation according to claim 3, wherein R 1 signifies chlorine, fluorine or trifluoromethyi, R signifies hydrogen, chlorine, fluorine or trifluoromethyi, 3 8 20 R signifies methyl, R signifies hydrogen and R signifies 5. ,5-dimethyl-3-hydantoyl.
5. Preparation according to claim 3, containing 3-(3,4-dichloro-phenyl)-5,5-dimethyl-hydantoin.
6. Preparation according to claim 3, containing 5 N-273-trifluoromethy1-4-chlorophenyl)-carbamoyl7-2-methylalanine methyl ester.
7. Process for the manufacture of a pharmaceutical preparation, wherein a urea derivative of the general formula I set out in claim 1 as the active constituent 10 is mixed with a non-toxic, inert, solid or liquid carrier and/or excipient which is suitable for therapeutic administration and is suitable per se in such preparations.
8. Urea derivatives of the general formula 15 in which R 1 represents halogen, trifluoromethyl, nitro or lower alkoxy, R represents hydrogen, halogen, trifluoromethyl, nitro or lower alkoxy and p R represents hydrogen, halogen or trifluoromethyl, T 2 8 R , R and R being in the meta-position or para2 20 position relative to the residue R and R being other than hydrogen when R 1 is halogen, trifluoromethyl or lower alkoxy; and wherein R represents 47 463 -ΐ' a group of the formula CH, I 3 —-NH—CO—-NH—C—COOR ' or (a) CH, NH (b) wherein R represents lower alkyl, X represents 4 oxygen or imino, R represents lower alkyl and R represents hydrogen or lower alkyl, with the proviso that Q (A) where R signifies hydrogen and R signifies 4 5 the group (b) with R and R = methyl, R^ represents halogen, trifluoromethyl or lower 2 alkoxy and R represents hydrogen, halogen, trifluoromethyl or lower alkoxy; (B) where R signifies the group (b) and the residue signifies one
9. Drea derivatives according to claim 8, wherein
10. 1 2 R represents halogen, trifluoromethyl or nitro, R represents hydrogen, halogen, trifluoromethyl or nitro, R 4 and R 5 represent methyl and R 8 represents hydrogen, for use as schistosomicidally active agents.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IE212978A IE47469B1 (en) | 1978-10-27 | 1978-10-27 | Pharmaceutical preparations |
IE2809/82A IE47470B1 (en) | 1978-10-27 | 1978-10-27 | Urea derivatives |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IE212978A IE47469B1 (en) | 1978-10-27 | 1978-10-27 | Pharmaceutical preparations |
Publications (2)
Publication Number | Publication Date |
---|---|
IE782129L IE782129L (en) | 1979-04-28 |
IE47469B1 true IE47469B1 (en) | 1984-03-21 |
Family
ID=11032976
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IE212978A IE47469B1 (en) | 1978-10-27 | 1978-10-27 | Pharmaceutical preparations |
IE2809/82A IE47470B1 (en) | 1978-10-27 | 1978-10-27 | Urea derivatives |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IE2809/82A IE47470B1 (en) | 1978-10-27 | 1978-10-27 | Urea derivatives |
Country Status (1)
Country | Link |
---|---|
IE (2) | IE47469B1 (en) |
-
1978
- 1978-10-27 IE IE212978A patent/IE47469B1/en unknown
- 1978-10-27 IE IE2809/82A patent/IE47470B1/en unknown
Also Published As
Publication number | Publication date |
---|---|
IE47470B1 (en) | 1984-03-21 |
IE822809L (en) | 1979-04-28 |
IE782129L (en) | 1979-04-28 |
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