CA1055498A - 2,4-diamino-5-benzylpyrimidines, process for their preparation and pharmaceutical compositions containing these compounds - Google Patents
2,4-diamino-5-benzylpyrimidines, process for their preparation and pharmaceutical compositions containing these compoundsInfo
- Publication number
- CA1055498A CA1055498A CA262,152A CA262152A CA1055498A CA 1055498 A CA1055498 A CA 1055498A CA 262152 A CA262152 A CA 262152A CA 1055498 A CA1055498 A CA 1055498A
- Authority
- CA
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- Prior art keywords
- acid
- diamino
- benzylpyrimidine
- chemical equivalent
- obvious chemical
- Prior art date
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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
- C07D239/46—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
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
New 2,4-diamino-5-benzylpyrimidines, process for their preparation and pharmaceutical compositions containing these compounds.
New 2,4-diamino-5-benzylpyrimidines, process for their preparation and pharmaceutical compositions containing these compounds.
Description
~55~9~
This invention relates to new benzylpyrimidines, to a process for their preparation and to pharmaceutical compositions containing them.
In particular, the invention relates to new 2,4-diamino-5-benzylpyrimidines of the general formula R
~ C~2 ~ ~ I
32N1N; J OC33 in which R represents an alkyl group having from 1 to 4 carbon atoms or a halogen atom, and to their pharmacologically acceptable acid addition salts.
The invention also relates to a process for the preparation of such 2,4-diamino-5-benzylpyrimidines and their salts, in which 2,4-diamino-5-hydroxymethylpyrimidine of the formula ~ f H2-OH
~ N ~ II
is reacted with a methoxyphenol of the yeneral formula OH
R ~ OCH3
This invention relates to new benzylpyrimidines, to a process for their preparation and to pharmaceutical compositions containing them.
In particular, the invention relates to new 2,4-diamino-5-benzylpyrimidines of the general formula R
~ C~2 ~ ~ I
32N1N; J OC33 in which R represents an alkyl group having from 1 to 4 carbon atoms or a halogen atom, and to their pharmacologically acceptable acid addition salts.
The invention also relates to a process for the preparation of such 2,4-diamino-5-benzylpyrimidines and their salts, in which 2,4-diamino-5-hydroxymethylpyrimidine of the formula ~ f H2-OH
~ N ~ II
is reacted with a methoxyphenol of the yeneral formula OH
R ~ OCH3
- 2 -~(~55a~
in which R represents an alkyl yroup haying from 1 to 4 carbon atoms or a halogen atom, and, if desired, the resulting compound is converted into a pharmacologically acceptable acid addition salt.
In a preferred embodiment of the invention, the reaction is carried out by heating in glacial acetic acid in the presence of concentrated hydrochloric acid. A reaction of this kind has been described, for example, in German Offenlegungsschrift No. 2,249,532.
The invention further provides a process for the preparation of such 2,4-diamino-5-benzylpyrimidines, in which a hydrocinnamic acid ester of the general formula R
in which R represents an alkyl yroup haying from 1 to 4 carbon atoms or a halogen atom, and, if desired, the resulting compound is converted into a pharmacologically acceptable acid addition salt.
In a preferred embodiment of the invention, the reaction is carried out by heating in glacial acetic acid in the presence of concentrated hydrochloric acid. A reaction of this kind has been described, for example, in German Offenlegungsschrift No. 2,249,532.
The invention further provides a process for the preparation of such 2,4-diamino-5-benzylpyrimidines, in which a hydrocinnamic acid ester of the general formula R
3 2 ~ ~3 C~2 CH2 C 0 X IV
' .' .
in which R represcnts an alkyl group having from 1 to 4 carbon atoms or a halogcn atom and X represents an alkyl group having from 1 to 4 carbon atoms is formylated with ethyl formate in the presence of sodium, the compound obtained is condensed with guanidine in an alkaline medium and the resulting 2-amino-4-hydroxy~5-(substituted henzyl)-pyrimidine is reacted with phosphorus oxychloride and the chlorine compound thereby obtained is reacted with a~nonia and, if desired, the resulting compound is converted into its pharmacologically acceptable acid addition salt.
The invention also relates to a proc~ss for the preparation of such 2,4-diamino-5-benzylpyrimidine5 in which a ~-am.inoacrylonitrile of the formula . -.
.
~s~
CH3-0-CH2 0 _ ~ CIM V
in which R represents an alkyl group having from 1 to ~ carbon atoms or a halogen atom and R' represents an aniline group which may be substituted or a morpholine group; is reacted ~ith guanidine in alcoholic solution under conditions of heating under refluxl the alcoho] is distilled off and the product left behind after removal of the alcohol, which has the general formula N ~ C ~ ~ O-C~I -OC~ VI
~ M~J OCH3 in which R has the meaning already specified, ls heated to boiling in alcoholic hydrochloric acid so tha-t the methoxy methyl group is split off, the compound is converted into the desired 2,4-diamino-5-benzylpyrimidine compound and, if desired, this compound is then converted into a pharmacologically acceptable acid addition salt.
In the ye~e~al formula (I), the subs-tituent R repre-sents a straight or branched chain alkyl group having from 1 to 4 carbon atoms, e.g. a methyl, ethyl, M-propyl, isopropyl, n-butyl or isobutyl group. Cornpounds in which R is a methyl or ethyl group are preferred. X represents a halogen atom, 1135S4~
e.g. a chlorine, bromine or iod~ne atom. Compounds in which represents a chlorine or bromine atom are preferred.
The compounds according to the invention, represented by the general formula (I), and their salts, are new compounds.
Specific examples of pharmacologically acceptable acid addition salts include the salts of the compounds with hydro-chloric acid, hydrobromic acid, sulphuric acid, acetic acid, tartaric acid, fumaric acid, maleic acid and ascorbic acid.
The compounds according to the invention have a good antibacterial action which is comparable to and in part superior to that of the known compound, 2,4-diamino-5-(3',4',5'-trimethoxybenzyl)-pyrimidine which is also known as trimethoprim.
Their toxicity, however, is considerably lower than that of trimethoprim so that the compounds according to the invention have a better therapeutic quotient, i.e. a wider therapeutic range.
The antibacterial activity can be further improved by combining the compounds according to the invention with sulphonamides, e.g. sulphadiazine, sulphadiamidine, sulpha-methoxazole, sulphaquinoxaline, sulphadinemethoazine, sulpho-merazine and sulphamethoxydiazine.
The invention therefore also relates to a pharma-ceutical composition which, in addition to the usual auxiliary substances and excipi.ents, contains at least one of the com-pounds of the general formula (I).
For application in the dry form, the following combin-ations may be used as excipients: Cellulose, dextrose, corn starch, saccharose, talcum, magnesium stearate, calcium hydro-gen phosphate, lactose~ gelatine and polyvinyl pyrrolidine.
Suitable auxiliary agents for application in the liquid form include, for example, solutions or suspensions of carboxymethyl-1~554~
cellulose, cellulose, sorbitol, saccharose, caramel and flavourings in water. For parenteral administration, compounds of the formula (I) are suitable in the form of buffer solutions.
The invention will be further described with the aid of the following Examples.
.
Preparation of 2,4-dlamino-5-(3'-methoxy-4'-h~rdroxy-5'-methyl-benzyl)-pyrimidine and its hydrochloride -51.0 g (0.36 mol) of 2,4-diamino-5-hydroxymethyl-pyrimidine and 49.4 g (0.36 mol) of 2~methyl-6-methoxy-phenol in 3.5 1 of glacial acetic acid and 110 ml of concentrated hydrochloric acid were heated to 100C for 5 hours in a 5 1 flask. A
precipitate which formed in the ~rly stages of the reaction slowly dissolved. At the end of the reaction time, the acetic acid and hydrochloric acid were distilled off except for a residual volume of about 250 ml, 300 ml of water were added to the residue and the solution was extracted twice with 150 ml portions of chloroform. The aqueous phase was then evaporated to dryness under vacuum and the residue was stirred up with about 200 ml of acetone until a homogeneous suspension was obtained. The precipitate was suction filtered, washed with a small ~uantity of acetone and dried at 100C.
Crude yield: 85.3 g.
The salt was dissolved in hot water by conversion of the hydrochloride into the base, and the solution was carefully neutralized with saturated sodium bicarbonate solution with stirring. The greasy precipitate first formed was filtered off and a further quantity of sodium bicarbonate solution was added to the filtrate. The precipitated base was then recrystallized from 20 to 30% aqueous alcohol.
Melting point: 189 to 193C.
' .' .
in which R represcnts an alkyl group having from 1 to 4 carbon atoms or a halogcn atom and X represents an alkyl group having from 1 to 4 carbon atoms is formylated with ethyl formate in the presence of sodium, the compound obtained is condensed with guanidine in an alkaline medium and the resulting 2-amino-4-hydroxy~5-(substituted henzyl)-pyrimidine is reacted with phosphorus oxychloride and the chlorine compound thereby obtained is reacted with a~nonia and, if desired, the resulting compound is converted into its pharmacologically acceptable acid addition salt.
The invention also relates to a proc~ss for the preparation of such 2,4-diamino-5-benzylpyrimidine5 in which a ~-am.inoacrylonitrile of the formula . -.
.
~s~
CH3-0-CH2 0 _ ~ CIM V
in which R represents an alkyl group having from 1 to ~ carbon atoms or a halogen atom and R' represents an aniline group which may be substituted or a morpholine group; is reacted ~ith guanidine in alcoholic solution under conditions of heating under refluxl the alcoho] is distilled off and the product left behind after removal of the alcohol, which has the general formula N ~ C ~ ~ O-C~I -OC~ VI
~ M~J OCH3 in which R has the meaning already specified, ls heated to boiling in alcoholic hydrochloric acid so tha-t the methoxy methyl group is split off, the compound is converted into the desired 2,4-diamino-5-benzylpyrimidine compound and, if desired, this compound is then converted into a pharmacologically acceptable acid addition salt.
In the ye~e~al formula (I), the subs-tituent R repre-sents a straight or branched chain alkyl group having from 1 to 4 carbon atoms, e.g. a methyl, ethyl, M-propyl, isopropyl, n-butyl or isobutyl group. Cornpounds in which R is a methyl or ethyl group are preferred. X represents a halogen atom, 1135S4~
e.g. a chlorine, bromine or iod~ne atom. Compounds in which represents a chlorine or bromine atom are preferred.
The compounds according to the invention, represented by the general formula (I), and their salts, are new compounds.
Specific examples of pharmacologically acceptable acid addition salts include the salts of the compounds with hydro-chloric acid, hydrobromic acid, sulphuric acid, acetic acid, tartaric acid, fumaric acid, maleic acid and ascorbic acid.
The compounds according to the invention have a good antibacterial action which is comparable to and in part superior to that of the known compound, 2,4-diamino-5-(3',4',5'-trimethoxybenzyl)-pyrimidine which is also known as trimethoprim.
Their toxicity, however, is considerably lower than that of trimethoprim so that the compounds according to the invention have a better therapeutic quotient, i.e. a wider therapeutic range.
The antibacterial activity can be further improved by combining the compounds according to the invention with sulphonamides, e.g. sulphadiazine, sulphadiamidine, sulpha-methoxazole, sulphaquinoxaline, sulphadinemethoazine, sulpho-merazine and sulphamethoxydiazine.
The invention therefore also relates to a pharma-ceutical composition which, in addition to the usual auxiliary substances and excipi.ents, contains at least one of the com-pounds of the general formula (I).
For application in the dry form, the following combin-ations may be used as excipients: Cellulose, dextrose, corn starch, saccharose, talcum, magnesium stearate, calcium hydro-gen phosphate, lactose~ gelatine and polyvinyl pyrrolidine.
Suitable auxiliary agents for application in the liquid form include, for example, solutions or suspensions of carboxymethyl-1~554~
cellulose, cellulose, sorbitol, saccharose, caramel and flavourings in water. For parenteral administration, compounds of the formula (I) are suitable in the form of buffer solutions.
The invention will be further described with the aid of the following Examples.
.
Preparation of 2,4-dlamino-5-(3'-methoxy-4'-h~rdroxy-5'-methyl-benzyl)-pyrimidine and its hydrochloride -51.0 g (0.36 mol) of 2,4-diamino-5-hydroxymethyl-pyrimidine and 49.4 g (0.36 mol) of 2~methyl-6-methoxy-phenol in 3.5 1 of glacial acetic acid and 110 ml of concentrated hydrochloric acid were heated to 100C for 5 hours in a 5 1 flask. A
precipitate which formed in the ~rly stages of the reaction slowly dissolved. At the end of the reaction time, the acetic acid and hydrochloric acid were distilled off except for a residual volume of about 250 ml, 300 ml of water were added to the residue and the solution was extracted twice with 150 ml portions of chloroform. The aqueous phase was then evaporated to dryness under vacuum and the residue was stirred up with about 200 ml of acetone until a homogeneous suspension was obtained. The precipitate was suction filtered, washed with a small ~uantity of acetone and dried at 100C.
Crude yield: 85.3 g.
The salt was dissolved in hot water by conversion of the hydrochloride into the base, and the solution was carefully neutralized with saturated sodium bicarbonate solution with stirring. The greasy precipitate first formed was filtered off and a further quantity of sodium bicarbonate solution was added to the filtrate. The precipitated base was then recrystallized from 20 to 30% aqueous alcohol.
Melting point: 189 to 193C.
4~8 The hydrochloride melted at 241 to 243C.
Calculated:
C 50.98% H 5.35% Cl 12.54% N 19.82% O 11.32%
Found:
C 51.11% H 5.45% Cl 13.51% N 19.46% O 10.84%
Preparation of 2,4-diamino-5-(3'-bromo-4'-hydroxy-
Calculated:
C 50.98% H 5.35% Cl 12.54% N 19.82% O 11.32%
Found:
C 51.11% H 5.45% Cl 13.51% N 19.46% O 10.84%
Preparation of 2,4-diamino-5-(3'-bromo-4'-hydroxy-
5'-methoxy-benzyl)-pyrimidine 62.2 g of 3-bromo-4-methyl-dihydroxymethylene-5-methoxy-ben~aldehyde, 37.8 g oE anilinopropionitrile, 45 ml of dimethyl-sulphoxide and 110 ml of tert.-butanol were introduced into a 500 ml flask and heated until completely dissolved. When the solution had cooled to 10 C, 19.4 g of potassium tert.-butylate were added portionwise at such a rate that the reaction temper-ature did not rise above 25C. When all the potassium tert.-butylate had been added, the reaction mixture was heated to 40-50C for 5 hours and the tert.-butanol and dimethylsulphoxide were then distilled o~f under vacuum. The residue was taken up with 300 ml of methylene chloride and the methylene chloride layer was washed with water, dehydrated over sodium sulphate and evaporated to dryness.
The crude yield was: 28.2 g.
This quantity was heated to boiling together with 41 g of guanidine hydrochloride in 440 ml of ethanol. To the resulting solution were added dropwise 69.4 ml of a 30% sodium methylate solution over a period of 40 minutes and the mixture was then kept at boiling point for a further 6 hours. The sodium chloride precipitate was filtered off and the alcohol was distilled off. The oil left behind was taken up with a mixture of 50 ml of ethanol and 150 ml of water and acidi~ied to pH 1 1(35S~
with concentrated hydrochloric acid. The solution was gently heated to boiling and, after removal of undissolved consti-tuents, the solution was made alkaline with ammonia. The precipitate obtained was suction filtered and recrystallized from ethanol.
The melting point was 229C.
C12H13N4 O2Br Calculated:
C 44,32% H 5.03% Br 24.57% N 17.23% O 9.84%
Found:
C 44.39% H 4.37% Br 25.03% N 16.70% O 9.53%.
The crude yield was: 28.2 g.
This quantity was heated to boiling together with 41 g of guanidine hydrochloride in 440 ml of ethanol. To the resulting solution were added dropwise 69.4 ml of a 30% sodium methylate solution over a period of 40 minutes and the mixture was then kept at boiling point for a further 6 hours. The sodium chloride precipitate was filtered off and the alcohol was distilled off. The oil left behind was taken up with a mixture of 50 ml of ethanol and 150 ml of water and acidi~ied to pH 1 1(35S~
with concentrated hydrochloric acid. The solution was gently heated to boiling and, after removal of undissolved consti-tuents, the solution was made alkaline with ammonia. The precipitate obtained was suction filtered and recrystallized from ethanol.
The melting point was 229C.
C12H13N4 O2Br Calculated:
C 44,32% H 5.03% Br 24.57% N 17.23% O 9.84%
Found:
C 44.39% H 4.37% Br 25.03% N 16.70% O 9.53%.
Claims (21)
1. A process for the preparation of 2,4-diamino-5-benzylpyrimidine of the general formula I
in which R represents an alkyl group having from 1 to 4 carbon atoms or a halogen atom, said process being selected from the group consisting of:
(A) by reaction of a 2,4-diamino-5-hydroxymethylpyrimidine of the formula II
with a methoxyphenol of the formula III
wherein R is as defined above, and, if desired, con-verting the compound of formula III into a pharma-cologically acceptable acid addition salt;
(B) formylating a hydrocinnamic acid ester of the general formula IV
wherein R has the meaning specified above and X represents an alkyl group having from 1 to 4 carbon atoms, with ethyl formate in the presence of sodium, condensing the compound obtained with guanidine in an alkaline medium and reacting the resulting 2-amino-4-hydroxy-5-(substituted benzyl)-pyrimidine with phosphorus oxychloride, reacting the chlor-ine compound obtained with ammonia and, if desired, conver-ting the resulting compound into its pharmacologically acceptable acid addition salt; or (C) reacting a .beta.-amino-acrylonitrile of the formula V
in which R represents an alkyl group having from 1 to 4 carbon atoms or a halogen atom and R ' represents an aniline group which may be substituted or a morpholine group, with guanidine in alcoholic solution under conditions of heating under reflux, distilling off the alcohol and heating to boiling the product remaining behind after removal of the alcohol, which product has the general formula VI
in which R has the meaning specified above, in alcoholic hydrochloric acid so that the methoxy methyl group is split off and the product is converted into the desired 2,4-diamino-5-benzylpyrimidine compound and, if desired, con-verting the resulting compound into its pharmacologically acceptable acid addition salt.
in which R represents an alkyl group having from 1 to 4 carbon atoms or a halogen atom, said process being selected from the group consisting of:
(A) by reaction of a 2,4-diamino-5-hydroxymethylpyrimidine of the formula II
with a methoxyphenol of the formula III
wherein R is as defined above, and, if desired, con-verting the compound of formula III into a pharma-cologically acceptable acid addition salt;
(B) formylating a hydrocinnamic acid ester of the general formula IV
wherein R has the meaning specified above and X represents an alkyl group having from 1 to 4 carbon atoms, with ethyl formate in the presence of sodium, condensing the compound obtained with guanidine in an alkaline medium and reacting the resulting 2-amino-4-hydroxy-5-(substituted benzyl)-pyrimidine with phosphorus oxychloride, reacting the chlor-ine compound obtained with ammonia and, if desired, conver-ting the resulting compound into its pharmacologically acceptable acid addition salt; or (C) reacting a .beta.-amino-acrylonitrile of the formula V
in which R represents an alkyl group having from 1 to 4 carbon atoms or a halogen atom and R ' represents an aniline group which may be substituted or a morpholine group, with guanidine in alcoholic solution under conditions of heating under reflux, distilling off the alcohol and heating to boiling the product remaining behind after removal of the alcohol, which product has the general formula VI
in which R has the meaning specified above, in alcoholic hydrochloric acid so that the methoxy methyl group is split off and the product is converted into the desired 2,4-diamino-5-benzylpyrimidine compound and, if desired, con-verting the resulting compound into its pharmacologically acceptable acid addition salt.
2. A process as defined in claim 1 wherein said process is (A).
3. A process as defined in claim 1 wherein said process is (B).
4. A process as defined in claim l wherein said process is (C).
5. A process as defined in claim 2 wherein the reaction is carried out in glacial acetic acid and in the presence of concentrated hydrochloric acid.
6. A process as defined in claim 2 wherein R represents a methyl or ethyl group.
7. A process as defined in claim 3 wherein R represents a methyl or ethyl group.
8. A process as defined in claim 4 wherein R represents a methyl or ethyl group.
9. A process as defined in claim 2 wherein R represents a chlorine or bromine atom.
10. A process as defined in claim 3 wherein R represents a chlorine or bromine atom.
11. A process as defined in claim 4 wherein R represents a chlorine or bromine atom.
12. A 2,4-diamino-5-benzylpyrimidine of the general formula I
in which R represents an alkyl group having from 1 to 4 carbon atoms or a halogen atom, or a pharmacologically acceptable acid addition salt thereof, whenever produced by the process of claim 1, or an obvious chemical equivalent thereof.
in which R represents an alkyl group having from 1 to 4 carbon atoms or a halogen atom, or a pharmacologically acceptable acid addition salt thereof, whenever produced by the process of claim 1, or an obvious chemical equivalent thereof.
13. A 2,4-diamino-5-benzylpyrimidine as defined in claim 12, wherein R represents a methyl or ethyl group, whenever produced by the process of claim 6 or an obvious chemical equivalent thereof.
14. A 2,4-diamino-5-benzylpyrimidine as defined in claim 12, wherein R represents a methyl or ethyl group, whenever produced by the process of claim 7 or an obvious chemical equivalent thereof.
15. A 2,4-diamino-5-benzylpyrimidine as defined in claim 12, wherein R represents a methyl or ethyl group, whenever produced by the process of claim 8 or an obvious chemical equivalent thereof.
16. A 2,4-diamino-5-benzylpyrimidine as defined in claim 12, wherein R represents a chlorine or bromine atom, whenever produced by the process of claim 9 or an obvious chemical equivalent thereof.
17. A 2,4-diamino-5-benzylpyrimidine as defined in claim 12, wherein R represents a chlorine or bromine atom, whenever produced by the process of claim 10 or an obvious chemical equivalent thereof.
18. A 2,4-diamino-5-benzylpyrimidine as defined in claim 12, wherein R represents a chlorine or bromine atom, whenever produced by the process of claim 11 or an obvious chemical equivalent thereof.
19. A 2,4-diamino-5-benzylpyrimidine as defined in claim 12, in the form of its addition salt with hydrochloric acid, hydrobromic acid, sulphuric acid, acetic acid, tartaric acid, fumaric acid, maleic acid or ascorbic acid, whenever produced by the process of claim 2 or an obvious chemical equivalent thereof.
20. A 2,4-diamino-5-benzylpyrimidine as defined in claim .
12, in the form of its addition salt with hydrochloric acid, hydrobromic acid, sulphuric acid, acetic acid, tartaric acid, fumaric acid, maleic acid or ascorbic acid, whenever produced by the process of claim 3 or an obvious chemical equivalent thereof.
12, in the form of its addition salt with hydrochloric acid, hydrobromic acid, sulphuric acid, acetic acid, tartaric acid, fumaric acid, maleic acid or ascorbic acid, whenever produced by the process of claim 3 or an obvious chemical equivalent thereof.
21. A 2,4-diamino-5-benzylpyrimidine as defined in claim 12, in the form of its addition salt with hydrochloric acid, hydrobromic acid, sulphuric acid, acetic acid, tartaric acid, fumaric acid, maleic acid or ascorbic acid, whenever produced by the process of claim 4 or an obvious chemical equivalent thereof.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE2546667A DE2546667C3 (en) | 1975-10-17 | 1975-10-17 | 2,4-DiamuH »-5- (3-methoxy-4-hydroxy-5-halobenzyl) -pyrimidines, and medicinal products containing these compounds |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1055498A true CA1055498A (en) | 1979-05-29 |
Family
ID=5959437
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA262,152A Expired CA1055498A (en) | 1975-10-17 | 1976-09-27 | 2,4-diamino-5-benzylpyrimidines, process for their preparation and pharmaceutical compositions containing these compounds |
Country Status (17)
Country | Link |
---|---|
JP (1) | JPS5251376A (en) |
AR (1) | AR210905A1 (en) |
AT (1) | AT352735B (en) |
AU (1) | AU1724576A (en) |
BE (1) | BE846397A (en) |
CA (1) | CA1055498A (en) |
CH (1) | CH623313A5 (en) |
DE (1) | DE2546667C3 (en) |
ES (1) | ES451375A1 (en) |
FR (1) | FR2327786A1 (en) |
GB (1) | GB1522537A (en) |
GR (1) | GR60352B (en) |
HU (1) | HU174155B (en) |
IL (1) | IL50430A0 (en) |
MX (1) | MX4485E (en) |
NL (1) | NL7609652A (en) |
PT (1) | PT65482B (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2720771C3 (en) | 1977-05-09 | 1979-11-29 | Ludwig Heumann & Co Gmbh, 8500 Nuernberg | 2,4-Diamino-5- (33-dimethoxy-4thioalkyl-benzyD-pyrimidines, process for their preparation and pharmaceuticals containing these compounds |
MA18450A1 (en) * | 1978-05-24 | 1979-12-31 | Wellcome Found | COMPOSITION OF BENZYLPIRIMIDINES |
HU188588B (en) * | 1982-08-13 | 1986-04-28 | Egyt Gyogyszervegyeszeti Gyar | Process for the production of 2,4-diamino-5-benzyl-pyrimidine-derivatives |
-
1975
- 1975-10-17 DE DE2546667A patent/DE2546667C3/en not_active Expired
-
1976
- 1976-07-28 CH CH962676A patent/CH623313A5/en not_active IP Right Cessation
- 1976-08-03 GR GR51404A patent/GR60352B/en unknown
- 1976-08-17 PT PT65482A patent/PT65482B/en unknown
- 1976-08-27 AU AU17245/76A patent/AU1724576A/en not_active Expired
- 1976-08-31 NL NL7609652A patent/NL7609652A/en not_active Application Discontinuation
- 1976-09-01 AT AT649276A patent/AT352735B/en not_active IP Right Cessation
- 1976-09-08 IL IL50430A patent/IL50430A0/en unknown
- 1976-09-09 ES ES451375A patent/ES451375A1/en not_active Expired
- 1976-09-16 FR FR7627872A patent/FR2327786A1/en active Granted
- 1976-09-21 BE BE170783A patent/BE846397A/en unknown
- 1976-09-22 AR AR264813A patent/AR210905A1/en active
- 1976-09-27 CA CA262,152A patent/CA1055498A/en not_active Expired
- 1976-10-01 HU HU76HE722A patent/HU174155B/en unknown
- 1976-10-01 JP JP51118916A patent/JPS5251376A/en active Pending
- 1976-10-01 GB GB40800/76A patent/GB1522537A/en not_active Expired
- 1976-10-01 MX MX764949U patent/MX4485E/en unknown
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Publication number | Publication date |
---|---|
GB1522537A (en) | 1978-08-23 |
GR60352B (en) | 1978-05-18 |
FR2327786A1 (en) | 1977-05-13 |
AT352735B (en) | 1979-10-10 |
DE2546667A1 (en) | 1977-04-28 |
PT65482A (en) | 1976-09-01 |
FR2327786B1 (en) | 1980-04-18 |
PT65482B (en) | 1978-02-13 |
HU174155B (en) | 1979-11-28 |
ES451375A1 (en) | 1981-10-16 |
AU1724576A (en) | 1978-03-02 |
BE846397A (en) | 1977-01-17 |
DE2546667C3 (en) | 1978-10-12 |
DE2546667B2 (en) | 1978-02-09 |
MX4485E (en) | 1982-05-21 |
AR210905A1 (en) | 1977-09-30 |
CH623313A5 (en) | 1981-05-29 |
ATA649276A (en) | 1979-03-15 |
IL50430A0 (en) | 1976-11-30 |
JPS5251376A (en) | 1977-04-25 |
NL7609652A (en) | 1977-04-19 |
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