CH513916A - Antimicrobial 4-(5-nitro-2-furyl)-pyrimidines - Google Patents
Antimicrobial 4-(5-nitro-2-furyl)-pyrimidinesInfo
- Publication number
- CH513916A CH513916A CH996271A CH996271A CH513916A CH 513916 A CH513916 A CH 513916A CH 996271 A CH996271 A CH 996271A CH 996271 A CH996271 A CH 996271A CH 513916 A CH513916 A CH 513916A
- Authority
- CH
- Switzerland
- Prior art keywords
- furyl
- nitro
- formula
- pyrimidines
- antimicrobial
- Prior art date
Links
- LNUODYKIHBMHOK-UHFFFAOYSA-N [N+](=O)([O-])C1=CC=C(O1)C1=NC=NC=C1 Chemical class [N+](=O)([O-])C1=CC=C(O1)C1=NC=NC=C1 LNUODYKIHBMHOK-UHFFFAOYSA-N 0.000 title abstract description 4
- 230000000845 anti-microbial effect Effects 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 4
- 125000003277 amino group Chemical group 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- FUBFWTUFPGFHOJ-UHFFFAOYSA-N 2-nitrofuran Chemical class [O-][N+](=O)C1=CC=CO1 FUBFWTUFPGFHOJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 2
- 125000004442 acylamino group Chemical group 0.000 claims description 2
- 229940027988 antiseptic and disinfectant nitrofuran derivative Drugs 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- IAIWVQXQOWNYOU-FPYGCLRLSA-N nitrofural Chemical class NC(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 IAIWVQXQOWNYOU-FPYGCLRLSA-N 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 3
- 239000002253 acid Substances 0.000 abstract description 2
- 238000006396 nitration reaction Methods 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 abstract 1
- 230000007062 hydrolysis Effects 0.000 abstract 1
- 238000006460 hydrolysis reaction Methods 0.000 abstract 1
- 208000015181 infectious disease Diseases 0.000 abstract 1
- 210000001635 urinary tract Anatomy 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- -1 6-chloro-2-methyl-4- (5-nitro-2-furyl) -pyrimidine Chemical compound 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- VJXGFDDMTGDMDZ-UHFFFAOYSA-N 2-amino-6-(5-nitrofuran-2-yl)-1h-pyrimidin-4-one Chemical compound NC1=NC(O)=CC(C=2OC(=CC=2)[N+]([O-])=O)=N1 VJXGFDDMTGDMDZ-UHFFFAOYSA-N 0.000 description 1
- BLDDCNKFHYWKAO-UHFFFAOYSA-N 4-chloro-6-(furan-2-yl)-2-methylpyrimidine Chemical compound CC1=NC(Cl)=CC(C=2OC=CC=2)=N1 BLDDCNKFHYWKAO-UHFFFAOYSA-N 0.000 description 1
- LMTYMESROXOBTF-UHFFFAOYSA-N CC=1NC(C=C(N=1)C=1OC(=CC=1)[N+](=O)[O-])=O Chemical compound CC=1NC(C=C(N=1)C=1OC(=CC=1)[N+](=O)[O-])=O LMTYMESROXOBTF-UHFFFAOYSA-N 0.000 description 1
- PMPIEKUWYHNKKK-UHFFFAOYSA-N N-[5-methyl-4-(5-nitrofuran-2-yl)-6-oxo-1H-pyrimidin-2-yl]acetamide Chemical compound C(C)(=O)NC=1NC(C(=C(N1)C=1OC(=CC1)[N+](=O)[O-])C)=O PMPIEKUWYHNKKK-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 150000003951 lactams Chemical group 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000000802 nitrating effect Effects 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Antimicrobial 4-(5-nitro-2-furyl)-pyrimidines... Are novel compounds of the general formula (i), and salts thereof, (where R1 and R2 = H, lower alkyl, alkoxy or opt. acylated amino (same or different) and R3 = H, lower alkoxy, -OH or opt. acylated amino). - They are particularly suitable for the treatment of infections of the urinary tract, and are prepared by the following reactions: nitration right arrow (I) acid right arrow hydrolysis (I) (R3=OH) (where X = Cl or NH2) (where R2 = H or lower alkyl, R4 = alkoxy).
Description
Verfahren zur Herstellung von neuen 5-Nitrofuranderivaten und ihren Salzen Gegenstand der Erfindung ist ein Verfahren zur Herstellung neuer 5-Nitrofuranderivate der Formel I
EMI0001.0002
in der R1 und R2 Wasserstoff, eine niedere Alkyl-, niedere Alkoxy- oder eine gegebenenfalls acylierte Ami- nogruppe bedeuten, und deren physiologisch verträg lichen Salzen.
Diese Substanzen können auch in der tautomeren Lactamform vorliegen; die letztgenannte Form wurde der in den Beispielen gewählten Nomenklatur zugrunde gelegt.
Die Verbindungen der Formel I sind neu und zeich nen sich durch eine gute antimikrobielle Wirkung aus. Insbesondere zur Behandlung von Harnweg-Infektionen sind sie hervorragend geeignet.
Als besonders wirksam haben sich jene 4-(5-Nitro- 2-furyl)-pyrimidinderivate der Formel 1 erwiesen, in de nen R1 eine Methyl-, Amino- oder Acetylaminogruppe, und R2 Wasserstoff oder eine Methylgruppe bedeuten.
Die neuen Verbindungen werden hergestellt, indem man Nitrofuranderivate der Formel II
EMI0001.0009
in der X ein Chloratom oder eine Aminogruppe bedeu tet, der sauren Hydrolyse unterwirft. Hierbei können allfällig in den Ausgangsstoffen der Formel II vorhan dene Acylaminogruppen nachträglich zu Aminogruppen verseift werden.
Die Ausgangsprodukte der Formel II werden durch Nitrierung von Verbindungen der Formel III
EMI0001.0014
erhalten. Die Verbindungen der Formel III können ihrerseits z.
B. auf folgendem Weg erhalten werden:
EMI0002.0000
Als physiologisch unbedenkliche Salze der mit Ami- nogruppen substituierten 4-(5-Nitro-2-furyl)-pyrimidin- Derivate der Formel I kommen insbesondere die Hydro- chloride, Sulfate, Phosphate, Tartrate, Citrate oder Oxa- late in Frage, die z. B. durch Neutralisation mit ent sprechenden Säuren hergestellt werden.
Im nachstehenden Beispiel ist das Verfahren zur Herstellung der neuen Substanzen näher erläutert. <I>Beispiel</I> 0,48 g 6-Chlor-2-methyl-4-(5-nitro-2-furyl)-pyrimi- din werden mit 0,34 g wasserfreiem Natriumacetat in 5 ml Eisessig drei Stunden unter Rückfluss gekocht. Nach dem Abkühlen wird mit Sodalösung neutralisiert, abgesaugt, mit Wasser gewaschen und aus Dimethyl- formamid umkristallisiert. Ausbeute: 0,2 g (45 %) 2- Methyl-4-(5-nitro-2-furyl)-6(1H)-pyrimidinon. Dieses Produkt schmilzt bei 305 C.
Das als Ausgangsmaterial verwendete 6-Chlor-2- methyl-4-(5-nitro-2-furyl)-pyrimidin, Fp. 173 bis 176 C, wird durch Nitrieren von 6-Chlor-4-(2-furyl)-2-me- thyl-pyrimidin erhalten.
In analoger Weise erhält man die folgenden Sub stanzen: 2-Acetamido-5-methyl-4-(5-nitro-2-furyl)-6(1H)-py- rimidinon, Ausbeute 82% der Theorie, Fp. 305 bis 307 C (Dimethylformamid); 2-Amino-5-methyl-4-(5-nitro-2- furyl)-6(1H)-pyrimidinon. Ausbeute 98 % der Theorie, Fp. 350 C.
2-Acetamido-4-(5-nitro-2-furyl)-6(1H)-pyrimidi- non, Ausbeute 91% der Theorie, Fp. 297 bis 303 C (Zers.); 2-Amino-4-(5-nitro-2-furyl)-6(1H)-pyrimidinon, Ausbeute 84,5 % der Theorie, Fp. 330 bis 337 C (Zers.); 2,5-Dimethyl-4-(5-nitro-2-furyl)-6(11)-pyrimidinon, Ausbeute 42,5 % der Theorie, Fp. 315 C (Dimethyl- formamid).
Process for the preparation of new 5-nitrofuran derivatives and their salts The invention relates to a process for the preparation of new 5-nitrofuran derivatives of the formula I.
EMI0001.0002
in which R1 and R2 denote hydrogen, a lower alkyl, lower alkoxy or an optionally acylated amino group, and their physiologically compatible salts.
These substances can also be in the tautomeric lactam form; the nomenclature chosen in the examples was based on the latter form.
The compounds of formula I are new and are characterized by a good antimicrobial effect. They are particularly suitable for treating urinary tract infections.
Those 4- (5-nitro-2-furyl) -pyrimidine derivatives of the formula 1 in which R1 is a methyl, amino or acetylamino group and R2 is hydrogen or a methyl group have proven particularly effective.
The new compounds are prepared by adding nitrofuran derivatives of the formula II
EMI0001.0009
in which X denotes a chlorine atom or an amino group which is subjected to acid hydrolysis. In this case, any acylamino groups in the starting materials of the formula II can be saponified subsequently to give amino groups.
The starting products of the formula II are by nitration of compounds of the formula III
EMI0001.0014
receive. The compounds of formula III can in turn, for.
B. obtained in the following way:
EMI0002.0000
Physiologically acceptable salts of the 4- (5-nitro-2-furyl) -pyrimidine derivatives of the formula I substituted with amino groups are, in particular, the hydrochlorides, sulfates, phosphates, tartrates, citrates or oxalates, which z. B. be prepared by neutralization with ent speaking acids.
The following example explains the process for producing the new substances in more detail. <I> Example </I> 0.48 g of 6-chloro-2-methyl-4- (5-nitro-2-furyl) -pyrimidine are mixed with 0.34 g of anhydrous sodium acetate in 5 ml of glacial acetic acid for three hours Boiled under reflux. After cooling, it is neutralized with soda solution, filtered off with suction, washed with water and recrystallized from dimethylformamide. Yield: 0.2 g (45%) 2-methyl-4- (5-nitro-2-furyl) -6 (1H) -pyrimidinone. This product melts at 305 C.
The 6-chloro-2-methyl-4- (5-nitro-2-furyl) -pyrimidine used as starting material, melting point 173 to 176 ° C., is obtained by nitrating 6-chloro-4- (2-furyl) -2 -methyl-pyrimidine obtained.
The following substances are obtained in an analogous manner: 2-Acetamido-5-methyl-4- (5-nitro-2-furyl) -6 (1H) -pyrimidinone, yield 82% of theory, melting point 305-307 C (dimethylformamide); 2-Amino-5-methyl-4- (5-nitro-2-furyl) -6 (1H) -pyrimidinone. Yield 98% of theory, m.p. 350 C.
2-Acetamido-4- (5-nitro-2-furyl) -6 (1H) -pyrimidinone, yield 91% of theory, melting point 297 to 303 C (dec.); 2-Amino-4- (5-nitro-2-furyl) -6 (1H) -pyrimidinone, yield 84.5% of theory, melting point 330 to 337 C (dec.); 2,5-Dimethyl-4- (5-nitro-2-furyl) -6 (11) -pyrimidinone, yield 42.5% of theory, melting point 315 C (dimethylformamide).
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19681770831 DE1770831A1 (en) | 1968-07-09 | 1968-07-09 | 5-nitrofuran derivatives and process for making the same |
| CH1034169A CH513915A (en) | 1968-07-09 | 1969-07-07 | Process for the production of new 5-nitrofuran derivatives and their salts |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH513916A true CH513916A (en) | 1971-10-15 |
Family
ID=25706371
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH996271A CH513916A (en) | 1968-07-09 | 1969-07-07 | Antimicrobial 4-(5-nitro-2-furyl)-pyrimidines |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH513916A (en) |
-
1969
- 1969-07-07 CH CH996271A patent/CH513916A/en not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |