US3326905A - 1-(5-nitro-2-furyl)-2-(beta-pyridyl)-ethylene and process for preparation thereof - Google Patents
1-(5-nitro-2-furyl)-2-(beta-pyridyl)-ethylene and process for preparation thereof Download PDFInfo
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- US3326905A US3326905A US430490A US43049065A US3326905A US 3326905 A US3326905 A US 3326905A US 430490 A US430490 A US 430490A US 43049065 A US43049065 A US 43049065A US 3326905 A US3326905 A US 3326905A
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- United States
- Prior art keywords
- furyl
- pyridyl
- nitro
- ethylene
- beta
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Links
- 239000005977 Ethylene Substances 0.000 title claims description 21
- 238000000034 method Methods 0.000 title description 5
- 238000002360 preparation method Methods 0.000 title description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 6
- JGDFBJMWFLXCLJ-UHFFFAOYSA-N copper chromite Chemical compound [Cu]=O.[Cu]=O.O=[Cr]O[Cr]=O JGDFBJMWFLXCLJ-UHFFFAOYSA-N 0.000 claims description 5
- 238000006114 decarboxylation reaction Methods 0.000 claims description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 3
- 150000001447 alkali salts Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- -1 nitrofuran compound Chemical class 0.000 description 5
- 229960001907 nitrofurazone Drugs 0.000 description 4
- 241000222122 Candida albicans Species 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 229940095731 candida albicans Drugs 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- PAEXAIBDCHBNDC-UHFFFAOYSA-N 2-pyridin-4-ylacetic acid Chemical compound OC(=O)CC1=CC=NC=C1 PAEXAIBDCHBNDC-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000223238 Trichophyton Species 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000842 anti-protozoal effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- IAIWVQXQOWNYOU-FPYGCLRLSA-N nitrofural Chemical compound NC(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 IAIWVQXQOWNYOU-FPYGCLRLSA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000699 topical effect Effects 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
- C07D405/06—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 linked by a carbon chain containing only aliphatic carbon atoms
Definitions
- the present invention relates to the new nitrofuran compound 1 (5-nitro-2-furyl)-2-(p-pyridyD-ethylene represented by the formula:
- 1-(5-nitro-2-furyl)-2-(u-(or 'y-)-pyridyl)-ethylene can be prepared by condensing S-nitrofurfural with a-(or -)-methylpyridine and that the compound exhibits antibacterial activity (Belgian Patent No. 613,604 and Belgian Patent No. 615,319).
- Another object of the present invention is to provide a process of making such a new and valuable nitrofuran compound.
- Still another object of the present invention is to pr0- vide pharmaceutical compositions useful in therapy which contain such a new 5-nitrofuran compound as active ingredient.
- the nitrofuran compound according to the present invention completely inhibits the growths of bacteria, fungi and protozoa, such as Escherichia coli, Shigella jlexneri, Staphylococcus aureus, Mycobacterium tuberculosis, Candida albicans, Trichophyton asteroides and T richomonas vaginalis in vitro tests.
- bacteria such as Escherichia coli, Shigella jlexneri, Staphylococcus aureus, Mycobacterium tuberculosis, Candida albicans, Trichophyton asteroides and T richomonas vaginalis in vitro tests.
- the l (5 nitro 2 furyl) 2- (,3 pyridyl) ethyllene has proved to be of considerable value in the prophylaxis or the treatment of systemic infections with microorganisms by oral administration. It may be also used for the treatment of the infections by topical application.
- the 1-(5-nitro-2-furyl)-2-( 3-pyridyl)-ethylene can not be prepared by condensing S-nitrofurfural with st-methyl pyridine, since the fi-methyl group is not reactive.
- the present invention provides a process of making 1 (5 nitro 2 furyl) 2 (,B pyridyl) ethylene which comprises condensing S-nitrofurfural with an alkali salt of (fi-pyridyl) acetic acid in the presence of aceticanhydride to form l-(5-nitro-2-furyl)-2-hydroxycarbonyl- Z-(B-pyridyD-ethylene, followed by the decarboxylation of said 1-(5-nitro-2-furyl)-2-hydroxycarbonyl-2-(pi-pyridyl)-ethylene intermediate in the presence of copper chromite.
- the 1-(5-nitro-2-furyl)-2-(;8-pyridyl)-ethylene can be prepared effectively by decarboxylation with heating of 1- (5 nitro 2 furyl) 2 hydroxycarbonyl 2 (B pyridyl)-ethylene in the presence of copper chromite as a catalyst in a suitable solvent, such as quinoline or aniline.
- Example I To a solution of 10.5 g. of S-nitrofurfural in 149 g. of acetic anhydride was added 13.0 g. of potassium S-pyridyl)-acetate, and the mixture was stirred for 4 hours at room temperature (20-30 C.). Yellow crystals which separate out were dissolved in 10% aqueous potassium carbonate. The solution was acidified with glacial acetic acid and crystals which separate out were filtered, Washed with water and dried to give 15.3 g. of 1-(5-nitro-2-furyl)- 2-hydroxycarbonyl-2-(fi-pyridyD-ethylene, M.P. 240-242" C. (dec.).
- Example 2 A mixture of 25 g. of quinoline and 0.3 g. of copper chromite was heated at 180 C. To the mixture, 30 g. of 1 (5 nitro 2 furyl) 2 hydroxycarbonyl 2 (B pyridyl)-ethylene was added in portions with stirring during 30 minutes. After cooling, the quinoline was evaporated under reduced pressure. The residue was washed with ether and recrystallized from isopropanol to give 1.2 g. of 1-(5-nitro-2-furyl)-2-(fl-pyridyl)-ethylene, M.P. 121 C.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
United States Patent 1-(S-NITRO-2-FURYL)-2-(}3-PYRIDYL)-ETHYLENE AND PROCESS FOR PREPARATION THEREOF Shinsaku Minami, Yamatokoriyama-shi, Akio Fujita,
Ibaragi-shi, Tadatsugu Yamamoto, Osaka, Katsuro Fujimoto, Neyagawa-shi, Osaka-fu, Masanao Shimizu,
Kobe-shi, and Yoshiyuki Takase, Amagasaki-shi, Japan,
assignors to Dainippon Pharmaceutical Co., Ltd., Higashi-ku, Osaka, Japan, a corporation of Japan N0 Drawing. Filed Feb. 4, 1965, Ser. No. 430,490
2 Claims. (Cl. 260-240) The present invention relates to the new nitrofuran compound 1 (5-nitro-2-furyl)-2-(p-pyridyD-ethylene represented by the formula:
It is known that 1-(5-nitro-2-furyl)-2-(u-(or 'y-)-pyridyl)-ethylene can be prepared by condensing S-nitrofurfural with a-(or -)-methylpyridine and that the compound exhibits antibacterial activity (Belgian Patent No. 613,604 and Belgian Patent No. 615,319).
However, these compounds are found to be active in vitro tests, but not in vivo tests.
It is one object of the present invention to produce a nitrofuran compound which has anti-bacterial, fungal and protozoal activities both in vitro and in vivo.
Another object of the present invention is to provide a process of making such a new and valuable nitrofuran compound.
Still another object of the present invention is to pr0- vide pharmaceutical compositions useful in therapy which contain such a new 5-nitrofuran compound as active ingredient.
Other objects of present invention and advantageous features thereof will become apparent as the description proceeds.
The nitrofuran compound according to the present invention completely inhibits the growths of bacteria, fungi and protozoa, such as Escherichia coli, Shigella jlexneri, Staphylococcus aureus, Mycobacterium tuberculosis, Candida albicans, Trichophyton asteroides and T richomonas vaginalis in vitro tests.
Further,'the following tables show that 1-(5-nitro-2- furyl)-2-(B-pyridyl)-ethylene [I] possesses remarkably high in vivo activities against Salmonella typhimurium and Candida albicans infected male mice. The compound was compared with both 1-(5-nitro-2-furyl)-2-(a-pyridyl)-ethylene [II] and 1-(5-nitro-2-furyl)-2-(y-pyridyl)- ethylene [III].
TABLE 1.EFFEC'IS ON THE INFECTION WITH SALMONELLA TYPHIMURIUM Drug Dose 1 (mg/kg.) (1) (II) (III i.p. p.o. i.p. p.o l.p. p.o
tlv y.
2 Survival numbers of mice/total used numbers of mice.
TABLE 2.EFFECTS ON THE INFECTION WITH BOTH CANDIDA ALBI CANS Drug Dose 1 (mg/kg.)
1 Drugs were given by the lntraperltoneal and oral routes five times 0, 5, 10, 24 and 30 hours after intravenous infection, respectively.
2 Survival numbers of mice/total used numbers of mice.
The l (5 nitro 2 furyl) 2- (,3 pyridyl) ethyllene has proved to be of considerable value in the prophylaxis or the treatment of systemic infections with microorganisms by oral administration. It may be also used for the treatment of the infections by topical application.
The 1-(5-nitro-2-furyl)-2-( 3-pyridyl)-ethylene can not be prepared by condensing S-nitrofurfural with st-methyl pyridine, since the fi-methyl group is not reactive.
The present invention provides a process of making 1 (5 nitro 2 furyl) 2 (,B pyridyl) ethylene which comprises condensing S-nitrofurfural with an alkali salt of (fi-pyridyl) acetic acid in the presence of aceticanhydride to form l-(5-nitro-2-furyl)-2-hydroxycarbonyl- Z-(B-pyridyD-ethylene, followed by the decarboxylation of said 1-(5-nitro-2-furyl)-2-hydroxycarbonyl-2-(pi-pyridyl)-ethylene intermediate in the presence of copper chromite.
The condensation between S-nitrofurfural and (p-pyridyl)-acetic acid can be easily effected in the presence of acetic anhydride at room temperature, since the methylene group of (fl-pyridyD-acetic acid is reactive. In this reaction an elevated temperature is unfavorable owing to the decomposition of the product.
The 1-(5-nitro-2-furyl)-2-(;8-pyridyl)-ethylene can be prepared effectively by decarboxylation with heating of 1- (5 nitro 2 furyl) 2 hydroxycarbonyl 2 (B pyridyl)-ethylene in the presence of copper chromite as a catalyst in a suitable solvent, such as quinoline or aniline.
The following examples illustrate an effective process for producing the new compound.
Example I To a solution of 10.5 g. of S-nitrofurfural in 149 g. of acetic anhydride was added 13.0 g. of potassium S-pyridyl)-acetate, and the mixture was stirred for 4 hours at room temperature (20-30 C.). Yellow crystals which separate out were dissolved in 10% aqueous potassium carbonate. The solution was acidified with glacial acetic acid and crystals which separate out were filtered, Washed with water and dried to give 15.3 g. of 1-(5-nitro-2-furyl)- 2-hydroxycarbonyl-2-(fi-pyridyD-ethylene, M.P. 240-242" C. (dec.).
Example 2 A mixture of 25 g. of quinoline and 0.3 g. of copper chromite was heated at 180 C. To the mixture, 30 g. of 1 (5 nitro 2 furyl) 2 hydroxycarbonyl 2 (B pyridyl)-ethylene was added in portions with stirring during 30 minutes. After cooling, the quinoline was evaporated under reduced pressure. The residue was washed with ether and recrystallized from isopropanol to give 1.2 g. of 1-(5-nitro-2-furyl)-2-(fl-pyridyl)-ethylene, M.P. 121 C.
3 What is claimed is: 1. The compound 1-(S-nitro-Z-furyl)-2-(p-pyridyl)- ethylene represented by the formula:
4 decarboxylation of said 1-(5-nitro-2-furyl)-2-hydroxycarbonyl-2-(fl-pyridyl)ethylene intermediate in the presence of copper chromite.
References Cited FOREIGN PATENTS 5/1963 Great Britain.
OTHER REFERENCES Klingsberg: Pyridine and Derivatives, part 2, page 200, Interscience Pub., N.Y. (1961).
JOHN D. RANDOLPH, Primary Examiner.
Claims (2)
1. THE COMPOUND 1-(5-NITRO-2-FURYL)-2(B-PYRIDYL)ETHYLENE REPRESENTED BY THE FORMULA:
2. THE PROCESS FOR PREPARING (-(5-NITRO-2-FURYL)-2(BPYRIDYL)-ETHYLENE WHICH COMPRISES CONDENSING AN ALKALI SALT OF (B-PYRIDYL)-ACETIC ACID WITH 5-NITROFURFURNAL IN THE PRESENCE OF ACETIC ANHYDRODE TO FORM 1-(5-NITRO-2-FURYL)2-HYDROXYCARBONYL-2-NB-PYRIDYL)-ETHYLENE, FOLLOWED BY DECARBOXYLATION OF SAID 1-(5-NITRO-2-FURYL)-2-HYDROXYCARBONYL-2-(B-PYRIDYL)-ETHYLENE INTERMEDIATE IN THE PRESENCE OF COPPER CHROMITE.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US430490A US3326905A (en) | 1965-02-04 | 1965-02-04 | 1-(5-nitro-2-furyl)-2-(beta-pyridyl)-ethylene and process for preparation thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US430490A US3326905A (en) | 1965-02-04 | 1965-02-04 | 1-(5-nitro-2-furyl)-2-(beta-pyridyl)-ethylene and process for preparation thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3326905A true US3326905A (en) | 1967-06-20 |
Family
ID=23707775
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US430490A Expired - Lifetime US3326905A (en) | 1965-02-04 | 1965-02-04 | 1-(5-nitro-2-furyl)-2-(beta-pyridyl)-ethylene and process for preparation thereof |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3326905A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB925569A (en) * | 1961-03-21 | 1963-05-08 | Boehringer & Soehne Gmbh | New 5-nitrofuran derivatives |
-
1965
- 1965-02-04 US US430490A patent/US3326905A/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB925569A (en) * | 1961-03-21 | 1963-05-08 | Boehringer & Soehne Gmbh | New 5-nitrofuran derivatives |
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