JP2562872B2 - Method for synthesizing cyano-imidazole compound - Google Patents
Method for synthesizing cyano-imidazole compoundInfo
- Publication number
- JP2562872B2 JP2562872B2 JP61014287A JP1428786A JP2562872B2 JP 2562872 B2 JP2562872 B2 JP 2562872B2 JP 61014287 A JP61014287 A JP 61014287A JP 1428786 A JP1428786 A JP 1428786A JP 2562872 B2 JP2562872 B2 JP 2562872B2
- Authority
- JP
- Japan
- Prior art keywords
- imidazole
- cyano
- imidazole compound
- water
- compound
- 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.)
- Expired - Lifetime
Links
- -1 cyano-imidazole compound Chemical class 0.000 title claims description 16
- 238000000034 method Methods 0.000 title claims description 8
- 230000002194 synthesizing effect Effects 0.000 title claims description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 239000013078 crystal Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 230000007935 neutral effect Effects 0.000 description 8
- 239000000377 silicon dioxide Substances 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- NLJYUXHUESWCOS-UHFFFAOYSA-N N-[(2-methyl-1H-imidazol-5-yl)methylidene]hydroxylamine Chemical compound Cc1ncc(C=NO)[nH]1 NLJYUXHUESWCOS-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- QMQZIXCNLUPEIN-UHFFFAOYSA-N 1h-imidazole-2-carbonitrile Chemical class N#CC1=NC=CN1 QMQZIXCNLUPEIN-UHFFFAOYSA-N 0.000 description 1
- VFMPTSXJYHLYPT-UHFFFAOYSA-N 2,5-dimethyl-1h-imidazole-4-carbonitrile Chemical compound CC1=NC(C#N)=C(C)N1 VFMPTSXJYHLYPT-UHFFFAOYSA-N 0.000 description 1
- SQPCINATQLRGCO-UHFFFAOYSA-N 2-ethyl-1h-imidazole-5-carbonitrile Chemical compound CCC1=NC=C(C#N)N1 SQPCINATQLRGCO-UHFFFAOYSA-N 0.000 description 1
- DVOUNUJDHHZFRS-UHFFFAOYSA-N 2-ethyl-5-methyl-1h-imidazole-4-carbonitrile Chemical compound CCC1=NC(C#N)=C(C)N1 DVOUNUJDHHZFRS-UHFFFAOYSA-N 0.000 description 1
- RRHAYEWIUNALRL-UHFFFAOYSA-N 2-heptadecyl-1H-imidazole-5-carbonitrile Chemical compound CCCCCCCCCCCCCCCCCC1=NC=C(C#N)N1 RRHAYEWIUNALRL-UHFFFAOYSA-N 0.000 description 1
- IZYGCWIXHKMALW-UHFFFAOYSA-N 2-methyl-1h-imidazole-5-carbodithioic acid Chemical compound CC1=NC=C(C(S)=S)N1 IZYGCWIXHKMALW-UHFFFAOYSA-N 0.000 description 1
- GSBGWLFUGNVIFB-UHFFFAOYSA-N 2-methyl-1h-imidazole-5-carbonitrile Chemical compound CC1=NC=C(C#N)N1 GSBGWLFUGNVIFB-UHFFFAOYSA-N 0.000 description 1
- ICBUWBVXFGQXCE-UHFFFAOYSA-N 2-undecyl-1H-imidazole-5-carbonitrile Chemical compound CCCCCCCCCCCC1=NC=C(C#N)N1 ICBUWBVXFGQXCE-UHFFFAOYSA-N 0.000 description 1
- KODWZZOTTOSNLW-UHFFFAOYSA-N 5-methyl-1h-imidazole-4-carbonitrile Chemical compound CC=1NC=NC=1C#N KODWZZOTTOSNLW-UHFFFAOYSA-N 0.000 description 1
- BXRDIGJAQAIRGR-UHFFFAOYSA-N 5-methyl-2-phenyl-1h-imidazole-4-carbonitrile Chemical compound N1C(C#N)=C(C)N=C1C1=CC=CC=C1 BXRDIGJAQAIRGR-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Description
【発明の詳細な説明】 本発明は、シアノ−イミダゾール化合物の合成方法に
関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for synthesizing a cyano-imidazole compound.
産業上の利用分野 本発明の方法によって得られるシアノ−イミダゾール
化合物は、生化学あるいは医薬分野において重要な各種
のイミダゾール化合物の出発原料として使用出来る有用
な化合物である。INDUSTRIAL APPLICABILITY The cyano-imidazole compound obtained by the method of the present invention is a useful compound that can be used as a starting material for various imidazole compounds important in biochemistry or medicine.
発明が解決しようとする課題 生化学あるいは医薬分野において、有用なイミダゾー
ル化合物の出発原料として注目されているシアノ−イミ
ダゾール化合物は、従来の方法では合成の手間のかかる
ものであり、それらの簡単な合成方法の出現が望まれて
来た。DISCLOSURE OF THE INVENTION Problems to be Solved by the Invention In the field of biochemistry or medicine, cyano-imidazole compounds, which have been attracting attention as starting materials for useful imidazole compounds, are complicated to synthesize by conventional methods, and their simple synthesis is required. The advent of methods has been desired.
課題を解決するための手段 本発明者等は、イミダゾール化合物と二硫化炭素を反
応させて得られるイミダゾール−ジチオカルボン酸化合
物（特公昭60−29707号公報参照）が、酢酸ナトリウム
と酢酸の存在下において、塩酸ヒドロキシルアミンの作
用でイミダゾール−アルドキシム化合物を与えることを
知見し、さらに当該イミダゾール−アルドキシム化合物
を無水酢酸で脱水することにより、シアノ−イミダゾー
ル化合物が得られることを見い出し、本発明を完遂する
に至った。Means for Solving the Problems The present inventors have found that an imidazole-dithiocarboxylic acid compound (see JP-B-60-29707) obtained by reacting an imidazole compound with carbon disulfide is present in the presence of sodium acetate and acetic acid. In the present invention, it was found that the action of hydroxylamine hydrochloride gives an imidazole-aldoxime compound, and further by dehydrating the imidazole-aldoxime compound with acetic anhydride, it was found that a cyano-imidazole compound is obtained, and the present invention is completed. Came to.
すなわち、本発明は、 一般式 で示されるイミダゾール−アルドキシム化合物を無水酢
酸と加熱することを特徴とする 一般式 〔但し、式中R2及びR4は前記と同じである〕 で示されるシアノ−イミダゾール化合物の合成方法であ
る。That is, the present invention has the general formula Wherein the imidazole-aldoxime compound represented by the formula is heated with acetic anhydride. [However, in the formula, R 2 and R 4 are the same as the above], which is a method for synthesizing a cyano-imidazole compound.
本発明の実施に当たっては、イミダゾール−アルドキ
シム化合物を適当量の無水酢酸と加熱還流したのち、未
反応の無水酢酸を分解させるため反応系に水を加えて加
熱し、反応混合物を減圧乾固し、乾固物を水に溶かし、
ついで該水溶液をアルカリで中和し、析出結晶を濾取す
る。In carrying out the present invention, after heating the imidazole-aldoxime compound with an appropriate amount of acetic anhydride under reflux, water is added to the reaction system to decompose unreacted acetic anhydride, and the mixture is heated to dryness under reduced pressure. Dissolve the dry matter in water,
Then, the aqueous solution is neutralized with an alkali, and the precipitated crystals are collected by filtration.
このようにして得られた粗目的物であるシアノ−イミ
ダゾール化合物は、必要に応じて常法の再結晶または減
圧蒸留によって精製される。The crude cyano-imidazole compound thus obtained is purified by recrystallization or vacuum distillation according to a conventional method, if necessary.
本発明の方法によって得られる代表的なシアノ−イミ
ダゾール化合物の物性は、次のとおりである。The physical properties of a typical cyano-imidazole compound obtained by the method of the present invention are as follows.
２−メチル−４−シアノイミダゾール 中性無色結晶。m.P.236〜238℃（水）；メタノールに易
溶、熱水および熱アセトンに可溶;TLC（シリカＧ、エタ
ノール、I2発色）:Rf 0.62〜0.68 （カッコ内は透過率％を示す、以下同様） NMR（CD3OD）：δ7.68,S,1H（５位）;2.36,S,3H（メチ
ル） Mass:m/e 107（M+）,80（M+−HCN）,79,66,54,53 ２−エチル−４−シアノイミダゾール 中性無色結晶。m.P.156〜158℃（水）；水およびアルコ
ールに可溶;TLC（シリカＧ、アセトン、I2発色）:Rf 0.
82〜0.85 ２−ウンデシル−４−シアノイミダゾール 中性無色結晶。m.P.123〜126℃（MeOH）;DMSOに易溶、
メタノールおよびアセトンに可溶;TLC（シリカＧ、アセ
トン、I2発色）:Rf 0.81〜0.89 ２−ヘプタデシル−４−シアノイミダゾール 中性無色結晶。m.P.117〜122℃（MeOH）；メタノール、
DMSOおよび酢酸に熱可溶;TLC（シリカＧ、エタノール、
I2発色）:Rf 0.80〜0.88 ４−メチル−５−シアノイミダゾール 中性無色結晶。m.P.144〜146℃（水）；メタノールおよ
びエタノールに易溶、熱水に可溶;TLC（シリカＧ、エタ
ノール、I2発色）:Rf 0.68〜0.73 ２−エチル−４−メチル−５−シアノイミダゾール 中性無色結晶。m.P.154〜156℃（水）；アルコール、ア
セトンおよび熱水に易溶;TLC（シリカＧ、エタノール、
I2発色）:Rf 0.85〜0.90 2,4−ジメチル−５−シアノイミダゾール 中性無色結晶。m.P.164〜165℃（水）；アルコール、ア
セトンおよび熱水に易溶;TLC（シリカＧ、エタノール、
I2発色）:Rf 0.67〜0.72 ２−フェニル−４−メチル−５−シアノイミダゾール 中性無色結晶。m.P.222〜224℃（CH3CN）；メタノール
およびアセトンに可溶;TLC（シリカＧ、アセトン、I2発
色）:Rf 0.84〜0.89 参考例 ２−メチルイミダゾール−４−ジチオカルボン酸0.1
モル（16g），塩酸ヒドロキシルアミン0.1モル（7.0
g），酢酸ナトリウム0.1モル（7.0g），酢酸40mlおよび
水20mlの５者から成る系を45分間加熱還流したのち、塩
酸ヒドロキシルアミン0.05モル（3.5g）と酢酸ナトリウ
ム0.05モル（4.2g）を追加して、さらに30分間加熱還流
を続けた。2-Methyl-4-cyanoimidazole Neutral colorless crystal. mP236-238 ° C (water); easily soluble in methanol, soluble in hot water and hot acetone; TLC (silica G, ethanol, I 2 coloring): Rf 0.62 to 0.68 (Transmittance% in parentheses, the same applies below) NMR (CD 3 OD): δ7.68, S, 1H (5th position); 2.36, S, 3H (methyl) Mass: m / e 107 (M + ). , 80 (M + -HCN), 79,66,54,53 2-Ethyl-4-cyanoimidazole Neutral colorless crystal. mP156-158 ° C (water); soluble in water and alcohol; TLC (silica G, acetone, I 2 color development): Rf 0.
82-0.85 2-Undecyl-4-cyanoimidazole Neutral colorless crystals. mP123-126 ° C (MeOH); easily soluble in DMSO,
Soluble in methanol and acetone; TLC (silica G, acetone, I 2 color development): Rf 0.81 to 0.89 2-Heptadecyl-4-cyanoimidazole Neutral colorless crystal. mP117-122 ° C (MeOH); methanol,
Thermally soluble in DMSO and acetic acid; TLC (silica G, ethanol,
I 2 color): Rf 0.80 to 0.88 4-Methyl-5-cyanoimidazole Neutral colorless crystal. mP144-146 ° C (water); readily soluble in methanol and ethanol, soluble in hot water; TLC (silica G, ethanol, I 2 color development): Rf 0.68-0.73 2-Ethyl-4-methyl-5-cyanoimidazole Neutral colorless crystals. mP154-156 ° C (water); easily soluble in alcohol, acetone and hot water; TLC (silica G, ethanol,
I 2 color): Rf 0.85 to 0.90 2,4-Dimethyl-5-cyanoimidazole Neutral colorless crystal. mP164-165 ° C (water); easily soluble in alcohol, acetone and hot water; TLC (silica G, ethanol,
I 2 color): Rf 0.67 to 0.72 2-Phenyl-4-methyl-5-cyanoimidazole Neutral colorless crystals. mP222~224 ℃ (CH 3 CN); soluble in methanol and acetone; TLC (silica G, acetone, I 2 color): Rf from .84 to .89 Reference example 2-methylimidazole-4-dithiocarboxylic acid 0.1
Mol (16g), hydroxylamine hydrochloride 0.1 mol (7.0
g), 0.1 mol of sodium acetate (7.0 g), 40 ml of acetic acid and 20 ml of water are heated under reflux for 45 minutes, and then 0.05 mol (3.5 g) of hydroxylamine hydrochloride and 0.05 mol (4.2 g) of sodium acetate are added. In addition, heating reflux was continued for another 30 minutes.
ついで反応系を冷却し、析出硫黄を濾別し、濾液を減
圧乾固し、乾固物を再び熱水に溶かして活性炭層に通
し、このようにして得られた濾液のpHを8.0として、再
び減圧乾固し、乾固物をエタノール抽出し、抽出液の減
圧乾固物を少量の熱水に溶かして食塩で該水溶液を飽和
し、冷時析出する結晶を濾取し、さらに水で再結晶して
２−メチルイミダゾール−４−アルドキシム（m.p.88〜
115℃）を0.024モル（3.0g、収率24モル％）を得た。Then the reaction system was cooled, the precipitated sulfur was filtered off, the filtrate was dried under reduced pressure, the dried solid was again dissolved in hot water and passed through an activated carbon layer, and the pH of the thus obtained filtrate was adjusted to 8.0. The mixture was dried under reduced pressure to dryness again, the dried solid was extracted with ethanol, the reduced pressure dried solid of the extract was dissolved in a small amount of hot water, the aqueous solution was saturated with sodium chloride, and crystals precipitated when cold were collected by filtration and further washed with water. Recrystallized to give 2-methylimidazole-4-aldoxime (mp88-
115 ° C.) to give 0.024 mol (3.0 g, yield 24 mol%).
実施例 前記参考例と同様にして合成された２−メチルイミダ
ゾール−４−アルドキシム5.0gと無水酢酸20mlを30分間
加熱還流したのち、反応混合物を30mlの水と混合して数
分間煮沸し、ついでこの溶液を減圧乾固し、乾固物を再
び熱水に溶かして活性炭処理を行ない、濾液のpHを炭酸
ナトリウムで8.0としたのち、減圧濃縮し、析出結晶を
濾取することにより２−メチル−４−シアノイミダゾー
ル（m.P.228〜230℃）を2.7g（収率63モル％）を得た。Example 2-methylimidazole-4-aldoxime (5.0 g) synthesized in the same manner as in the above-mentioned Reference Example and 20 ml of acetic anhydride were heated under reflux for 30 minutes, and then the reaction mixture was mixed with 30 ml of water and boiled for several minutes. This solution was dried under reduced pressure, the dried solid was again dissolved in hot water and treated with activated carbon, the pH of the filtrate was adjusted to 8.0 with sodium carbonate, and then concentrated under reduced pressure, and the precipitated crystals were collected by filtration to give 2-methyl. 2.7 g (yield 63 mol%) of -4-cyanoimidazole (mP228-230 ° C) was obtained.
発明の効果 本発明の方法によれば、生化学あるいは医薬分野にお
いて、出発原料として有用なシアノ−イミダゾール化合
物を容易に合成することができる。EFFECTS OF THE INVENTION According to the method of the present invention, a cyano-imidazole compound useful as a starting material in the field of biochemistry or medicine can be easily synthesized.
───────────────────────────────────────────────────── フロントページの続き 合議体 審判長 柿崎 良男 審判官 宮本 和子 審判官 田中 穣治 (56)参考文献 特開 昭49−127972（ＪＰ，Ａ) 特公 昭41−15168（ＪＰ，Ｂ１) 米国特許4025504（ＵＳ，Ａ) Ｃｈｅｍ．Ａｂ．第70巻第３号 （1969）要約番号11663ｑ Ｃｈｅｍ．Ａｂ．第69巻第９号 （1968）要約番号36034ｃ ─────────────────────────────────────────────────── ─── Continuation of the front page Jury President Yoshio Kakizaki Judge Judge Kazuko Miyamoto Judge Jinji Tanaka (56) References JP49-127972 (JP, A) JP41-15168 (JP, B1) US Patent 4025504 (US, A) Chem. Ab. Volume 70 Number 3 (1969) Abstract No. 11663q Chem. Ab. Volume 69 Number 9 (1968) Abstract No. 36034c
Claims (1)
酸と加熱することを特徴とする 一般式 〔但し、式中R2及びR4は前記と同じである〕 で示されるシアノ−イミダゾール化合物の合成方法。1. A general formula Wherein the imidazole-aldoxime compound represented by the formula is heated with acetic anhydride. [Wherein, R 2 and R 4 are the same as defined above], and a method for synthesizing a cyano-imidazole compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61014287A JP2562872B2 (en) | 1986-01-25 | 1986-01-25 | Method for synthesizing cyano-imidazole compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61014287A JP2562872B2 (en) | 1986-01-25 | 1986-01-25 | Method for synthesizing cyano-imidazole compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62175471A JPS62175471A (en) | 1987-08-01 |
| JP2562872B2 true JP2562872B2 (en) | 1996-12-11 |
Family
ID=11856880
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61014287A Expired - Lifetime JP2562872B2 (en) | 1986-01-25 | 1986-01-25 | Method for synthesizing cyano-imidazole compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2562872B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3811621A1 (en) * | 1988-04-07 | 1989-10-26 | Merck Patent Gmbh | METHOD FOR PRODUCING 1H-IMIDAZOLE-5-CARBONIC ACID ESTERS OR NITRILES AND PYRROL-3,4-CARBONIC ACID ESTERS OR NITRILES AND USE OF THE PRODUCED COMPOUNDS FOR SYNTHESISING PILOCARPINE |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4025504A (en) | 1973-12-14 | 1977-05-24 | Pfizer Inc. | Broad Spectrum antibiotics |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL44350A0 (en) * | 1973-04-05 | 1974-06-30 | Sparamedica Ag | New imidazole derivatives,their manufacture and pharmaceutical compositions containing them |
-
1986
- 1986-01-25 JP JP61014287A patent/JP2562872B2/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4025504A (en) | 1973-12-14 | 1977-05-24 | Pfizer Inc. | Broad Spectrum antibiotics |
Non-Patent Citations (2)
| Title |
|---|
| Ｃｈｅｍ．Ａｂ．第６９巻第９号（１９６８）要約番号３６０３４ｃ |
| Ｃｈｅｍ．Ａｂ．第７０巻第３号（１９６９）要約番号１１６６３ｑ |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS62175471A (en) | 1987-08-01 |
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