JPH0121153B2 - - Google Patents
Info
- Publication number
- JPH0121153B2 JPH0121153B2 JP54068570A JP6857079A JPH0121153B2 JP H0121153 B2 JPH0121153 B2 JP H0121153B2 JP 54068570 A JP54068570 A JP 54068570A JP 6857079 A JP6857079 A JP 6857079A JP H0121153 B2 JPH0121153 B2 JP H0121153B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- methyl
- tetrazol
- acetamide
- thiomethyl
- 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
Links
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 19
- -1 1-dimethylaminoethyl-1H-tetrazole Chemical compound 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 7
- 230000000844 anti-bacterial effect Effects 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000002329 infrared spectrum Methods 0.000 description 7
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 7
- 150000003536 tetrazoles Chemical class 0.000 description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
- 238000000921 elemental analysis Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 4
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229920001429 chelating resin Polymers 0.000 description 3
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- GCXSLHXGZHFXRG-UHFFFAOYSA-N 2-(diaminomethylideneamino)acetyl chloride;hydrochloride Chemical compound Cl.NC(=N)NCC(Cl)=O GCXSLHXGZHFXRG-UHFFFAOYSA-N 0.000 description 2
- QHJJSLUZWHFHTK-UHFFFAOYSA-N 3-amino-3-azaniumylidenepropanoate Chemical compound NC(=N)CC(O)=O QHJJSLUZWHFHTK-UHFFFAOYSA-N 0.000 description 2
- 229930186147 Cephalosporin Natural products 0.000 description 2
- 229940126062 Compound A Drugs 0.000 description 2
- 108010016626 Dipeptides Proteins 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 229940124587 cephalosporin Drugs 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical group NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- OMAFFHIGWTVZOH-UHFFFAOYSA-N 1-methyltetrazole Chemical compound CN1C=NN=N1 OMAFFHIGWTVZOH-UHFFFAOYSA-N 0.000 description 1
- DJZUHCWDJZDEML-UHFFFAOYSA-N 2-[(n'-methylcarbamimidoyl)amino]acetyl chloride;hydrochloride Chemical compound Cl.CNC(=N)NCC(Cl)=O DJZUHCWDJZDEML-UHFFFAOYSA-N 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 241000588697 Enterobacter cloacae Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 241000588767 Proteus vulgaris Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 description 1
- 229960001139 cefazolin Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 229940007042 proteus vulgaris Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical group O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000006227 trimethylsilylation reaction Methods 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
Landscapes
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、新規なセフアロスポリン誘導体に関
するものである。
従来よりセフエム誘導体は抗菌剤として種々の
ものが開発されており、セフエム骨格の７位アミ
ノ基にジペプチドを結合させた誘導体が強い抗菌
活性を示すことが見出されたが、本発明者はこの
ジペプチドの末端アミノ酸のアミノ基をアミジノ
基、グアニジノ基、環状グアニジノ基などに変換
させることにより、より強い抗菌活性を有する化
合物が得られることを見出し、本発明を完成し
た。本発明の化合物は次の一般式（）で表わさ
れる。
式中、R1およびR2はＨもしくはメチル、エチ
ル、プロピル等の低級アルキル基を示すか、R1
およびR2で非置換アルキレン基を示し、R3およ
びR4はＨを示す。ｎは１を示し、ｍは０または
１を示す。Ｚはメチレン、エチレン、プロピレン
等の非置換アルキレン基を示す。R5は低級アル
キルもしくは置換アミノ低級アルキル基が置換す
ることもある異種原子含有五員環例えば１−メチ
ル−1H−テトラゾール、１−ジメチルアミノエ
チル−1H−テトラゾールの如きテトラゾールま
たはトリアゾールなどがある。ｍがＯを示すとき
は、（ ）内の部分が存在せずその前後が直接結
合することを意味する。
本発明の化合物（）を製するには種々の方法
が考えられるが、例えば式
で表わされる7β−〔２−アミノ−２−（２−アミ
ノチアゾール−４−イル）アセトアミド〕−３−
複素環チオメチル−３−セフエム−４−カルボン
酸にアミジノ基、グアニジノ基又は環状グアニジ
ノ基等で置換された酢酸又はプロピオン酸等の酸
クロリドを脱酸剤の存在下に反応させればよい。
一例を述べればアミジノ酢酸の塩酸塩をジクロ
ロメタン中、五塩化燐で酸クロリドとし単離す
る。化合物（）をアセトニトリル中室温にて
Ｎ，Ｏ−ビス（トリメチルシリル）アセトアミド
を加えてトリメチルシリル化した後、脱酸剤とし
てプロピレンオキサイド又はトリエチルアミンの
如き塩基を加え冷却する。本反応液に−5゜〜10
℃、好ましくは0゜〜５℃にて最初に得たアミジノ
酢酸の酸クロリド塩酸塩を数回に分けて加え１〜
２時間撹拌する。次いで反応液を室温にて更に
0.5〜１時間反応させる。反応後含水溶媒例えば
水−テトラヒドロフランを加えてトリメチルシリ
ル基を脱離せしめた後溶媒を溜去する。濃縮残渣
にアルコールの如き溶媒を加えて粗結晶を析出せ
しめた後単するか又は濃縮残渣をそのまま適当な
樹脂、例えばアンバーライトXADを用いるカ
ラムクロマトグラフイーで分離精製すれば目的化
合物を得ることができる。
かくして製される本発明のセフアロスポリン誘
導体は２−アミノチアゾール基が結合する炭素原
子およびＺの種類によつてはその炭素原子が不斉
炭素原子となることがあるから数種類の光学活性
体が生じうる。これ等光学活性体は、適当な光学
活性の原料を用いて製造する方法で得るのが便利
であり、効果の面から一般的にＤ体を使用するこ
とが好ましい。また２−アミノチアゾール−４−
イル−グリシンはラセミ体を使用しても良いが、
効果の面から光学活性体、特にＤ体が好ましい。
本発明化合物は広い抗菌スペクトルを有し、高
い抗菌活性を示すが、特に従来のセフエム系化合
物に耐性を示すプロテウス・ブルガリス、エンテ
ロバクター・クロアカエ、エンテロバクター・エ
ロゲネス、セラチア、マルセツセンスに強い抗菌
活性を呈し、またシユードモナス・エナギノーザ
を除き常用β−ラクタム抗生物質に高度の耐性を
示すブドウ糖非醗酵性グラム陰性桿菌及びストレ
プトコツカス、フエカーリスにも抗菌活性を示す
特徴を有している。
本発明化合物の数列についての抗菌力を公知の
代表的セフエム系化合物セフアゾリンと比較して
最小発育阻止濃度（MIC μｇ／ml：菌量106／
ml）で次表に示す。
The present invention relates to novel cephalosporin derivatives. Various Cefem derivatives have been developed as antibacterial agents, and it was discovered that a derivative with a dipeptide bonded to the 7-position amino group of the Cefem skeleton exhibits strong antibacterial activity. The present invention was completed based on the discovery that a compound with stronger antibacterial activity can be obtained by converting the amino group of the terminal amino acid of a dipeptide into an amidino group, guanidino group, cyclic guanidino group, etc. The compound of the present invention is represented by the following general formula (). In the formula, R 1 and R 2 represent H or a lower alkyl group such as methyl, ethyl, propyl, or R 1
and R 2 represents an unsubstituted alkylene group, and R 3 and R 4 represent H. n represents 1, and m represents 0 or 1. Z represents an unsubstituted alkylene group such as methylene, ethylene or propylene. R 5 is a heteroatom-containing five-membered ring which may be substituted with lower alkyl or substituted amino lower alkyl groups, such as tetrazole or triazole such as 1-methyl-1H-tetrazole and 1-dimethylaminoethyl-1H-tetrazole. When m represents O, it means that the part in parentheses does not exist and the parts before and after it are directly combined. Various methods can be considered for producing the compound () of the present invention, for example, the formula 7β-[2-amino-2-(2-aminothiazol-4-yl)acetamide]-3-
Heterocyclic thiomethyl-3-cephem-4-carboxylic acid may be reacted with an acid chloride such as acetic acid or propionic acid substituted with an amidino group, a guanidino group, a cyclic guanidino group, etc. in the presence of a deoxidizing agent. In one example, the hydrochloride of amidinoacetic acid is isolated as the acid chloride with phosphorus pentachloride in dichloromethane. After the compound () is trimethylsilylated in acetonitrile at room temperature by adding N,O-bis(trimethylsilyl)acetamide, a base such as propylene oxide or triethylamine is added as a deoxidizing agent and the mixture is cooled. −5° to 10° to this reaction solution
℃, preferably 0° to 5°C, add the initially obtained acid chloride hydrochloride of amidinoacetic acid in several portions.
Stir for 2 hours. The reaction solution was then further heated at room temperature.
Allow to react for 0.5-1 hour. After the reaction, a water-containing solvent such as water-tetrahydrofuran is added to remove the trimethylsilyl group, and then the solvent is distilled off. The target compound can be obtained by adding a solvent such as alcohol to the concentrated residue to precipitate crude crystals, or by separating and purifying the concentrated residue as it is by column chromatography using a suitable resin, such as Amberlite XAD. can. Depending on the carbon atom to which the 2-aminothiazole group is bonded and the type of Z, the cephalosporin derivative of the present invention produced in this manner may be an asymmetric carbon atom, and thus several types of optically active forms may be produced. . It is convenient to obtain these optically active forms by a manufacturing method using suitable optically active raw materials, and it is generally preferable to use the D form from the viewpoint of effectiveness. Also, 2-aminothiazole-4-
Racemic form of yl-glycine may be used, but
From the viewpoint of effectiveness, optically active forms, particularly D forms, are preferred. The compound of the present invention has a broad antibacterial spectrum and exhibits high antibacterial activity, but has particularly strong antibacterial activity against Proteus vulgaris, Enterobacter cloacae, Enterobacter erogenes, Serratia, and Marcetuscens, which are resistant to conventional cephem compounds. It also exhibits antibacterial activity against non-glucose-fermenting Gram-negative bacilli, Streptococcus and Fuecalis, which are highly resistant to commonly used β-lactam antibiotics, with the exception of Pseudomonas enaginosa. The antibacterial activity of a series of compounds of the present invention was compared with that of a known representative cefem compound, cefazolin, and the minimum inhibitory concentration (MIC μg/ml: bacterial mass 10 6 /
ml) as shown in the table below.
【表】
化合物Ａ：
7β−〔DL−２−〔DL−２−アミノジノプロピ
オンアミド）−２−（２−アミノチアゾール−４
−イル）アセトアミド〕−３−（１−メチル−
1H−テトラゾール−５−イル）チオメチル−
３−セフエム−４−カルボン酸（R1＝R2＝R3
＝Ｈ、ｍ＝Ｏ、Ｚ＝CH（CH3）、ｎ＝１、R5＝
１−メチル−1H−テトラゾール−５−イル）
化合物Ｂ：
7β−〔DL−２−（２−アミジノアセトアミド）
−２−（２−アミノチアゾール−４−イル）ア
セトアミド〕−３−（１−メチル−1H−テトラ
ゾール−５−イル）チオメチル−３−セフエム
−４−カルボン酸（R1＝R2＝R3＝Ｈ、ｍ＝０、
Ｚ＝CH2、ｎ＝１、R5＝１−メチル−1H−テ
トラゾール−５−イル
化合物Ｃ：
7β−〔DL−２−（２−グアニジノアセトアミ
ド）−２−（２−アミノチアゾール−４−イル）
アセトアミド〕−３−（１−メチル−1H−テト
ラゾール−５−イル）チオメチル−３−セフエ
ム−４−カルボン酸（R1＝R2＝R3＝R4＝Ｈ、
ｍ＝１、Ｚ＝CH2、ｎ＝１、R5＝１−メチル
−1H−テトラゾール−５−イル）
化合物Ｄ：
7β−｛DL−２−〔２−（３−メチルグアニジ
ノ）アセトアミド〕−２−（２−アミノチアゾー
ル−４−イル）アセトアミド｝−３−（１−メチ
ル−1H−テトラゾール−５−イル）チオメチ
ル−３−セフエム−４−カルボン酸（（R1＝R3
＝R4＝Ｈ、R2＝CH3、ｍ＝１、Ｚ＝CH2、ｎ
＝１、R5＝１−メチル−1H−テトラゾール５
−イル）
化合物Ｅ：
7β−｛DL−２−〔２−（イミダゾリン−２−イ
ル−アミノ）アセトアミド〕−２−（２−アミノ
チアゾール−４−イル）アセトアミド｝−３−
（１−メチル−1H−テトラゾール−５−イル）
チオメチル−３−セフエム−４−カルボン酸
（R1＋R2＝−CH2CH2−、R3＝R4＝Ｈ、ｍ＝
１、Ｚ＝CH2、ｎ＝１、R5＝１−メチル−1H
−テトラゾール−５−イル）
化合物Ｆ：
7β−〔DL−２−（３−グアニジノプロピオン
アミド）−２−（２−アミノチアゾール−４−イ
ル）アセトアミド〕−３−（１−メチル−1H−
テトラゾール−５−イル）チオメチル−３−セ
フエム−４−カルボン酸（R1＝R2＝R3＝R4＝
Ｈ、ｍ＝１、Ｚ＝CH2CH2、ｎ＝１、R5＝１
−メチル−1H−テトラゾール−５−イル）
化合物Ｇ：
7β−〔DL−２−（２−グアニジノアセトアミ
ド）−２−（２−アミノチアゾール−４−イル）
アセトアミド〕−３−〔１−（２−ジメチルアミ
ノエチル）−1H−テトラゾール−５−イル〕チ
オメチル−３−セフエム−４−カルボン酸
（R1＝R2＝R3＝R4＝Ｈ、ｍ＝11、Ｚ＝CH2、ｎ
＝１、R5＝１−（２＝ジメチルアミノエチル）
−1H−テトラゾール−５−イル）
実施例 １
化合物Ａの製造
7β−〔DL−２−アミノ−２−（２−アミノチア
ゾール−４−イル）アセトアミド〕−３−（１−メ
チル−1H−テトラゾール−５−イル）チオメチ
ル−３−セフエム−４−カルボン酸387mgを無水
アセトニトリル４mlに懸濁し、ついでこれにＮ，
Ｏ−ビス（トリメチルシリル）アセトアミドの２
モルクロロホルム溶液２mlを加えてトリメチルシ
リル化した後プロピレンオキサイド0.15mlを加え
る。これにDL−２−アミジノプロピオン酸クリ
ロド塩酸塩151mgを氷冷下撹拌しつゝ加え、同温
度で３時間撹拌する。反応液に水５ml、テトラヒ
ドロフラン５mlの混液を加え減圧下に有機溶媒を
留去する。残つた水層部を酢酸エチルで抽出した
後水層部をアンバーライトXADのカラムに通
して精製し7β−〔DL−２−（DL−２−アミジノプ
ロピオンアミド）−２−（２−アミノチアゾール−
４−イル）アセトアミド〕−３−（１−メチル−
1H−テトラゾール−５−イル）チオメチル−３
−セフエム−４−カルボン酸を得た。210mg。
元素分析値C19H23N11O5S3・1.5H2O
計算値 C37.49、H4.31、N25.31
実測値 C37.81、H4.11、N25.17
NMRスペクトル（90MHz、D2O＋Py−d5の混液
中）δppm
1.71、1.78（3H、each ｓ、DL体による
[Table] Compound A: 7β-[DL-2-[DL-2-aminodinopropionamide)-2-(2-aminothiazole-4
-yl)acetamide]-3-(1-methyl-
1H-tetrazol-5-yl)thiomethyl-
3-cephem-4-carboxylic acid (R 1 = R 2 = R 3
=H, m=O, Z=CH( CH3 ), n=1, R5 =
1-Methyl-1H-tetrazol-5-yl) Compound B: 7β-[DL-2-(2-amidinoacetamide)
-2-(2-aminothiazol-4-yl)acetamide]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (R 1 = R 2 = R 3 =H, m=0,
Z= CH2 , n=1, R5 =1-methyl-1H-tetrazol-5-yl Compound C: 7β-[DL-2-(2-guanidinoacetamide)-2-(2-aminothiazol-4- )
acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (R 1 = R 2 = R 3 = R 4 = H,
m=1, Z= CH2 , n=1, R5 =1-methyl-1H-tetrazol-5-yl) Compound D: 7β-{DL-2-[2-(3-methylguanidino)acetamide]- 2-(2-aminothiazol-4-yl)acetamido}-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid ((R 1 = R 3
=R 4 =H, R 2 =CH 3 , m=1, Z=CH 2 , n
= 1, R 5 = 1-methyl-1H-tetrazole 5
-yl) Compound E: 7β-{DL-2-[2-(imidazolin-2-yl-amino)acetamide]-2-(2-aminothiazol-4-yl)acetamide}-3-
(1-methyl-1H-tetrazol-5-yl)
Thiomethyl-3-cephem-4-carboxylic acid (R 1 + R 2 = -CH 2 CH 2 -, R 3 = R 4 = H, m =
1, Z= CH2 , n=1, R5 =1-methyl-1H
-tetrazol-5-yl) Compound F: 7β-[DL-2-(3-guanidinopropionamide)-2-(2-aminothiazol-4-yl)acetamide]-3-(1-methyl-1H-
Tetrazol-5-yl) thiomethyl-3-cephem-4-carboxylic acid (R 1 = R 2 = R 3 = R 4 =
H, m=1, Z=CH 2 CH 2 , n=1, R 5 =1
-Methyl-1H-tetrazol-5-yl) Compound G: 7β-[DL-2-(2-guanidinoacetamide)-2-(2-aminothiazol-4-yl)
acetamido]-3-[1-(2-dimethylaminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (R 1 = R 2 = R 3 = R 4 = H, m =11, Z=CH 2 , n
=1, R 5 =1-(2=dimethylaminoethyl)
-1H-tetrazol-5-yl) Example 1 Production of compound A 7β-[DL-2-amino-2-(2-aminothiazol-4-yl)acetamide]-3-(1-methyl-1H-tetrazole 387 mg of -5-yl)thiomethyl-3-cephem-4-carboxylic acid was suspended in 4 ml of anhydrous acetonitrile, and then N,
O-bis(trimethylsilyl)acetamide 2
Add 2 ml of molar chloroform solution to perform trimethylsilylation, and then add 0.15 ml of propylene oxide. To this was added 151 mg of DL-2-amidinopropionic acid chloride hydrochloride with stirring under ice cooling, and the mixture was stirred at the same temperature for 3 hours. A mixture of 5 ml of water and 5 ml of tetrahydrofuran was added to the reaction solution, and the organic solvent was distilled off under reduced pressure. After extracting the remaining aqueous layer with ethyl acetate, the aqueous layer was purified by passing it through an Amberlite XAD column to obtain 7β-[DL-2-(DL-2-amidinopropionamide)-2-(2-aminothiazole). −
4-yl)acetamido]-3-(1-methyl-
1H-tetrazol-5-yl)thiomethyl-3
-Cefem-4-carboxylic acid was obtained. 210mg. Elemental analysis value C 19 H 23 N 11 O 5 S 3・1.5H 2 O Calculated value C37.49, H4.31, N25.31 Actual value C37.81, H4.11, N25.17 NMR spectrum (90MHz, D 2 O + Py-d in a mixture of 5 ) δppm 1.71, 1.78 (3H, each s, DL body)
【式】）
3.2〜4.0（2H、bro、２−Ｈ）
4.07、4.09（3H、each ｓ、DL体によるテトラゾ
ール１−CH3）
4.35（2H、bro ｓ、３−CH2）
5.72（1H、ｓ、チアゾリルグリシンCH）
5.81、5.93（1H、each ｄ、Ｊ＝５Hz、DL体によ
る７−Ｈ）
6.87、6.90（1H、each ｓ、DL体によるチアゾー
ル５−Ｈ）
IRスペクトルνKBr nax1765、1680、1600、1510cm-1
実施例 ２
化合物Ｂの製造
7β−〔DL−２−アミノ−２−（２−アミノチア
ゾール−４−イル）アセトアミド〕−３−（１−メ
チル−1H−テトラゾール−５−イル）チオメチ
ル−３−セフエム−４−カルボン酸387mgを無水
アセトニトリル６mlに懸濁し、ついでこれにＮ，
Ｏ−ビス（トリメチルシリル）アセトアミドの２
モルクロロホルム溶液２mlを加えてトリメチルシ
リル化した後プロピレンオキサイド0.36mlを加え
る。反応液を氷冷下撹拌しつゝ２−アミジノ酢酸
クロリド塩酸塩190mgを加え20分間撹拌する。更
に２−アミジノ酢酸クロリド塩酸塩190mgを加え
て氷冷下に20分間撹拌した後プロピレンオキサイ
ド0.4ml及び２−アミジノ酢酸クロリド塩酸塩190
mgを加える。反応液を20分間撹拌した後再度２−
アミジノ酢酸クロリド塩酸塩140mgを加えて20分
間撹拌する。ついで反応液を室温に戻し１時間撹
拌する。反応液に水３ml、テトラヒドロフラン７
mlの混液を加え減圧下に有機溶媒を留去し残つた
水層部をアンバーライトXADのカラムに通し
て精製し7β−〔DL−２−（２−アミジノアセトア
ミド）−２−（２−アミノチアゾール−４−イル）
アセトアミド〕−３−（１−メチル−1H−テトラ
ゾール−５−イル）チオメチル−３−セフエム−
４−カルボン酸を得た。155mg。
元素分析値C18H21N11O5S3・H2O
計算値 C36.92、H3.96、N26.31
実測値 C36.59、H3.82、N26.01
NMRスペクトル（90MHz、D2O＋Py−d5の混液
中）δppm
3.3〜4.0（2H、bro、２−Ｈ）
4.06、4.08（3H、each ｓ、DL体によるテトラゾ
ール１−CH3）
4.35（2H、bro ｓ、３−CH2）
5.73（1H、ｓ、チアゾリルグリシンCH）
5.83、5.93（1H、each ｄ、Ｊ＝５Hz、DL体によ
る７−Ｈ）
6.85、6.88（1H、each、ｓ、DL体によるチアゾ
ール５−Ｈ）
IRスペクトルνKBr nax1760、1690、1610、1520cm-1
実施例 ３
化合物Ｃの製造
7β−〔DL−２−アミノ−２−（２−アミノチア
ゾール−４−イル）アセトアミド〕−３−（１−メ
チル−1H−テトラゾール−５−イル）チオメチ
ル−３−セフエム−４−カルボン酸387mgとグア
ニジノ酢酸クロリド塩酸塩300mgを実施例２と同
様に反応させ化合物C200mgを得た。
元素分析C18H22N12O5S3・H2O
計算値 C35.99、H4.03、N27.98
実測値 C35.70、H3.87、N27.67
NMRスペクトル（90MHz、D2O＋Py−d5の混液
中）δppm
3.3〜4.2（2H、bro、２−Ｈ）
4.07、4.09（3H、each ｓ、DL体によるテトラゾ
ール１−CH3）
4.33（4H、bro ｓ、３−CH2及びグアニジノア
セチル−CH2）
5.75（1H、ｓ、チアゾリールグリシン−CH
5.84、5.94（1H、each ｄ、Ｊ＝4.5Hz、DL体に
よる７−Ｈ）
6.87、6.90（1H、each ｓ、DL体によるチアゾー
ル５−Ｈ）
IRスペクトルνKBr nax1765、1670、1520cm-1
実施例 ４
化合物Ｄの製造
7β−〔DL−２−アミノ−２−（２−アミノチア
ゾール−４−イル）アセトアミド〕−３−（１−メ
チル−1H−テトラゾール−５−イル）チオメチ
ル−３−セフエム−４−カルボン酸387mgと２−
（３−メチルグアニジノ）酢酸クロリド塩酸塩460
mgを実施例２と同様に反応させ化合物D245mgを
得た。
元素分析値C19H24N12O5S3・H2O
計算値 C37.13、H4.26、N27.34
実測値 C37.42、H4.49、N27.08
NMRスペクトル（90MHz、D2O＋Py−d5の混液
中）δppm
2.97（3H、ｓ、グアニジン３−CH3）
3.2〜4.1（2H、bro、２−Ｈ）
4.04、4.06（3H、each ｓ、DL体によるテトラゾ
ール１−CH3）
4.25（4H、bro ｓ、３−CH2及びグアニジノア
セチル CH2）
5.19、5.28（1H、each ｄ、Ｊ＝4.5Hz、DL体に
よる６−Ｈ）
5.66（1H、ｓ、チアゾリールグリシンCH）
5.74、5.84（1H、each ｄ、Ｊ＝4.5Hz、DL体に
よる７−Ｈ）
6.80、6.82（1H、each ｓ、DL体によるチアゾー
ル５−Ｈ）
IRスペクトルνKBr nax1760、1665、1515cm-1
実施例 ５
化合物Ｅの製造
7β−〔DL−２−アミノ−２−（２−アミノチア
ゾール−４−イル）アセトアミド〕−３−（１−メ
チル−1H−テトラゾール−５−イル）チオメチ
ル−３−セフエム−４−カルボン酸387mgと２−
（イミダゾリン−２−イル−アミノ）酢酸クロリ
ド塩酸塩400mgを実施例２と同様に反応させ化合
物E150mgを得た。
元素分析値C20H24N12O5N3・H2O
計算値 C38.33、H4.18、N26.82
実測値 C38.21、H4.02、N26.34
NMRスペクトル（D2O＋Py−d5の混液中）
δppm
3.79（4H、ｓ、イミダゾリン−CH2−CH2−）
4.03（3H、ｓ、テトラゾール１−CH3）
4.02（4H、bro、３−CH2及び（イミダゾリン−
２−イル−アミノ）アセチルCH2）
5.23（1H、６−Ｈ）
5.60（1H、ｓ、チアゾリルグリシンCH）
5.83（1H、７−Ｈ）
6.80（1H、チアゾール５−Ｈ）
IRスペクトルνKBr nax1765、1675、1600、1515cm-1
実施例 ６
化合Ｆの製造
7β−〔DL−２−アミノ−２−（２−アミノチア
ゾール−４−イル）アセトアミド〕−３−（１−メ
チル−1H−テトラゾール−５−イル）チオメチ
ル−３−セフエム−４−カルボン酸483mgと３−
グアニジノプロピオン酸クロリド塩酸塩242mgを
実施例２と同様に反応させ化合物F267mgを得た。
元素分析値C19H24N12O5S3・H2O
計算値 C37.13、H4.26、N27.34
実測値 C37.34、H4.40、N26.75
NMRスペクトル（90MHz、D2O＋Py−d5の混液
中）δppm
2.82（2H、ｔ、Ｊ＝6.5Hz、グアニジノプロピオ
ニル２−CH2）
3.5〜3.8（2H、bro、２−Ｈ）
3.62（2H、ｔ、Ｊ＝6.5Hz、グアニジノプロピオ
ニル３−CH2）
4.05、4.07（3H、each、DL体によるテトラゾー
ル１−CH3）
4.32（2H、bro ｓ、３−CH2）
5.20、5.24（1H、each ｄ、Ｊ＝4.5Hz、DL体に
よる６−Ｈ）
5.66（1H、ｓ、チアゾールグリシン−CH）
5.76、5.88（1H、each ｄ、Ｊ＝4.5Hz、DL体に
よる７−Ｈ）
6.80、6.82（1H、each ｓ、DL体によるチアゾー
ル５−Ｈ）
IRスペクトルνKBr nax1765、1660cm-1
実施例 ７
化合物Ｇの製造
7β−〔DL−２−アミノ−２−（２−アミノチア
ゾール−４−イル）アセトアミド〕−３−〔１−
（２−ジメチルアミノエチル）−1H−テトラゾー
ル−５−イル〕チオメチル−３−セフエム−４−
カルボン酸454mgとグアニジノ酢酸クロリド塩酸
塩242mgを実施例２と同様に反応させ化合物G124
mgを得た。
NMRスペクトル（90MHz、D2O）δppm3.08
（6H、ｓ、ジメチルアミノ）
3.5〜4.0（2H、bro、２−Ｈ）
3.86（2H、ｔ、Ｊ＝６Hz、ジメチルアミノエチ
ル２−CH2）
4.18（2H、ｓ、グアニジノアセチル−CH2）
4.1〜4.4（2H、bro、３−CH2）
4.91（2H、ｔ、Ｊ＝６Hz ジメチルアミノエチ
ル１−CH2）
5.15（1H、ｄ、Ｊ＝５Hz、６−Ｈ）
5.63（1H、ｓ、チアゾールグリシン−CH）
5.69（1H、ｄ、Ｊ＝５Hz、７−Ｈ）
6.90（1H、bro ｓ、チアゾール５−Ｈ）
IRスペクトルνKBr nax1765、1670[Formula]) 3.2-4.0 (2H, bro, 2-H) 4.07, 4.09 (3H, each s, DL form of tetrazole 1-CH 3 ) 4.35 (2H, bro s, 3-CH 2 ) 5.72 (1H, s, thiazolylglycine CH) 5.81, 5.93 (1H, each d, J=5Hz, 7-H in DL form) 6.87, 6.90 (1H, each s, thiazole 5-H in DL form) IR spectrum ν KBr nax 1765, 1680, 1600, 1510 cm -1 Example 2 Production of compound B 7β-[DL-2-amino-2-(2-aminothiazol-4-yl)acetamide]-3-(1-methyl-1H-tetrazole 387 mg of -5-yl)thiomethyl-3-cephem-4-carboxylic acid was suspended in 6 ml of anhydrous acetonitrile, and then N,
O-bis(trimethylsilyl)acetamide 2
Add 2 ml of molar chloroform solution to trimethylsilylate, and then add 0.36 ml of propylene oxide. While stirring the reaction mixture under ice-cooling, 190 mg of 2-amidinoacetic chloride hydrochloride was added and stirred for 20 minutes. Furthermore, 190 mg of 2-amidinoacetic acid chloride hydrochloride was added and stirred for 20 minutes under ice cooling, and then 0.4 ml of propylene oxide and 190 mg of 2-amidinoacetic acid chloride hydrochloride were added.
Add mg. After stirring the reaction solution for 20 minutes, 2-
Add 140 mg of amidinoacetic acid chloride hydrochloride and stir for 20 minutes. Then, the reaction solution was returned to room temperature and stirred for 1 hour. Add 3 ml of water and 7 ml of tetrahydrofuran to the reaction solution.
ml of the mixture was added, the organic solvent was distilled off under reduced pressure, and the remaining aqueous layer was purified by passing it through an Amberlite XAD column to obtain 7β-[DL-2-(2-amidinoacetamide)-2-(2-amino thiazol-4-yl)
Acetamide]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-
4-carboxylic acid was obtained. 155 mg. Elemental analysis value C 18 H 21 N 11 O 5 S 3・H 2 O Calculated value C36.92, H3.96, N26.31 Actual value C36.59, H3.82, N26.01 NMR spectrum (90MHz, D 2 (in a mixture of O + Py-d 5 ) δppm 3.3-4.0 (2H, bro, 2-H) 4.06, 4.08 (3H, each s, DL form of tetrazole 1-CH 3 ) 4.35 (2H, bro s, 3-CH 2 ) 5.73 (1H, s, thiazolylglycine CH) 5.83, 5.93 (1H, each d, J=5Hz, 7-H with DL form) 6.85, 6.88 (1H, each, s, thiazole 5-H with DL form) ) IR spectrum ν KBr nax 1760, 1690, 1610, 1520 cm -1 Example 3 Production of compound C 7β-[DL-2-amino-2-(2-aminothiazol-4-yl)acetamide]-3-(1 -Methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (387 mg) and guanidinoacetic acid chloride hydrochloride (300 mg) were reacted in the same manner as in Example 2 to obtain 200 mg of Compound C. Elemental analysis C 18 H 22 N 12 O 5 S 3・H 2 O Calculated value C35.99, H4.03, N27.98 Actual value C35.70, H3.87, N27.67 NMR spectrum (90MHz, D 2 O + Py -d 5 ) δppm 3.3-4.2 (2H, bro, 2-H) 4.07, 4.09 (3H, each s, DL form of tetrazole 1-CH 3 ) 4.33 (4H, bro s, 3-CH 2 and Guanidinoacetyl- CH2 ) 5.75 (1H, s, thiazolylglycine-CH 5.84, 5.94 (1H, each d, J = 4.5Hz, 7-H with DL form) 6.87, 6.90 (1H, each s, DL form Thiazole 5-H) IR spectrum ν KBr nax 1765, 1670, 1520 cm -1 Example 4 Preparation of compound D 7β-[DL-2-amino-2-(2-aminothiazol-4-yl)acetamide]-3 -(1-Methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid 387mg and 2-
(3-Methylguanidino)acetic acid chloride hydrochloride 460
mg was reacted in the same manner as in Example 2 to obtain 245 mg of Compound D. Elemental analysis value C 19 H 24 N 12 O 5 S 3・H 2 O Calculated value C37.13, H4.26, N27.34 Actual value C37.42, H4.49, N27.08 NMR spectrum (90MHz, D 2 (in a mixture of O + Py-d 5 ) δppm 2.97 (3H, s, guanidine 3-CH 3 ) 3.2-4.1 (2H, bro, 2-H) 4.04, 4.06 (3H, each s, tetrazole 1-CH 3 in the DL form ) 4.25 (4H, bro s, 3-CH 2 and guanidinoacetyl CH 2 ) 5.19, 5.28 (1H, each d, J = 4.5Hz, 6-H with DL form) 5.66 (1H, s, thiazolylglycine CH ) 5.74, 5.84 (1H, each d, J = 4.5Hz, 7-H in DL form) 6.80, 6.82 (1H, each s, thiazole 5-H in DL form) IR spectrum ν KBr nax 1760, 1665, 1515cm - 1 Example 5 Preparation of Compound E 7β-[DL-2-amino-2-(2-aminothiazol-4-yl)acetamide]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3 -Cefem-4-carboxylic acid 387mg and 2-
400 mg of (imidazolin-2-yl-amino)acetic acid chloride hydrochloride was reacted in the same manner as in Example 2 to obtain 150 mg of compound E. Elemental analysis value C 20 H 24 N 12 O 5 N 3・H 2 O Calculated value C38.33, H4.18, N26.82 Actual value C38.21, H4.02, N26.34 NMR spectrum (D 2 O + Py− d in a mixture of 5 )
δppm 3.79 (4H, s, imidazoline-CH 2 -CH 2 -) 4.03 (3H, s, tetrazole 1-CH 3 ) 4.02 (4H, bro, 3-CH 2 and (imidazoline-
2-yl-amino)acetyl CH 2 ) 5.23 (1H, 6-H) 5.60 (1H, s, thiazolylglycine CH) 5.83 (1H, 7-H) 6.80 (1H, thiazole 5-H) IR spectrum ν KBr nax 1765, 1675, 1600, 1515 cm -1 Example 6 Production of compound F 7β-[DL-2-amino-2-(2-aminothiazol-4-yl)acetamide]-3-(1-methyl-1H -tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid 483 mg and 3-
242 mg of guanidinopropionic acid chloride hydrochloride was reacted in the same manner as in Example 2 to obtain 267 mg of compound F. Elemental analysis value C 19 H 24 N 12 O 5 S 3・H 2 O Calculated value C37.13, H4.26, N27.34 Actual value C37.34, H4.40, N26.75 NMR spectrum (90MHz, D 2 In a mixture of O + Py-d 5 ) δppm 2.82 (2H, t, J = 6.5Hz, guanidinopropionyl 2-CH 2 ) 3.5-3.8 (2H, bro, 2-H) 3.62 (2H, t, J = 6.5Hz, Guanidinopropionyl 3- CH2 ) 4.05, 4.07 (3H, each, DL form of tetrazole 1- CH3 ) 4.32 (2H, bros, 3- CH2 ) 5.20, 5.24 (1H, each d, J=4.5Hz, 6-H by DL form) 5.66 (1H, s, thiazoleglycine-CH) 5.76, 5.88 (1H, each d, J=4.5Hz, 7-H by DL form) 6.80, 6.82 (1H, each s, DL form Thiazole 5-H) IR spectrum ν KBr nax 1765, 1660 cm -1 Example 7 Preparation of compound G 7β-[DL-2-amino-2-(2-aminothiazol-4-yl)acetamide]-3-[ 1-
(2-dimethylaminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-
454 mg of carboxylic acid and 242 mg of guanidinoacetic acid chloride hydrochloride were reacted in the same manner as in Example 2 to obtain compound G124.
I got mg. NMR spectrum (90MHz, D2O ) δppm3.08
(6H, s, dimethylamino) 3.5-4.0 (2H, bro, 2-H) 3.86 (2H, t, J=6Hz, dimethylaminoethyl 2-CH 2 ) 4.18 (2H, s, guanidinoacetyl-CH 2 ) 4.1-4.4 (2H, bro, 3-CH 2 ) 4.91 (2H, t, J = 6Hz dimethylaminoethyl 1-CH 2 ) 5.15 (1H, d, J = 5Hz, 6-H) 5.63 (1H, s, Thiazoleglycine-CH) 5.69 (1H, d, J=5Hz, 7-H) 6.90 (1H, bros, thiazole 5-H) IR spectrum ν KBr nax 1765, 1670
Claims (1)
を示すか、R1およびR2で非置換アルキレン基を
示し、R3およびR4はＨを示し、ｎは１を示し、
ｍは０または１を示し、ｚは非置換アルキレン基
を示し、R5は低級アルキルもしくは置換アルキ
ル基が置換することもある異種原子含有五員環を
示す〕 で表わされるセフアロスポリン誘導体またはその
塩。[Claims] 1. General formula [In the formula, R 1 and R 2 represent H or a lower alkyl group, or R 1 and R 2 represent an unsubstituted alkylene group, R 3 and R 4 represent H, n represents 1,
m represents 0 or 1, z represents an unsubstituted alkylene group, and R 5 represents a five-membered ring containing a heteroatom which may be substituted with a lower alkyl or substituted alkyl group] or a salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6857079A JPS55160783A (en) | 1979-06-01 | 1979-06-01 | Cephalosporin derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6857079A JPS55160783A (en) | 1979-06-01 | 1979-06-01 | Cephalosporin derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS55160783A JPS55160783A (en) | 1980-12-13 |
| JPH0121153B2 true JPH0121153B2 (en) | 1989-04-19 |
Family
ID=13377552
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6857079A Granted JPS55160783A (en) | 1979-06-01 | 1979-06-01 | Cephalosporin derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS55160783A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5088091A (en) * | 1973-12-10 | 1975-07-15 | ||
| JPS5248684A (en) * | 1975-09-08 | 1977-04-18 | Squibb & Sons Inc | Production of ureidocephalosporin derivative |
| JPS6058239A (en) * | 1983-09-07 | 1985-04-04 | Sumitomo Metal Ind Ltd | Coal liquefying catalyst and preparation thereof |
-
1979
- 1979-06-01 JP JP6857079A patent/JPS55160783A/en active Granted
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5088091A (en) * | 1973-12-10 | 1975-07-15 | ||
| JPS5248684A (en) * | 1975-09-08 | 1977-04-18 | Squibb & Sons Inc | Production of ureidocephalosporin derivative |
| JPS6058239A (en) * | 1983-09-07 | 1985-04-04 | Sumitomo Metal Ind Ltd | Coal liquefying catalyst and preparation thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS55160783A (en) | 1980-12-13 |
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