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    • 专利摘要:
    Antibiotic activity is exhibited by beta -lactams having an <IMAGE> substituent in the 1-position and an acylamino substituent in the 3- position, R<5> and R<6> being hydrogen atoms at various defined substituents or R<5> and R<6> together completing a ring. The corresponding 3-amino compounds may be produced as intermediates. The compounds may be of the formula:- <IMAGE> or salts or esters thereof, R1 being hydrogen or acyl and R2, R3 and R4 being hydrogen atoms or substituents.
    公开号:SU1318146A3
    申请号:SU833652346
    申请日:1983-10-05
    公开日:1987-06-15
    发明作者:Аллен Слузарчик Вильям；Рой Кроненталь Давид
    申请人:Е.Р.Сквибб Энд Санз,Инк. (Фирма)；
    IPC主号:
    专利说明:

    t13
    The invention relates to a process for the preparation of azetidinylsulfonic acid derivatives of the general formula:
    3
     R - NH.i.I
     2,
    Q -K - OCH - SO-jH.
    where Rj is hydrogen or acyl selected from the group
    Cj. AIX - N- (N-CO-- NH-CH-co / H,
    oh oh
    or
    H, NV
    where R is hydrogen or C, -C-alkyl,
    possibly substituted by carboxylic acid or its ester;
    R and RJ are individually hydrogen or C-C4-alkyl5 or their alkali salts, which have antibacterial activity.
    The aim of the invention is to obtain new compounds with high pharmacological activity.
    The method is implemented as follows, and in a manner.
    PRI me R 1. A) 3S- / 3a {Z), (2-amino-h-thiazolyl) -2-- / A-methyl-2-oxo-1- (sulfomethoxy) -3-azetidinyl (-) amino. -2- oxoethylidene / a-gano zoxo) -2-methylpropanoic acid, dipotassium salt.
    A) Aminoxymethans ly)) acid.
    Adetonoxime (1.46 g, 20 mmol) is added to a suspension of 60% sodium sulfate dispersion (0.8 g, 20; gmol) in mineral oil in 16 ml of dry dimethyl sulfoxide. Then (add portions of bromine to 1 tetanus: 1 phon: sodium (3–94 g, 20 mmol). The reaction mixture is heated at 90–9.5 ° C for 4 hours under nitrogen atmosphere, cooled, washed and washed twice with 250 ml of simple ether. After solidifying the product, it is washed with 100 ml of dichloromethane, filtered and dried over phosphorus pentoxide to obtain 15.3 g of an unclean substance. This substance is dissolved in 20 ml of water and tetrabutylammonium sulphate (7, 5 g, 22 mmol.) The resulting product with a paired ion extractor lot two times
    1462
    AP: 200 P-1P dichloromethane. Dichloromethane solution of sodium sulfate over sodium sulfate and condenser lot in vacuum. The hydrolysis of acetone oxime l. Is achieved by heating in 120 ml of 2 k. HC1 at 130 ° C for - h. This solution is concentrated in vacuo: it is mixed twice, and then from acetonitrile. The product hardens after adding
     dichloromethane. It is filtered and dried in a vacuum to obtain 2.5 g of the title compound.
    c) O-Sulfomethyl-o -Y-tert-butoxycarbonyl-1g-threonine 1 1- | Droxamat, kalier a: c ol.
    ; M1-Gnoxmethanesulfonic acid (1sl4 g, 8.9 mmol) addition; g; m to a solution of tert-bu tocarbonyl-1 - t of eonine (g, 8.9 no.) in 16 ml of iodine and 4 ml of tetra-1 and: drofurag1a at 0 ° C. The pH was adjusted to 4j5 with 1N KOH and g-: methyl-3-v3-dimethyl-aminopropyl) carbodimmy d-hydrochloride (1, 87 g, 9.7) in 8 ml of water was added dropwise. The reaction mixture, G1er; n-1, is held at ambient temperature for 2 hours while the pEi value is maintained at a differential 4-ij5, periodically added with 1 n hydrochloric acid. ) The product is ionized: paired with: acidic sulphate tererabutylam1 — they (3.05 g, 8 mmol) at a pH of 2; 8 and extracted four from an aqueous solution; in portions of 1 00 ml of dichloromethane. Dicht ormethane
    35 solutions of dried su, pef, 1 ton of sodium and chondenturized in Haxi yi-iOj to obtain 4.5 g of the product of the i.che tegrabutylammonium salt. converted into potassium salt with pomo; c) u io);
     150 ml pitch: Daux 50 x (0.7 mEq) and after about 1 2 2 662 g of product,
    C) Tetrabutyl; - () nium salt 0- -sulfomethyl r / - tv- gret-butyoxy carbo - -1IL-b- (0-meta11g Ufony: 1T1K; ONin) hydrococ with a mat but .
    71
    thirty
    To a part of 1 salt of iron;
    0 - S-tert-bucket X 2 J 3 7 g. 6) pyridine npii added; 4-tansulfs-p-1
    5 (the temperature in the center-turn is set to O Decrease 2 "O
    mu rg: with a potassium-borne m a t C1 - with a l u ff ome til - (sikarHypil-b-threonine I. iMonf,) in 50 k dry in a nitrogen atmosphere drops: 0; 8 ml (10 ml) ihlpda . Reactionary wilted at room temperature for 4 h; and then in vum kume. The residue is ra- ml (odes and at pH 2.8 g (6 mmls) of acidic
    3131
    tetrabutylammonium sulfate. The ion-paired material is extracted with chloroform. The chloroform solution was dried and concentrated in vacuo to obtain 2.7 g of crude product.
    D) The potassium salt of 3S- (3c, 4B) J- (1,1-dimethylethoxy) carbonyl / - -amino-A-methyl-2 oxo-1- (sulfomethoxy) azetidine.
    The tetrabutylammonium salt of 0-sulfomethyl-o -Y-tert-butoxycarbonyl-L- - (0-methanesulfonyltreonine) hydroxamate (2.6 g, 4.0 mmol) is dissolved in 5 ml of acetone and added dropwise to heated under reflux suspension of 2.2 g of potassium carbonate in 65 ml of acetone. Heating under reflux is continued for 3.5 hours and the reaction mixture is cooled, filtered, and concentrated in vacuo. The residue is dissolved in 10 ml of 0.5 M KH, ROD at pH 5.5, the pH value is adjusted to 2, 8, The product is extracted four times with 100 ml portions of dichloromethane. The combined extract is dried and concentrated in vacuo to obtain 1.52 g of crude ion-paired tetrabutylammonium beta-lactam salt. The potassium salt is obtained by ion exchange using 50 MP Daux 50 x (0.7), to obtain, after lyophilization, a crude substance, which is further purified by chromatography over 00 ml of HP-20 using water. The appropriate fractions are lyophilized. A yield of 0.245 g of product is obtained.
    Calculated: C 32.46, H 5.28; 7.57-, S 8.66.
     H, Nj07SK-1, 2H20
    Found: C 32.52-, H 4.76, N 7.43, 8.30.
    E) t3S- (3o /, 4B) -1-sulfomethyl-3-mino-4-methyl-2-oxo-1-azendin.
    The potassium salt of 3S- (3oi, 4c) -3-C / (1, 1-dimethylethoxy) carbonyl / aminoT-4-methyl-2-oxo-1- (sulfomethoxy azetidine (0.245 g, 0.68 mmol) is suspended in 0.5 ml of dichloromethane and 0. 5 ml of anisole. The reaction mixture is cooled to 0 ° C and trifluoroacetic acid (1.0 ml) is added under nitrogen atmosphere. The reaction mixture is stirred, it is added for 1 hour and then concentrated in vacuo to a residue, co-1 cakes are evaporated from benzene twice. This substance is triturated with ether
    64
    and the ether is decanted to give the desired product as a white solid.
    F) Potassium salt of diphenylmethyl alcohol 3S- / 3c (Z), 4B / J-2-r // 1- (2- - aMiiHo-4-THazolyl) -2 // 4-methyl -2-oxo- -1 - (sulfomethoxy) -3-azetidinyl / amino-2-oxo-ethylidene / amb / oxy / -2- -methyl propionic acid.
    (Z) -2-amino-cc- / 2- (diphenylmethoxy) -1,1-dimethyl-2-oxo-totoxy / -imo-thiazoleacetic acid (0.30 g, 0.68 mmol) and 1-hydroxybenzo triazole hydrate (0.10 g, 0.68 mmol) is dissolved in 4 ml of dry dimethylformamide in a nitrogen atmosphere. This substance is cooled to O C, and N, N -dicyclohexylcarbodiimide (0.14 g, 0.68 mol) is added to the flutters. After the Compressor is pressed, the reaction mixture is stirred at O C for 1 hour. To the mixture is added a solution 3-amino-1- - (sulfomethoxy) azetidine (approximately 0.68 mmol) in 10 ml of dimethylformamide and 0.5 ml of N, N -diisopropyl-ethanol at 0 ° C. The reaction mixture was stirred at 0 ° C for 1 hour and then at room temperature overnight. The solution is filtered and
    the filtrate is concentrated in vacuo. The residue is dissolved in 50 ml of dichloromethane and washed with 2 ml of water. After evaporation of dichloromethane, 0.372 g of crude product is obtained. This product is passed through 30 ml of Dousex 50x (0.7 mEq) using water to obtain, after freeze-drying, 0.211 g of crude product: contaminated with hydroxybenzotriol ash.
     G) Dikaliev salt 3S- / 3e (Z), (2-amino-4-thiazolyl) -2- - // 4-methyl-2-oxo 1- (sulfomethoxy) -3-azetidincle / amino -2-oxoethylidene / amino / oxy / 2-methylpropanoic acid

    you.
    Potassium salt of diphenylmethyl ester 3S- / 3oL (Z), (amino- - 4-thiazolyl) -2 - // - 4methyl - 2-oxo-1- - (sulfomethoxy) -3-az etidine-sh / Amino-2-oxo-ethynes, en / amino / oxy / -2-methyl-propionic acid (0.211 g) is dissolved in 1.8 ml of dichloromethane, 0.5 ml of anisole and 1.5 ml of trifluoroacetic acid and stirred under nitrogen atmosphere at 2 hours. The reaction mixture is concentrated in vacuo and evaporation twice from benzene. The residue is washed with a mixture of ether with ethyl acetate
    513
    volume (1: 1) and a mixture of ether and acetonitrile (1: 1) to give a white solid. This substance was dissolved in 1.0 ml of 0.5 M KHjPO ,, at pH 5.5, adjusted to pH 6.5 with 1 n KOH, and chromatographed over 40 mp of HP-20 using water to obtain 43 mg of the title compound. melting point 200 ° C (dec,).
    Calculated: C 28 ,, H N 11.85i S 10.84.
    C H N OjSjK - 2.75HjO.
    Found: C, 28.32 J H., 36; M 11.90; S 10.37.
    Example 2. 2S- / 2, 3B (Z) / J - / 3 - / / (2 - amine O-4-t and a 3 ol i.p) - (m OK OK syimino) acetyl / amino -2 - meth - n-4-oxo--1-azetidinyl / hydroxy / methanesulfonic acid.
    Following the procedure of Example 1 and the replacement of the thiazoleacetic acid used in Part F of Example 1 j with an equimolar amount of (2) -2-amino-c / - / (methoxy) -imino / -4-thiazoleacetic acid, the desired compound is obtained in the form of a monopotassium salt, which is a hygroscopic solid after dissolving in aceto-nitrile and removing acetypitrile with no / i vacuum several times.
    HK-SO; H1030 cm-) beta-lactate, 1 m (1778).
    Calculated: C 38, 11 H 4.82; N 15.92; S 12,5.
    С Н NjOvSzK -О,.
    Found: C, 37.94; H 5.36; N 15.92 S 12.56.
     Example 3. 5- / 2. {,, ЗВ (F;) / - / 3 - //// (4-ethyl-., З-dioxo-1-lipidrazinil) carbonyl / -amino / phenylacetyl / - amino -2-methyl-4-oxo-1 -az ethidine nor l / - hydroxy / methane sul-1. acid.
    Following the procedure of Example 1 and replacing
    In part F of Example 1, l - // (4- -ethyl-2 5 W-dioxo-1-piperazipyl) carbonyl / amino / -phenylacetic acid: lot, the desired compound is obtained in the form of monopotassium sogi, which is hygroscopic solid brittleness, IR-SO (1038 cm); beta-lactam (1175 cm-).
    Calculated: C 41.53-, H 4.74; N 12.11, S 5.54.
    С (, H, j4 NjOgSK -1,6Н, 0.
    Found: C 41.53, H 4.46; N 11.13; S 5.61.
    Example 4, (S) -3-5enzyloxycarbonyl1 (thyl -2-oxo-1 - - (sulfomethoxy)) ag-e tidnn.
    Following the procedure 1: € of Example 1, chasm AD, and the replacement of treg-butoxycarbonyl-1.-threonine used in the Pj part, benzyloxycarbomyl serine, the target appendix is obtained in the form of a ca-:; ivium salt, HK- SOj (1025 cm-); Beta-lactam (1 7 7 5 cm).
    Following the procedures described by Pahr, a trace of lean connections is prepared:
    (ZZ-trans- / (2-amino-4-thiazolyl) - (methoxyimino) acetyl / amino / -4-methyl- - 2-oxy-1 -azetidinyl / oxy / methanesulfonic acid, monocarbonate salt,
    (3S-trans) -G / (2-I I: -1o-4-thiazolyl) / (2.2, 2-trif Tor: 5toxy) imino / acetone / - gmino / -4-methyl-2-oxo -1-azetidinyl / - (: to with and / m et a and with y and j: о o about and with: t about t, -i. M about about and a and e - yy and o ол;
    2.5
    V. - -amino-4-thia3olyl j
    (3S-TpaHc) -r / (: (2-a gyno-2-oxoet C Xi) imino / acetyl / amino / -4-met51l-2-scso-1 -azetidinyl oxy / methane ulfacid (Monorsalieva
     /. - () to c (1 - 1 - a h -3 t id and nil / - o to c and /; cetisul.ofoctgsl;) Th, dikklcheva salt (35-trance - // (2-ymino-4 -thiazolyl) (1 carbox or klsprop L) -oxy / nmino /
    40
    g and 11 pl, / o k s and / - e T a i c l teff oxide l o t a, D and k aliyev c (5l;
     3 L - / 3 ci (I,;, 4 V / - / / 3 - G (amine of nyl-acetyl) amine; -, -4-Mstil-2-oxo-1-acetyl / oxy / ke- Hachsulfonic acid S monocapium coj b,
     3- (fechilacetil) ami 3- (Z-thienyl-apetil) - i-h: hcc) -azetidinyl / oxy / methang ul, f (); urea-salt;
    (3Z-trans,: - / / 3 (2 f) -dimethoxyfep- | yl) auBTS-iJ / fiMHH,; / - i -me GIL-2-OKSS-1 - - azetidi}) L / oxm / vc; an : ul1 phacid 5 monokalievy;: rj: i,
    GZy- / Zg. (K;, DV / - 3 - // // Gam-1No-Kg rbonite) amkno-2-HH epylacetyl-amino / 4-methyl-2-ox;) - 1 - azetidinyl / ok- c: i / meta1; su, 1: (fs) kis uta, my local coalition;
    713181468
    3S- / 3a ((R), 4B / -C / 3 - / (carboxy-2-ox-1-azetidnyl / hydroxy-metaculphenylacetyl) amino-4-methyl-2-oxo-1-acid, monopotassium salt ,
    (ZZ-cis) - // {2-amino 4-thiazolyl) (2,2,2-trifluoroethoxyimino-acetyl / amino / -4-meth-eth-2-oxo-1-acetidine / hydroxy methanesulfonic acid, monopot-azetidinyl) hydroxy / methanesulfonic acid, dipotassium salt;
    3S / 3ot (J), 4B / -G / 3 - / (phenylsulfo-5 acetyl) amko-J-4-methyl-2-oxy-1-azethidinyl / oxy / methyl sulfonic acid, dicalium salt;
    (3Z-trans) (2-amino-4-thiazolyl) oxo-acetyl / amino / -4-methyl-O-2-oxo 1-azetidinyl / hydroxy methanesulfonic acid, monopotassium salt;
    t3S- / 3c / (R) 4fi / -f / 3 - /. //// 2-OKco-3- (phenylmethylene) amino -1-imidazole (33-cis) (2-amino-4-thiazolyl) (carboxymethoxy) imino acetal 1 / -amino / 4-methyl-2-oxo-1-azetidinyl / hydroxy methanesulfonic acid, dipotassium salt;
    (3Z-cis) (2-amino-4-thiazolyl) (1-carboxy-1-methylethoxy) -imino / acetyl / amino ./- 2-OXO-4-methyl-1 dinyl / carbonyl / amino / phenylacetyl / am- 5 -azetidinyl / hydroxy-meta-sulfonic acid,
    but-4-methyl-2-oxo-1-azetidinyl / okadyl salt;
    si methanesulfonic acid, monokaliev (ZZ-cis) (2-amino-4-thiazolyl)
    salt-,
    r33- / 3t / (Z), 4B / - / 3-G / 2-furanyl
     (1-pcarboxycyclopropyl) oxy-ish-1- but acetyl / amino-4-methyl-2-oxo-1 (methoxyimino) acetyl / amino,} - 4-methyl-20 -azetidinyl / oxy / methanesulfonic acid, -2- OXO-1 - azetidinyl / hydroxy methanesulfur. Alcohol;
    phacic acid, monopotassium salt; (3-3-cis) -I / (2-amino-4-thiazolyl)
    33 (Z) - / 3 - // (2-amino-4-thiazo-G (2-amino-2-oxethoxy) imino-acetyl / amino-4-methyl-2-oxo-1-azetidilyl) (methoxyimino) acetyl / amino / -2oxo-1-azetidinyl / hydroxy methanesulfonyl / hydroxy / methanesulfonic acid, monoacid 3) monopotassium salt,
    33 (Z) j - G / 3 - // (2-amino-4-thiazolyl) (1-carboxy-1-methylethoxy) -imino acetyl / amino / -2 ox-1-azetidinyl / hydroxy / methanesulfonic acid, decal salt ;
    r33 (Z) j - / 3 - // (2-amino-4-thiazolyl) 2,2, 2-trifethopathoxy and Jino / -acetyl / amino / -2-ox-1-azetidinyl / hydroxy methanesulfonic acid, monopotassium salt;
    33 (Z) - / 3 - // (2-amino-4-thiazolyl) (2-amino-2-oxoethoxy) imino acetyl / amino / -2-OXO-1-azetidinyl / oxy
    ; ol;
    methanesulfonic acid, monopotassium salt; 0 si / methanesulfonic acid, monokaliev
    (S), 4B - / 3 - /// (aminocarbonyl) amino -2-thienylacetyl / -ami-HO / -2-OXO-1-azetidinyl / hydroxy methanesulfonic acid, monopotassium salt;
    33- (3); (R), df — G / 3- (aminophenyl acetyl) amino 1-4-methyl-2-oxo-1-azetidinyl / hydroxy methanesulfonic acid, potassium-potassium salt.
    (t), / 3- (phenylsulfopaacetyl) amino / -2-oxo-1-azetidinyl / oxy methanesulfonic acid, dikalieva. salt;
    (K), 4B - / 3 - //// (4-ethyl- -2 5 3-dioxo-1-piperazinyl) -carbon.yl aNJHHo / phenyl acetyl / amine / -2-oxy o-1-azetidinyl / hydroxy methanesulfonic; mono potassium salt
    33 (Z) (f.noxyacetyl) amino -2-ox o-1 -azetidinyl / -oxy / methanesulfonic acid 5 monopotassium salt,
    (Z3-cis) (2-amino-4-thiazolyl) (methoxy-shno) acetyl / ai Gino / -4-methyl-;
    (33-cis) (2-amino-4-thiazolyl) (carboxymethoxy) imino acetoxy 1 / -amino / 4-methyl-2-oxo-1-azetidinyl / hydroxy methanesulfonic acid, dipotassium salt;
    (3Z-cis) (2-amino-4-thiazolyl) (1-carboxy-1-methylethoxy) -imino / acetyl / amino ./- 2-OXO-4-methyl-1 (1-psarboxycyclopropyl) hydroxy-ish-1- but acetyl / amino-4-methyl-2-oxo-130
    molten salt
    3S- / 3o / (R), 4ci / -C / 3- (carboxy-phenylacetyl) amino-4-methyl-2-oxo-1 -azetidinyl / hydroxy methanesulfonic acid,
    dikaliev salt;
    t33- / 3o ((R) -, 4c; / -H / 3- /// (4-ethyl--2, 3-dioxo-1-piperazinyl) -carbonyl accno-phenylacetyl amino-4-methyl-2- - oxo-1-azetidinyl / -oxy methanesulphonic acid, 35 mono potassium salt;
    3S- / 35 / (3), 4e / -H / 3 - /// (aminocarbonyl) amino -2-thienylacetyl / amino / -4-methyl-2-oxo-1 -az etidinyl / ok; sol;
    33- (3); (R), df — G / 3- (aminophenyl-acetyl) amino-1-4-methyl-2-oxo-1-azetidinyl / hydroxy methanesulfonic acid, potassium salt.
    The preparation of the compound can be used as agents to kill bacterial infections,
    Q Includes urinary tract infections and respiratory tract infections. In tab. 1 and 2 presents data on the antibacterial a; - :: tyBNOSTy of compounds I in determining the minimum inhibitory concentration (MIC) required against various microorganisms (Table 1), as well as comparative analysis data (Table 2) in comparison with the compound the prototype.
    9131
    against fl-lactamase producing organisms.
    Ph o I) m u l a and 3 o b e te; i-: to
    Method for preparing azethidinyl sulfonic acid derivatives of general formula I
     , HF
    .-i..F |
    I r
    O.J -N -OCH, - ™
    f-SCHN.
    where R is hydrogen or acyl selected from the group
    AIKт w ™
    CO-NH-CH-CO
    with "n
    or.
    - Q with H2K-i.gJ N-OK ,,
    where R. is hydrogen or C., - C, -alkyl,
    possibly substituted by carboxylic acid or marshmallow.
    ABOUT
    R and R, - each separately hydrogen or s, -C - alk: silt 5 or their alkaline salts, about tl and h and w. and with the fact that the connection obsh.ey formula:
    : i.
     C-CH -.H- R
    I i
    .c - FiM-oCH - SOjH
    10 where R is hydrogen;
    Rj and R- - have the indicated values or its salt, is cyclized with; using a base; such as potassium carbonate, in an organic solvent; 1.5, such as acetone, at a temperature; / reflux, with separation of compound 1, where R. - hydrogen, or with subsequent concern with common acid
    20 formulas:
    25
    where R has the indicated values for
    acyl,
    Presence: Ш carbodiimide and injection of the target product in free zide or in the form of alkaline salts.
    G a b l and c a 1
    eleven
    1318146
    12 Continuation of the table: 1
    Note The number of units of the microorganism colony formed
    in ml medium (CFU) is 10.
    table 2
    Note
    Culture} zypa111,1-izayut in staggartnoy agar medium - Ag a g D i with i p o c and i a
    CFU - 4i Cj:; o obra: uyushar from a microorganism colony in MJI sredV) agar.
    Compiled by I. Bocharova Editor A. Lezhnin Tehred N. Glushenko
    Order 2439/57 Circulation 372
    VNRVDPI USSR State Committee
    for inventions and discoveries 113035, Moscow,} (- 35, Raushsk: nab. 4/5
    . Production and Printing Preg., Uzhg-Orol, ul., Design, 4
    ) peKTOp V. Booth ha
    G: ODG ISNOE
    权利要求:
    Claims (2)
    [1]
    A method of obtaining derivatives of • thidinyl sulfonic acid of the general formula where R 1 is hydrogen or acyl selected from the group / ““ X - K ^ -CO-KI-CH or
    R and - each separately hydrogen or C t ~ C 4 ~ alkyl, or their alkaline salts, characterized by the fact that the compound of the general formula: he
    R ^ NH-CH-C-P 4
    I ' R i „С - mn-OCH, - SO, Н
    O 2 3 where R 1 is hydrogen;
    Rj and Rj - have the indicated meanings, or a salt thereof, subjected to cyclization using bases; such as potassium carbonate in an organic solvent such as acetone at reflux temperature to isolate compound I, where R. - hydrogen, or followed by treatment with an acid of the general formula:
    R is OH.
    b where R, has the indicated meanings for acyl, in the presence of carbodiimide and the liberation of the target product in free form or in the form of alkaline salts.
    Table 1
    Microorganism Number is- MIC, μg / p, compounds following the exampleexperienced - -----------------------------— - ------------------- -------------- at the office 2 h 1G oneSquibb ------------------ V ------------ of culture R 2 , R r —CH j;R , R.-CH R. - Ru- 2-methyl acetyl, - propanoil wild dipotassium salt salt - - - - -- E. col i 8294 6.30 0.40 0.40 s / o 3.10 10857 0/0 0.10 0.05 0.80 0.80 _> 1 _ 10896 12.50 0.40 0.20 0, a0 0.80 _Π_ 10909 0.80 0.10 0 „05 c / o 0.80 K.aerogenes 10440 s / o 0.40 0.4 C 0.30 3.10 K, pneumoniae 9527 0.80 0.20 0.05 1,60 0.80 Frot.mirabilis 3855 3.10 ί u ’ 0.05 1,60 0.30 Frot. rettoeri 84 79 1, 60 0,0 5 0.05 0, 1 0 0.05 Frot.vulgaris 9416 o / o 0.10 0.05 0.05 0.40
    Continuation of the table. one
    Microorganism
    The number of technical / guided by the company. Squibb culture μg / ml, the compounds of example ^ 2., 8-3;
    R "_- .. acetyl, dicalne salt
    R ^ CHj;
    [2]
    2-methyl propanoyl, dipotassium salt
    Sal.typhosa 1 195 1,60 0.10 0.05 0.40 0.40 Shig.sonneί 8449 6.30 0.40 0.40 3.10 1, 60 Ent. cloacae 8836 6.30 0.40 0.20 1,60 1,60 Ent. aerogenes 10078 '25.00 0.80 0.80 3,1 3.10 Citro.froundii 9518 6.30 0.40 . 0.40 1,6 0.80 Ser.macoeseens 9783 6.30 0.40 0.20 1,6 0.80
    Note The number of units of the resulting colony of the microorganism in ml medium (CFU) is 10 *.
    table 2
    MIC, μg / ml, compounds Microorganism2 ''Suggested x - -och 2 -so 5Famous X - -so- at CFU 10* 10* onei- oneΟ 1oneone 10 s E.coli TEM +10404 0.2 0.4 25 one hundred E.coli TEM-10439 0.4 0.4 ' 02 08 Ent ', cloacae P99 + 10435 > 100 7100 7100 7100 JSnt. cloacae P99- 10441 0.2 . 0.4 ΙΊ Oh ο, Ζ 0.4
    I4
    Continuation of Table 2
    Microorganism in CFO
    Famous X - -SOj
    MIC, μg / ml, compounds
    Proposed
    X - -OCHj-SOj
    K. aerogenes K1 + 10436 6.3 fifty > 100 > 100 K. aerogenes K1- 10440 0, 1 about/ 0.2 0.8 K. pneumo 1 106 6 0.8 Ί1 j V one hundred > 100 FROM . ireundii 10204 0.4 fifty 0.8 25 Prot. rettgen 8217 2 0,05 <0.05 <0.05 . 0.2 Prot. vulgaris 109518 i'0.05 <0.05 0/1 0.8 Ser. marcescens 9 78 2 0.2 I ί 0.4 1L Ps. aeruginosa 8329 6.3 1.2 L 3,1 6.3 Ps. aeruginosa 9545. 16 ί L - - --------—----——------------- - ---------------- --------_ - Note : Vyra cultureAgar Die iaoc> pinch in st;.'La; 1 nlartn- oh agar environment CFU is the number e.,nizma in cynic image:ml ai medium uyugpeys./ ara> I'm a colony micror
    Compiled by I. Bocharova
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US4337197A|1980-10-31|1982-06-29|E. R. Squibb & Sons, Inc.|O-sulfated β-lactam hydroxamic acids and intermediates|EP0135194A1|1983-09-16|1985-03-27|Takeda Chemical Industries, Ltd.|Azetidinones and their production|
    WO1985004876A1|1984-04-24|1985-11-07|Takeda Chemical Industries, Ltd.|2-azetidinone derivatives and process for their preparation|
    US4581170A|1984-08-03|1986-04-08|E. R. Squibb & Sons, Inc.|N-hydroxyl protecting groups and process and intermediates for the preparation of 3-acylamino-1-hydroxy-2-azetidinones|
    JPH0649710B2|1984-08-06|1994-06-29|藤沢薬品工業株式会社|Azetidinone derivative and method for producing the same|
    UY34585A|2012-01-24|2013-09-02|Aicuris Gmbh & Co Kg|B-LACTAMIC COMPOUNDS REPLACED WITH AMIDINE, ITS PREPARATION AND USE|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US43317582A| true| 1982-10-06|1982-10-06|
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