• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    METHOD FOR OBTAINING COMPLEX BI.S-ETHER METHANDIOL WITH PENICILLANIC ACID DERIVATIVE AND 1,1-DIOXIDE PENICILLANO ACID FORMULA .0 NCS CHS | II o I och, o ozS / snz} N /, Q II o characterized in that the compound of the formula CO QcH-co-i H,.-H rtHfcH3 LN-vC - NH, O Oh sn,., CH3 I G ngSnz IN-, CC-0 and o in the c-form is subjected to interaction with acetone.
    公开号:SU1122229A3
    申请号:SU823394406
    申请日:1982-02-24
    公开日:1984-10-30
    发明作者:Чарльз Кроуфорд Томас；Склавонос Константин
    申请人:Пфайзер Инк.(Фирма)；
    IPC主号:
    专利说明:

    11 The invention relates to a method for producing a new antibiotic of the penicillin series, namely a bis-ester of a methanedol with a penicillanic acid derivative and a 1,1-dioxy penicillanic acid of the formula I / - / S. Snf Hrf NTf CHj About o - oh II This can be used as an antibacterial agent in medicine. A known method for the preparation of the bis-ester of methanediol with a penicillanic acid derivative and .1,1-di-oxide of penicillanoic acid of the form I, -f-afcHs CH-CO-NHn IN-vC - 0 0 / CM, f-HpCHs I a) -form, which implies that the corresponding D-azidopropyl or protected D-amino derivative undergoes catalytic hydrogenolysis or hydrolysis 1. The compound of formula (II) is active against penicillinase-producing bacteria. The purpose of the invention is to obtain new penicillin antibiotics possessing activity against the bacteria producing penicillinase. The goal is achieved based on the reaction of 6- (2-phenyl-2-1) -aminoacetamido) -penenes of cyllines with acetone 2, which is known in organic synthesis, by the method of obtaining the bis-ester of the methandiol of the formula (l, which means that the bis-ester of the methanediol of formula (II) in B-form, is reacted with acetone.The compound of formula (I) has antibacterial activity in a living organism when used for the treatment of mammals, and this activity can be demonstrated using standard methods using for penicillin compounds, for example, by administering to mice in which acute infection was caused by intra-abdominal inoculation of a standardized culture of pathogenic bacteria. The severity of the infection was measured on a scale such that bacteria were administered to the mice at the end of the test LD compounds were evaluated by counting the number of smaller survivors who were injected with bacteria and who also obtained the compound of formula (I). The activity of the antibacterial compound of formula (I) makes it suitable for eliminating bacterial infections in mammals, including humans, both by oral and parenteral administration. For comparison, a known antibacterial compound of formula (II) was used. The compound of formula (I) decomposes into ampicillin and penicillanic acid 1,1-dioxide after it is introduced into the mammalian body both orally and parenterally. Penicillanic acid 1,1-Dioxide further acts as an inhibitor of B-lactamase and increases the antibacterial efficacy of ampicillin, for example, against strains of the species Staphylococcus aureus, Eschirichia coli producing penicillin IL. Alternatively, a shnally inhibitory concentration of the mixture consisting of 1: 1 ampicillin and 1,1-dioxide penicillanic acid can be measured. This minimum inhibitory concentration can be measured using a technique that uses a transparent heart infusion of agar and a graft device. Tubes grown overnight were diluted 100-fold for use as a standard graft material (20,000-10,000 cells in approximately 0.002 MP were placed on the surface of an agar / 20 ml transparent heart infar agar per dish). 12 2-fold dilutions of the test compound are used. The initial qi concentration of the drug being tested is 200 µg / ml. Single colonies were not counted. The plates were analyzed after 18 h at. Sensitivity (minimal inhibitory concentration) of the test organism was taken as the lowest concentration of the compound, able to ensure complete growth inhibition when evaluated by the naked eye. The proposed compound was tested to determine the serum level of the compound in experimental animals (laboratory rats). Data on serum levels in bound rats after oral administration of 20 mg / kg of live weight of 1,1-dioxide b- (2,2-dimethyl-4-phenyl-5-imidazolidinon-1-yl) penicillanoyloxymethyl penicillanate are given in the table. According to this experience, b- (2-amio-2-phenylacetamido) penicillanoploxymethyl penicillanate 1,1-dioxide. llj in the same oral dosage was used as a control sample. The level of ampicillin in the blood was determined using standard bioassays on a plate using Sarcina lutea 07A001 on agar. Pasturella 59 VOY on agar was used to determine the 1,1-dioxide of penicillanic acid. An approximately 50% improvement in half-life was achieved for compound (I) compared with compound (II). In the case when the proposed antibacterial compound is used for treating mammals, especially humans, this compound can be administered either in its pure form and can be mixed with other antibiotics and / or pharmaceutically acceptable carriers or diluents. These carriers or diluents are selected depending on the manner in which the drug is intended to be administered. In cases where oral administration is preferred, the antibacterial compound may be used in the form of tablets, capsules, pills, powder, lozenges, syrups, elixirs, aqueous solutions and suspensions in accordance with standard terraretic practice. The ratio between the amounts of active ingredient and carrier will naturally depend on the chemical nature, solubility and stability of the active ingredient, as well as on the intended dosage. In the case of tablets, carriers may be lactose, sodium citrate and phosphoric acid salts. Various disintegrants, such as starch, or lubricating agents, such as magnesium stearate, sodium lauryl sulfate and talc, are commonly used in tablets. For oral administration in capsule form, suitable diluents are lactose and high molecular weight polyethylene glycols, the molecular weight of which is 24 thousand. In cases where it is necessary to use aqueous suspensions for oral administration, the active ingredient is mixed with emulsifying and suspending agents. If necessary, flavoring and flavoring agents can be added. The daily dose of the antibiotic will vary depending on the age, weight, and individual response of the patient, and will also depend on the nature and severity of the disease. Typically, the proposed compounds can be used orally or parenterally at dosages in the range of about 5,100 mg / kg of live weight per day, usually in divided doses. In some cases, it may be necessary to go beyond this range. Example. Preparation of (2,2-dimethyl-4-phenyl-5-imidazolidinon-1-yl) penicilanyloxymethyl penicillanate 1,1-dioxide l. b- (2-Amino-2-phenylacetamido) penicillanoyloxymethyl penicillanate 1,1-dioxide p (594 kg, 1 mol) is stirred in 30 ml of acetone at room temperature. After 65 hours, the resulting reaction mixture was evaporated to give a dry product in vacuo, yielding an almost quantitative yield of the product, indicated in the title. M.p. 115-125 C NMR spectrum (SDSC), parts per million: 1.3-1.7 (18H, three pairs of heme-dimethyl groups), 3.4 (2H, C-6 CH2), 4.24, 7 SbN , C-3, C-7, C-3, C-6 and CH), 5.5 (1H, side chain CH), 5.8 (2H, -OCH20-) and 2.3 (5H aromatic).
    权利要求:
    Claims (1)
    [1]
    METHOD FOR PRODUCING THE COMPLEX BI.S.-ETHER OF METHANEDIOL WITH PENICYLANIC ACID DERIVATIVE AND PENICILLANIC ACID 1,1-DIOXIDE OF FORMULA sn 3 sn 3 s — o
    II I characterized in that, 'in the I) form is reacted with acetone.
    >
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    同族专利:
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    引用文献:
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US24650381A| true| 1981-03-23|1981-03-23|
    US06/246,504|US4321196A|1981-03-23|1981-03-23|Bis-esters of methanediol with acetonides of ampicillin or amoxicillin and penicillanic acid 1,1-dioxide|
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