中科微点-全球专利检索

  1. Login
  2. Sign Up

Search Results

77 records (took 0.014 seconds)

    Alkenyl and alkinylureido cephalosporins
    11.
    发明授权
    Alkenyl and alkinylureido cephalosporins 失效
    烯基和炔基脲基头孢菌素

    公开(公告)号：US4028354A

    公开(公告)日：1977-06-07

    申请号：US664467

    申请日：1976-03-08

    Applicant: Hermann Breuer ,  Uwe D. Treuner

    Inventor： Hermann Breuer ,  Uwe D. Treuner

    IPC: C07D501/36

    CPC classification number: C07D501/36

    Abstract: Alkenyl and alkinylureido cephalosporins of the formula ##STR1## wherein R is hydrogen, lower alkyl, phenyl-lower alkyl, diphenyl-lower alkyl, tri(lower alkyl)silyl, trihaloethyl, a salt forming ion, or the group ##STR2## R.sub.1 is hydrogen or methoxy; R.sub.2 is lower alkenyl or lower alkinyl, R.sub.3 is hydrogen or lower alkyl; R.sub.4 is hydrogen, lower alkyl, cycloalkyl, cycloalkenyl, cycloalkadienyl, phenyl, phenyl-lower alkyl, substituted phenyl, substituted phenyl-lower alkyl, or certain heterocyclic groups; R.sub.5 is hydrogen or lower alkyl; R.sub.6 is lower alkyl; and X is hydrogen, lower alkanoyloxy, ##STR3## or certain heterothio groups; are disclosed. These compounds are useful as antibacterial agents.

    Abstract translation: 其中R是氢，低级烷基，苯基 - 低级烷基，二苯基 - 低级烷基，三（低级烷基）甲硅烷基，三卤代乙基，成盐离子或基团R1的烯基和炔基脲基头孢菌素 氢或甲氧基; R2是低级烯基或低级炔基，R3是氢或低级烷基; R4是氢，低级烷基，环烷基，环烯基，环链二烯基，苯基，苯基 - 低级烷基，取代的苯基，取代的苯基 - 低级烷基或某些杂环基; R5是氢或低级烷基; R6是低级烷基; X是氢，低级烷酰氧基，或者某些杂硫基; 被披露。 这些化合物可用作抗菌剂。

    3-Triazolylthio derivatives of ureido cephalosporins
    12.
    发明授权
    3-Triazolylthio derivatives of ureido cephalosporins 失效
    脲基头孢菌素的3-三唑基硫代衍生物

    公开(公告)号：US3996217A

    公开(公告)日：1976-12-07

    申请号：US611040

    申请日：1975-09-08

    Applicant: Hermann Breuer ,  Uwe D. Treuner

    Inventor： Hermann Breuer ,  Uwe D. Treuner

    IPC: C07D501/28 ,  A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D333/24 ,  C07D501/32 ,  C07D501/36 ,  C07D501/57 ,  C07D501/24

    CPC classification number: C07D333/24

    Abstract: Ureido cephalosporin derivatives of the formula ##STR1## wherein R is hydrogen, lower alkyl, phenyl-lower alkyl, diphenyllower alkyl, tri(lower alkyl)silyl, trihaloethyl, a salt forming ion, or the group ##STR2## R.sub.1 is hydrogen, lower alkyl, cycloalkyl, cycloalkenyl, cycloalkadienyl, phenyl, phenyl-lower alkyl, substituted phenyl or phenyl-lower alkyl, or certain heterocyclic groups; R.sub.2 is hydrogen or lower alkyl; R.sub.3 is hydrogen or methoxy; R.sub.4 is triazolyl or substituted triazolyl; R.sub.5 is hydrogen or lower alkyl; R.sub.6 is lower alkyl, phenyl, or phenyl-lower alkyl; are disclosed. These compounds are useful as antibacterial agents.

    Abstract translation: 其中R为氢，低级烷基，苯基 - 低级烷基，二苯基低级烷基，三（低级烷基）甲硅烷基，三卤代乙基，成盐离子或基团R 1的氢原子，头孢菌素衍生物为下式 烷基，环烷基，环烯基，环烷二烯基，苯基，苯基 - 低级烷基，取代的苯基或苯基 - 低级烷基或某些杂环基; R2是氢或低级烷基; R3是氢或甲氧基; R4是三唑基或取代的三唑基; R5是氢或低级烷基; R6是低级烷基，苯基或苯基 - 低级烷基; 被披露。 这些化合物可用作抗菌剂。

    [(Oxyalkyl)thioacetyl]cephalosporin derivatives
    13.
    发明授权
    [(Oxyalkyl)thioacetyl]cephalosporin derivatives 失效
    {8（氧烷基）硫代乙酰基{9头孢菌素衍生物

    公开(公告)号：US3991051A

    公开(公告)日：1976-11-09

    申请号：US573676

    申请日：1975-05-01

    Applicant: Hermann Breuer ,  Uwe D. Treuner

    Inventor： Hermann Breuer ,  Uwe D. Treuner

    IPC: C07D501/20 ,  C07D501/28 ,  C07D501/32

    CPC classification number: C07C323/00

    Abstract: [(Oxyalkyl)thioacetyl] cephalosporin derivatives having the formula ##EQU1## wherein R is hydrogen, lower alkyl, phenyl-lower alkyl, tri(lower alkyl)silyl, a salt forming ion, or the group ##EQU2## R.sub.1 is hydrogen, lower alkyl, phenyl, thienyl or furyl; R.sub.2 and R.sub.6 each is hydrogen or lower alkyl; R.sub.3 and R.sub.5 each is lower alkyl, phenyl or phenyl-lower alkyl; and R.sub.4 is hydrogen, hydroxy, lower alkanoyloxy, lower alkoxy or lower alkylthio; are useful as antimicrobial agents.SUMMARY OF THE INVENTIONThis invention relates to new [(oxyalkyl)thioacetyl]cephalosporin derivatives having the formula ##STR1##R represents hydrogen, lower alkyl, phenyl-lower alkyl, tri(lower alkyl)silyl, a salt forming ion or the group ##STR2## R.sub.1 represents hydrogen, lower alkyl, phenyl, thienyl or furyl; R.sub.2 and R.sub.6 each represents hydrogen or lower alkyl; R.sub.3 and R.sub.5 each represents lower alkyl, phenyl or phenyl-lower alkyl; and R.sub.4 represents hydrogen, hydroxy, lower alkanoyloxy, lower alkoxy or lower alkylthio.The especially preferred members within each group are as follows: R is hydrogen, alkali metal, diphenylmethyl or ##STR3## especially hydrogen, pivaloyloxy, sodium or potassium; R.sub.1 is hydrogen or phenyl; R.sub.2 is hydrogen; R.sub.3 is lower alkyl, especially methyl; R.sub.4 is hydrogen or acetoxy; and R.sub.5 is methyl or t-butyl.DETAILED DESCRIPTION OF THE INVENTIONThe various groups represented by the symbols have the meanings defined below and these definitions are retained throughout this specification.The lower alkyl groups are the straight and branched chain hydrocarbon groups in the series from methyl to heptyl, the C.sub.1 to C.sub.4 groups and especially methyl and ethyl being generally preferred. The lower alkoxy and lower alkylthio groups are of the same type and the same preferences apply.The lower alkanoyloxy groups represented by R.sub.4 include the acyl radicals of lower fatty acids containing alkyl radicals of the type described above, e.g., acetoxy, propionoxy, butyryloxy, etc., the C.sub.1 to C.sub.4 members being preferred and acetoxy being especially preferred.The phenyl-lower alkyl radicals include a phenyl ring attached to a lower alkyl group of the kind described above like benzyl and phenethyl as well as those containing two phenyl groups such as diphenylmethyl.The salt forming ions represented by R are metal ions, e.g., alkali metal ions such as sodium or potassium, alkaline earth metal ions such as calcium or magnesium or an amine salt ion, e.g., a (lower alkyl)amine like methylamine or triethylamine.The new [(oxyalkyl)thioacetyl)cephalosporin derivatives of this invention are produced by reacting a 7-aminocephalosporanic acid compound, e.g., 7-aminocephalosporanic acid (7-ACA), 7-amino-3-desacetoxycephalosporanic acid (7-ADCA) and other derivatives, having the formula ##STR4## or derivatives thereof with an [(oxyalkyl)thio]acetic acid of the formula ##STR5## or an acid halide, anhydride including mixed anhydrides, activated esters or the like.The derivatives of II referred to include, for example, the triethylamine derivative, benzhydryl ester or the like. The acid halide of III is preferably the chloride. Coupling agents like dicyclohexylcarbodiimide or the like can also be used.A preferred method is the reaction between the 7-aminocephalosporanic acid compound and the [(oxyalkyl)-thio]acetic acid, for example, by dissolving or suspending the latter in an inert organic solvent such as chloroform, tetrahydrofuran, methylene chloride, dioxane, benzene or the like, and adding, at a reduced temperature of about 0.degree. to -20.degree. C about an equimolar amount of the 7-ACA or 7-ADCA compound, preferably in the form of its diphenylmethyl ester, in the presence of an activating compound such as dicyclohexylcarbodiimide. The product of the reaction is then isolated by conventional procedures, e.g., by filtration and concentration or evaporation of the solvent. The diphenylmethyl ester is converted to the free acid, e.g., with trifluoroacetic acid and anisole. Any of the salts can then be produced by conventional treatment, e.g., with potassium ethyl hexanoate, sodium bicarbonate or the like.Another preferred method involves the reaction of a 7-aminocephalosporanic acid compound with the acid halide of the [(oxyalkyl)thio]acetic acid in aqueous alkaline medium.When R is the acyloxymethyl group ##STR6## this group may be introduced into the 7-aminocephalosporanic acid moiety prior to the reaction with the [(oxyalkyl)thio]-acetic acid or derivative by treatment with one to two moles of a halomethyl ester of the formula ##STR7## wherein hal is halogen, preferably chlorine or bromine, in an inert organic solvent such as dimethylformamide, acetone, dioxane, benzene or the like, at about ambient temperature or below.The [(oxyalkyl)thio]acetic acid of formula III is produced by reacting a mercaptoacetic acid of the formula ##STR8## with a halogenated compound of the formula ##STR9## in the presence of a base like triethylamine in a solvent like tetrahydrofuran and then hydrolyzing the ester formed in the process.Alternatively, when the acid halide is used to react with the 7-aminocephalosporanic acid compound, an alkoxide R.sub.3 -OMe (wherein Me is a metal like sodium or potassium) is made to react with a haloester of the formula ##STR10## to obtain the intermediate of the formula ##STR11##Treatment with a base, e.g., an alkali metal hydroxide like potassium hydroxide, converts the ester to a salt which is then converted to the acid chloride with a halogenating agent like oxalyl chloride.Further process details are provided in the illustrative examples.Certain of the compounds of this invention may exist in different optically active forms. The various stereoisomeric forms as well as the racemic mixtures are within the scope of the invention.The compounds of this invention have a broad spectrum of antibacterial activity against both gram positive and gram negative organisms such as Staphylococcus aureus, Salmonella schottmuelleri, Pseudomonas aeruginosa, Proteus vulgaris, Escherichia coli and Streptococcus pyrogenes. They can be used as antibacterial agents to combat infections due to organisms such as those named above, and in general may be utilized in a manner similar to cephradine and other cephalosporins. For example, a compound of formula I or a physiologically acceptable salt thereof can be used in various animal species in an amount of about 1 to 150 mg/kg, daily, orally or parenterally, in single or two to four divided doses to treat infections of bacterial origin, e.g., 7.0 mg/kg is used in mice.Up to about 600 mg. of a compound of formula I or a physiologically acceptable salt thereof is incorporated in an oral dosage form such as tablets, capsules or elixirs or in an injectable form in a sterile aqueous vehicle prepared according to conventional pharmaceutical practice.

    Abstract translation: 具有下式的[（氧代烷基）硫代乙酰基]头孢菌素衍生物：R 2 R 3 S || R 3 -O-CH-S-CH-CO-NH-CH-CHCH 2 || C-NC-CH 2 -R 4平行角OC | C-OR 其中R是氢，低级烷基，苯基 - 低级烷基，三（低级烷基）甲硅烷基，成盐离子或基团R6O |平行-CH-OC-R5; R 1是氢，低级烷基，苯基，噻吩基或呋喃基; R2和R6各自为氢或低级烷基; R3和R5各自为低级烷基，苯基或苯基 - 低级烷基; 和R4是氢，羟基，低级烷酰氧基，低级烷氧基或低级烷硫基; 作为抗微生物剂是有用的。

    Hydrazide containing derivatives of 2-amino-4-thiazole-acetic acid
    17.
    发明授权
    Hydrazide containing derivatives of 2-amino-4-thiazole-acetic acid 失效

    公开(公告)号：US4680409A

    公开(公告)日：1987-07-14

    申请号：US812658

    申请日：1985-12-23

    Applicant: Uwe D. Treuner

    Inventor： Uwe D. Treuner

    IPC: C07D277/20 ,  C07D277/40 ,  C07D417/12 ,  C07D417/14

    CPC classification number: C07D277/587 ,  C07D417/12 ,  C07D417/14

    Abstract: Compounds having the formula ##STR1## wherein R.sub.1 and R.sub.2 are each independently hydrogen or alkyl of 1 to 4 carbon atoms, or R.sub.1 and R.sub.2 together with the carbon atom to which they are attached form a cycloalkyl ring;R.sub.3 is hydrogen or alkyl;R.sub.4 is hydrogen or alkyl, and R.sub.5 is hydrogen, alkyl, phenyl, substituted phenyl, a 4,5,6 or 7-membered heterocycle, phenylalkyl, (substituted phenyl)alkyl, (4,5,6 or 7-membered heterocycle)alkyl, ##STR2## or together R.sub.4 and R.sub.5 are .dbd.CH--Y.sub.7 ; wherein Y.sub.1 is hydrogen, alkyl, phenyl, substituted phenyl, methylcarbonyl, trifluoromethylcarbonyl, phenylcarbonyl, (substituted phenyl)carbonyl, carboxymethyl, methylsulfonyl, phenylsulfonyl, (substituted phenyl)sulfonyl, aminocarbonyl, aminocarbonylamino, aminoethyl, hydroxy, alkoxy, amino, alkylamino, dialkylamino, phenylcarbonylamino, (substituted phenyl)carbonylamino, 1-pyrrolidinyl or 1-piperidinyl; Y.sub.2 is hydrogen, alkyl, phenyl, substituted phenyl, a 4,5,6 or 7-membered heterocycle, alkoxy, formyl, carbonyl, aminocarbonyl, aminothiocarbonyl, methylaminocarbonyl, methylaminothiocarbonyl, trifluoromethyl, phenylmethyl, (substituted phenyl)methyl, phenyloxymethyl, (substituted phenyl)oxymethyl, cyanomethyl, hydroxymethyl, alkoxymethyl, aminomethyl, methylcarbonylaminomethyl, aminocarbonylaminomethyl, methylsulfonylaminomethyl, carboxymethyl, aminocarbonylmethyl, alkoxycarbonylmethyl, (4,5,6 or 7-membered heterocycle)-alkyl, hydroxyaminocarbonylmethyl, or azidomethyl; Y.sub.3 is amino, alkyl, alkylthio, carboxythio, alkoxycarbonylthio or aminocarbonylthio; Y.sub.4 is alkyl, amino, hydroxyamino, alkoxyamino, methylcarbonylamino, or phenylcarbonylamino; Y.sub.5 is hydrogen or alkyl; Y.sub.6 is hydrogen, alkyl, carboxymethyl, or aminocarbonylmethyl; and Y.sub.7 is phenyl or substituted phenyl;are useful chemical intermediates for the preparation of .beta.-lactam antibiotics.

    Iminothiazolyl ureido cephalosporins
    18.
    发明授权
    Iminothiazolyl ureido cephalosporins 失效
    亚氨基噻唑基脲基头孢菌素

    公开(公告)号：US4461767A

    公开(公告)日：1984-07-24

    申请号：US46068

    申请日：1979-06-06

    Applicant: Hermann Breuer ,  Uwe D. Treuner ,  Theodor Denzel

    Inventor： Hermann Breuer ,  Uwe D. Treuner ,  Theodor Denzel

    IPC: C07D277/20 ,  C07D501/36 ,  A61K31/545 ,  C07D501/56

    CPC classification number: C07D277/20

    Abstract: Cephalosporins of the formula ##STR1## wherein R is hydrogen, sodium, potassium or certain ester groups; R.sub.1 is in the .alpha.-configuration and is hydrogen or methoxy; R.sub.2 is hydrogen, ##STR2## R.sub.4 is hydrogen or lower alkyl; R.sub.5 is hydrogen, lower alkyl, ##STR3## or --(CH.sub.2).sub.n --N--(lower alkyl).sub.2 ; R.sub.6 is hydrogen, sodium, or potassium; n is an integer from 1 to 4; are disclosed. These compounds are useful as anti-bacterial agents.

    Abstract translation: 其中R为氢，钠，钾或某些酯基团的式“IMAGE”的头孢菌素; R1为α构型，为氢或甲氧基; R2是氢，R4是氢或低级烷基; R4是氢或低级烷基; R5是氢，低级烷基，或者 - （CH2）n-N-（低级烷基）2; R6是氢，钠或钾; n是1至4的整数; 被披露。 这些化合物可用作抗细菌剂。

    Cephalosporins having an imino substituted piperazindioncarbonylamino acyl sidechain
    19.
    发明授权
    Cephalosporins having an imino substituted piperazindioncarbonylamino acyl sidechain 失效
    具有亚氨基取代的哌嗪基羰基氨基酰基侧链的头孢菌素

    公开(公告)号：US4386199A

    公开(公告)日：1983-05-31

    申请号：US259876

    申请日：1981-05-04

    Applicant: Uwe D. Treuner ,  Hermann Breuer

    Inventor： Uwe D. Treuner ,  Hermann Breuer

    IPC: C07D241/08 ,  C07D501/36 ,  C07D501/56

    CPC classification number: C07C251/72 ,  C07D241/08

    Abstract: Cephalosporins of the formula ##STR1## wherein R is hydrogen, sodium, potassium, or certain ester groups; R.sub.1 is in the .alpha.-configuration and is hydrogen or methoxy; R.sub.2 is hydrogen, lower alkyl, cycloalkyl, cycloalkenyl, cycloalkadienyl, substituted or unsubstituted phenyl, benzyl, phenethyl, thienyl, furyl, or pyridyl, or 2-amino-4-thiazolyl; R.sub.3 is lower alkyl or substituted or unsubstituted phenyl, benzyl, phenethyl, thienyl, or furyl; R.sub.4 is hydrogen or lower alkyl; and X is hydrogen, ##STR2## --O--lower alkyl, or certain substituted or unsubstituted heterothio groups; are disclosed. These compounds possess useful antibacterial activity.

    Abstract translation: 其中R是氢，钠，钾或某些酯基团的式“IMAGE”的头孢菌素; R1为α构型，为氢或甲氧基; R2是氢，低级烷基，环烷基，环烯基，环烷二烯基，取代或未取代的苯基，苄基，苯乙基，噻吩基，呋喃基或吡啶基，或2-氨基-4-噻唑基; R3是低级烷基或取代或未取代的苯基，苄基，苯乙基，噻吩基或呋喃基; R4是氢或低级烷基; 和X是氢，或者某些取代或未取代的杂硫基; 被披露。 这些化合物具有有效的抗菌活性。

Patent Agency Ranking