134 results about "Cephem" patented technology

A novel cephem compound of the formula:wherein R1 is a phosphono group or a group convertible to a phosphono group; R2 is a hydrogen atom or a group having a linkage through a carbon atom; each of Q and X is a nitrogen atom or CH; Y is S, O or CH2; n is 0 or 1; one of R3 and R4 is a pyridinium group which may be substituted and the other is a hydrogen atom or hydrocarbon group which may be substituted, or R3 and R4 taken together may form a quaternalized nitrogen-containing heterocyclic ring which may be substituted, or its ester or its salt, which has a superior anti-bacterial activity, stability, absorbability, etc., a production thereof and a pharmaceutical composition containing it, is provided.

The present invention provides new thioester derivatives of 4-halogeno-2-methoxyimino-3-oxo-butyric acid of the general formula (I), also, the invention provides a method by which the said thioester derivatives can be prepared by reacting 4-halogeno-2-methoxyimino-3-oxo-butyric acid of the general formula (II) with 2-mercapto-5-substituted-1,3,4-oxadiazoles of the general formula (III) in a solvent, in the presence of DMF/POCl3 and in presence of an organic base and if desired the so obtained thioester derivatives so obtained are reacted with 7-amino-cephem carboxylic acids of the general formula (V) to produce condensed products which are insitu reacted with thiourea to get cephalosporin antibiotic compounds having the general formula (VI).

The present invention provides Cephem compounds which have a wide antimicrobial spectrum and have potent antimicrobial activity against beta-lactamase producing Gram negative bacteria as follows:

A compound of the formula:

wherein,

• • X is N, CH or C—Cl;
  • T is S or the like;
  • A and G are lower alkylene or the like;
  • B is a single bond or the like;
  • D is a single bond, —NR⁷—, —CO—, —CO—NR⁷—, —NR⁷—CO—, —NR⁷—CO—NR⁷—, or the like;
  • E is optionally substituted lower alkylene;
  • F is a single bond or optionally substituted phenylene;
  • R³, R⁴, R⁵ and R⁶ each is independently hydrogen, halogene, nitrile, or the like;

or an ester, a compound protected at the amino on the ring in the 7-side chain, a pharmaceutically acceptable salt, or a solvate thereof.

A process for the preparation of cefdinir of the formula (I) the said process comprising the steps of: i) condensing 7-amino-3-cephem-4-carboxylic acid of the formula (XII) wherein R1 is as defined above with compound of the formula (XIII) in the presence of a tertiary amine and an organic solvent, followed by treatment with a base to produce a salt of compound formula (XIV), wherein M+ is a counter ion and ii) hydrolyzing the compound of the formula (XIV) using an acid in the presence of a solvent to produce cefdinir of formula (I).

The invention relates to a synthetic method of ceftazidime intermediate; 7-amino cephalsporanic acid is used as a raw material; a silanization reaction, an iodination reaction, and a pyridine reaction are performed; the obtained product is added with an oxidant, and hydrochloric acid or is added into a mixed solvent of an organic solvent and water to prepare a halogen acid salt of the ceftazidimeintermediate (6R, 7R)-7-amino-3-pyridine methyl-ceph-3-ene-4-carboxylic acid. The invention also provides a method for preparing ceftazidime by using the obtained intermediate halogen acid salt. The ceftazidime intermediate and ceftazidime prepared by the methods have high yield, and low production cost; the operation is simple; the discharge of three wastes is less; treatment and recovery are easy, and the methods are applicable to industrial production.

The present invention provides a reagent composition for detecting β-lactamase including as a β-lactamase detection substrate 3-[2,4-dinitrostyryl]-7-(2-thienylacetamido]-3-cephem-4-carboxylic acid, or 7-[2-(2-aminothiazol-4-yl)-2-(1-carboxy-1-methylethoxy-imino)acetamido]-3-(2,4-dinitrostyryl)-3-cephem-4-carboxylic acid, and at least one β-lactamase inhibitor selected from the group consisting of clavulanic acid, aztreonam, ethylenediaminetetraacetic acid, and cloxacillin, which composition can detect β-lactamases rapidly and easily with high sensitivity. The present invention also provides a detection kit including the detecting reagent composition. Further, the present invention provides a β-lactamase detection method where a liquid specimen containing a target substance to be analyzed is brought into contact with the composition.

A cephem compound or pharmaceutically acceptable salt thereof represented by the formula I:

wherein R₁ and R₂ may be the same or different and each represent hydrogen atom, nitro or cyano; R₃ represents C₁-C₆ alkyl which may be substituted with carboxyl; R₄ represents hydrogen atom or amino; X represents —S— or —SO—, there being no case where both of R₁ and R₂ are simultaneously hydrogen atom.

Provided is a cephem compound which has a wide antimicrobial spectrum, and in particular exhibit potent antimicrobial activity against beta-lactamase producing Gram negative bacteria, and pharmaceutical composition comprising the same.

A Compound of the formula (I):

wherein

• • W and U are as defined in the specification;
  • R¹ is as defined in the specification;
  • R^2A and R^2B are as defined in the specification, provided that R^2A and R^2B are not taken together to form an optionally substituted oxime group when R¹ is aminothiazole or aminothiadiazole optionally protected at the amino group;
  • ring A is a benzene ring or a 6-membered aromatic heterocyclic group having 1-3 nitrogen atoms;
  • R³ is a hydrogen atom, —OCH₃ or —NH—CH(═O);
  • k is an integer from 0 to 2;
  • R⁴ is as defined in the specification; and
  • D and E are as defined in accordance with a) or b) described in the specification.

The invention provides a cefminox sodium compound of a new route, in particular a method for producing the cefminox sodium compound. The method comprises a step of generating cefminox sodium through the reaction between 7beta-bromoacetamido-7a-methoxyl-3-(1-methyl-1H-tetrazole-5-S-methyl)-3-cephem-4-carboxylic acid and D-cysteine hydrochloride, and is characterized in that: the reaction condition of the step is that the reaction is performed in aqueous solution, sodium iodide is used as a catalyst, the pH value of the reaction system is between 7.5 and 8.0, and the reaction temperature is kept at 30+/-5 DEG C. Compared with the method for producing the cefminox sodium compound in the prior art, the method of the invention for producing the cefminox sodium compound greatly improves the product yield and the purity, and solves the problem that a cefminox sodium bulk drug always has a low purity in the prior art.

The invention relates to a method for preparing ceftazidime. The synthesis method comprises the following steps: by taking 7-aminocephalosporanic acid (7-ACA) as a starting raw material, introducing a pyridine ion to 3-position methylene of 7-ACA so as to obtain 7-amino-3-(1-picolyl)-cephem acid (7-APCA) hydrochloride; then introducing a side chain with a thiazole ring on 7-position amino of the 7-APCA hydrochloride through acylation reaction; and carrying out hydrolyzing reaction, refining reaction and the like so as to obtain ceftazidime. The synthesis method for preparing the ceftazidime inthe invention is simple to operate and high in yield, and is suitable for industrial production.

A compound of the formula:

wherein

• • X is —N═, —CH═, or the like;
  • W is —CH₂— or the like;
  • U is —S— or the like;
  • R¹ and R² are each independently hydrogen, halogen, optionally substituted lower alkyl, or the like;
  • Q is a single bond or the like;
  • R³ is hydrogen or the like;
  • Ring A is a 6-membered aromatic heterocyclic group having 1-3 nitrogen atoms;
  • each R⁴ is independently hydrogen, halogen, or the like;
  • m is an integer from 0 to 2;
  • G is —C(═O)— or the like;
  • D is a single bond, —NH—, or the like; and
  • E is a cyclic quaternary ammonium group,

or an ester, a protected compound at the amino on the ring in the 7-side chain, a pharmaceutically acceptable salt, or a solvate thereof.

The present invention relates to new dosage forms of cephem compounds, useful for the treatment of bacterial infections. The dosage forms are stable, exhibit enhanced solubility, and are particularly well suited for, e.g., parenteral administration.

The present invention relates to a kind of preparation of medicinal compound, particularly a kind of preparation method of cefminox sodium. The present invention adopts a synthesis route using 7-ACA as a starting material, and the cost of raw materials is lower than that of a synthesis route using 7-MAC as a starting material. The new synthetic route uses dichloroacetyl chloride instead of bromoacetyl bromide, which reduces the toxicity and cost of raw materials. The new synthetic route increases the intermediate treatment process, reduces the amount of impurities brought by the intermediate into the next reaction, and improves the quality and stability of the finished product. The present invention overcomes the shortcomings of the synthetic route using 7-MAC as the starting material through the above improvements.

The invention relates to a ceftizoxime sosium compound of a new way. Ceftizoxime sosium is prepared by firstly reacting a cefotaxime acid with a methanoic acid to generate 2-(2-formyl aminothiazole-4-radical)-2-methoxyl imine acetic acid, then adding 7-amino-3-nor-3-cephem-4-carboxylic acid, taking triphenylphosphine oxide and triphosgene as catalysts, stirring and reacting, and regulating an acid-base pH value.

The invention discloses a new method for preparing ceftizoxime alapivoxil hydrochloride and belongs to the technical field of medicine synthesis. The method comprises the following steps: step (1), performing Boc protection on 7-amino of raw material 7-amino-3-cephem-4-carboxylic acid (7-ANCA) and then making the raw material have reaction with iodomethyl pivalate, then removing Boc protection group to obtain a midbody 7-amino-3-cephem-4-carboxylic pivaloyl oxymethyl ester (7-ANCA-POM); step (2), making N-t-butyloxycarboryl-L-alanine (Boc-L-Ala) and methoxyiminoacetic acid (ATMA) have condensation reaction to obtain a midbody 2-(2-N-t-butyloxycarboryl-amino-(S)-triacylamino-thiazole-4-yl)-2-(Z)-methoxyimino-acetic acid (Boc-L-Ala-ATMA); step (3), activating the midbody Boc-L-Ala-ATMA and making the midbody Boc-L-Ala-ATMA have condensation reaction with the midbody 7-ANCA-POM, and then removing the Boc protection group to prepare a target compound ceftizoxime alapivoxil hydrochloride (CZX-AP-HC1,I). The method adopts a collection type synthesis route, is simple and convenient to operate and mild in technical conditions, has high product quality and low cost, and avoids the problem about benzothiazole residue caused by the use of AE active ester in the present technique, so the collection type synthesis route is a good synthesis route suitable for industrial production.

A compound of the formula:

(wherein, T is S, SO or O; X is halogen, CN, carbamoyl optionally substituted with lower alkyl, lower alkyl, lower alkoxy, or lower alkylthio; A is substituted lower alkylene (wherein the substituent is optionally substituted mono lower alkyl, optionally substituted lower alkylidene, or optionally substituted lower alkylene);

[0001]
• Z⁺ is an optionally substituted, a cation and an N atom-containing heterocyclic group), ester, amino-protected compound wherein the amino bonds to a thiazole ring at the 7-position, or pharmaceutically acceptable salt or solvate thereof.

An improved process for the preparation of ceftriaxone sodium comprising the steps of:

i) reacting the 3-cephem derivative of formula (II)

 with halo acid derivative of formula (III)

 wherein X represents halogen and Y represent halogen in the presence of silylating agent and methylene chloride at −25 to 10° C., to produce (IV),

ii) quenching the reaction by pouring the reaction mixture into water or in a aqueous solution of sodium carbonate, iii) preparing sodium salt solution of (IV) by adding sodium carbonate and separating the organic layer, iv) cyclizing the sodium salt of (IV) in the aqueous solution with thiourea at a temperature in the range of 0 to 30° C., v) adjusting the pH to 1.5 to 2.5 to precipitate the ceftriaxone free acid, vi) converting the ceftriaxone free acid to sodium salt using sodium-2-ethyl hexanoate in water and vii) precipitating and isolating the ceftriaxone sodium.