- 2-CYANOPYRROLDINES, -PIPERIDINES OR -DAZEPINES AS HYPERGLYCEMIC AGENTS
-
Nitrogen containing compounds of Formula (I), pharmaceutical compositions comprising these compounds and their use in treating hypoglycaemia is disclosed.
- -
-
Page/Page column 50-51
(2021/08/27)
-
- CRYSTALLINE FORM OF AN AVIBACTAM DERIVATIVE
-
A crystalline form of an avibactam derivative (1), i.e. crystalline ethyl 3-(((((1R,2S,5R)-2-carbamoyl-7-oxo-l,6-diazabicyclo[3.2.1]octan-6-yl)oxy)sulfonyl)oxy)-2,2-dimethylpropanoate anhydrate (I), pharmaceutical compositions thereof, and the use of the crystalline avibactam derivative for treating bacterial infections are provided.
- -
-
Paragraph 257-258
(2020/09/27)
-
- Avibactam intermediate, and preparation method and application of avibactam intermediate
-
The invention discloses an avibactam intermediate, and a preparation method of the avibactam intermediate. The preparation method comprises the steps of allowing a compound II to react with a sulfonation reagent in the presence of an alkaline agent and then react with the alkaline agent to form the avibactam intermediate, wherein the alkaline agent is trialkylamine, pyridine, alkylpyridine, N-alkylpiperidine, dialkyl phenylamine or dialkyl benzylamine; alkyl in trialkyl amine is C5-8 alkyl; alkyl in alkyl pyridine in C1-4 alkyl; alkyl in N-alkylpiperidine is C1-4 alkyl; alkyl in dialkyl phenylamine is C1-4 alkyl; and alkyl in dialkyl benzylamine is C1-4 alkyl. Compared with the traditional method, the method adopts the alkaline agent with appropriate alkalinity to substitute the traditional alkaline agent; the alkaline agent can react with the compound II in a step directly with the sulfonation reagent; the post-treatment is simple; and the method is more suitable for industrial mass production.
- -
-
Paragraph 0037; 0045-0046; 0048-0049; 0051-0052; 0053-0058
(2019/09/17)
-
- Orally Absorbed Derivatives of the β-Lactamase Inhibitor Avibactam. Design of Novel Prodrugs of Sulfate Containing Drugs
-
Only one FDA-approved β-lactamase inhibitor has ever been orally available: clavulanic acid, approved in 1984. Avibactam, approved by FDA in 2015, is the first of a new class of BLIs called diazabicyclooctanes, or "DBOs". This class has much broader coverage than clavulanic acid but can only be administered by intravenous injection. Herein, we describe the synthesis and testing of the first approved BLI to be rendered orally bioavailable since clavulanic acid (1984).
- Gordon, Eric M.,Duncton, Matthew A. J.,Gallop, Mark A.
-
supporting information
p. 10340 - 10344
(2018/11/23)
-
- Beta-lactamase inhibitors and uses thereof
-
β-Lactamase inhibiting compounds, therapeutic methods of using the β-lactamase inhibiting compounds, particularly in combination with β-lactam antibiotics and pharmaceutical compositions thereof are disclosed. The β-lactamase inhibiting compounds are suitable for oral administration.
- -
-
Page/Page column 82; 83
(2018/10/24)
-
- Synthetic method for avibactam sodium salt
-
The invention discloses a synthetic method for avibactam sodium salt. The method comprises the following steps: taking (2S, 5R)-5-[(benzyl oxyl) amino] piperidine-2-formamide as a starting material; constructing a urea ring by carbonyl diimidazole under the effect of dimethyldichlorosilance to obtain (2S, 5R)-6-(benzyl oxyl)-7-oxo-1,6-diazabicyclo [3.2.1] octane-2-formamide; then carrying out hydrogenation to remove benzyl; carrying out sulfonation reaction on the compound and a sulfonated reagent; synthesizing into a quaternary ammonium salt intermediate by using quaternary ammonium salt; and finally carrying out ion exchange to obtain the avibactam sodium salt. The improved process is low in cost, simple and convenient to operate, good in product quality and suitable for industrial production. In a process of synthesizing the intermediate (2S, 5R)-6-(benzyl oxyl)-7-oxo-1,6-diazabicyclo [3.2.1] octane-2-formamide, dimethyldichlorosilance which is low in price is used, and therefore, the production cost is greatly reduced.
- -
-
Paragraph 0036; 0039
(2017/12/29)
-
- One-pot method of preparing avey batanBatan sodium (by machine translation)
-
The invention discloses a method for preparing avey batanBatan sodium pot method. The method to (2S, 5R) - 5 - [(benzyloxy) amino] piperidine - 2 - carboxylic acid ethyl ester oxalate as the starting material first with triphosgene generating compounds II, then after hydrolysis to obtain compound III ammoniation of adding ammonia water, then in hydrogenation reaction using formic acid, ammonium formate or hydrazine hydrate as hydrogen donor hydrogenation after avey batanBatan sodium and get. The method adopts the one-pot preparation avey batanBatan sodium, and the raw material is cheap, mild reaction conditions, the operation is simple, and higher safety, high yield, purity is good, is suitable for the large-scale industrial production. (by machine translation)
- -
-
-
- Diazabicyclo octanone sulfuric acid monoester synthesis method
-
The invention relates to a synthesis method of a compound diazabicyclo octanone sulfuric acid monoester for preventing and treating bacterial infection diseases. According to the synthesis method, cheap and available glutamate lactam is taken as a raw material and reacts for twelve steps, and chemical synthesis of diazabicyclo octanone sulfuric acid monoester is completed with higher total yield. According to the novel synthesis method of diazabicyclo octanone sulfuric acid monoester, the preparation method is simple and convenient, an intermediate is stable, environmental protection and economy are achieved, and the reaction is easy to control.
- -
-
-
- Method for synthesizing beta-lactamase inhibitor Avibactam
-
The invention relates to a method for synthesizing a beta-lactamase inhibitor Avibactam and belongs to the technical field of preparation of beta-lactamase inhibitors. The method disclosed by the invention comprises the following steps: (1) taking a compound 2 as a raw material, and reacting with RNH2 so as to produce a compound 3; (2) enabling the compound 3 and a biocatalyst to produce a compound 4 in an organic solvent in the presence of glucose or sucrose; (3) enabling the compound 4 to react with trifluoroacetic anhydride so as to obtain a compound 5; (4) enabling the compound 5 to react with RONH2 so as to produce a compound 6; (5) hydrolyzing the compound 6 under alkaline conditions so as to produce a compound 7; (6) enabling the compound 7 to react with triphosgene so as to produce a compound 8; (7) enabling the compound 8 to react with ammonium formate in the presence of a catalyst so as to produce a compound 9 in the organic solvent, wherein the catalyst is a Pd/C system; and (8) enabling the compound 9 to react with a sulfonating agent, thereby obtaining the product 1. The method disclosed by the invention is stable in process, high in yield, simple and safe in operation and low in production cost.
- -
-
-
- A PROCESS FOR SODIUM SALT OF (2S, 5R)-2-CARBOXAMIDO-7-OXO-6-SULFOOXY -1,6-DIAZA-BICYCLO[3.2.1]OCTANE
-
A process for preparation of a sodium salt of (2S, 5R)-2- carboxamido-7-oxo-6-sulfooxy-l,6-diaza-bicyclo[3.2.1]octane is disclosed which is comprising the amidation of a compound of Formula (II) to obtain a compound of Formula (III).
- -
-
-
- OPTICALLY-ACTIVE DIAZABICYCLOOCTANE DERIVATIVE AND METHOD FOR MANUFACTURING SAME
-
Provided are an optically active diazabicyclooctane derivative defined by formula (F) below, which is useful as a pharmaceutical intermediate for β-lactamase inhibitor, and a process for preparing the same. In formula (F) above, R1 represents CO2R, CO2M, or CONH2, wherein R represents a methyl group, a tert-butyl group, an allyl group, a benzyl group, or a 2,5-dioxopyrrolidin-1-yl group, and M represents a hydrogen atom, an inorganic cation, or an organic cation; and R2 represents a benzyl group or an allyl group.
- -
-
-
- OPTICALLY ACTIVE DIAZABICYCLOOCTANE DERIVATIVES AND PROCESS FOR PREPARING THE SAME
-
Provided are an optically active diazabicyclooctane derivative defined by formula (F) below, which is useful as a pharmaceutical intermediate for beta-lactamase inhibitor, and a process for preparing the same. In formula (F) above, R1 represents CO2R, CO2M, or CONH2, wherein R represents a methyl group, a tert-butyl group, an allyl group, a benzyl group, or a 2,5-dioxopyrrolidin-1-yl group, and M represents a hydrogen atom, an inorganic cation, or an organic cation; and R2 represents a benzyl group or an allyl group.
- -
-
-
- Heterocyclic compounds as inhibitors of beta-lactamases
-
This invention discloses and claims methods for inhibiting bacterial β-lactamases and treating bacterial infections by inhibiting bacterial β-lactamases in man or an animal comprising administering a therapeutically effective amount to said man or said animal of a compound, or pharmaceutically acceptable salt thereof, of formula (I) either alone or in combination with a β-lactamine antibiotic wherein said combination can be administered separately, together or spaced out over time. Pharmaceutical compositions comprising a compound of formula (I), or a combination of a compound of formula (I) and a therapeutically effective amount of a β-lactamine antibiotic, and a pharmaceutically acceptable carrier are also disclosed and claimed. 1
- -
-
-
- Azabicyclic compounds, preparation thereof and use as medicines, in particular as antibacterial agents
-
The invention relates to new heterocyclic compounds of general formula (I), and their salts with a base or an acid: The invention also relates to a process for the preparation of these compounds as well as their use as medicaments, in particular as anti-bacterial agents.
- -
-
Page/Page column 35
(2010/11/30)
-