- Preparation method of avibactam sodium
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The invention discloses a synthesis method of avibactam sodium. (2S,5R)-benzyloxyamino piperidine-2-ethyl formate oxalate (I) is used as an initial raw material; and the method comprises the followingsteps: reacting the raw material with a protecting group, carrying out carbonylation cyclization, carrying out hydrolysis of ester, ammoniating, sulfonating with a sulfur trioxide complex, salifyingwith an ammonium ion source, and salifying with a sodium salt to obtain avibactam sodium, and has the advantages of simple operation, easily controlled conditions, easy industrial production and wideapplication prospect.
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- Discovery of ANT3310, a Novel Broad-Spectrum Serine β-Lactamase Inhibitor of the Diazabicyclooctane Class, Which Strongly Potentiates Meropenem Activity against Carbapenem-Resistant Enterobacterales and Acinetobacter baumannii
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The diazabicyclooctanes (DBOs) are a class of serine β-lactamase (SBL) inhibitors that use a strained urea moiety as the warhead to react with the active serine residue in the active site of SBLs. The first in-class drug, avibactam, as well as several other recently approved DBOs (e.g., relebactam) or those in clinical development (e.g., nacubactam and zidebactam) potentiate activity of β-lactam antibiotics, to various extents, against carbapenem-resistant Enterobacterales (CRE) carrying class A, C, and D SBLs; however, none of these are able to rescue the activity of β-lactam antibiotics against carbapenem-resistant Acinetobacter baumannii (CRAB), a WHO "critical priority pathogen"producing class D OXA-type SBLs. Herein, we describe the chemical optimization and resulting structure-activity relationship, leading to the discovery of a novel DBO, ANT3310, which uniquely has a fluorine atom replacing the carboxamide and stands apart from the current DBOs in restoring carbapenem activity against OXA-CRAB as well as SBL-carrying CRE pathogens.
- Davies, David T.,Leiris, Simon,Zalacain, Magdalena,Sprynski, Nicolas,Castandet, Jér?me,Bousquet, Justine,Lozano, Clarisse,Llanos, Agustina,Alibaud, Laethitia,Vasa, Srinivas,Pattipati, Ramesh,Valige, Ravindar,Kummari, Bhaskar,Pothukanuri, Srinivasu,De Piano, Cyntia,Morrissey, Ian,Holden, Kirsty,Warn, Peter,Marcoccia, Francesca,Benvenuti, Manuela,Pozzi, Cecilia,Tassone, Giusy,Mangani, Stefano,Docquier, Jean-Denis,Pallin, David,Elliot, Richard,Lemonnier, Marc,Everett, Martin
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p. 15802 - 15820
(2021/01/09)
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- B-LACTAMASE INHIBITOR AND APPLICATION THEREOF
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The present invention relates to a compound of Formula (I)-(IV) useful as β-lactamase inhibitor, a pharmaceutically acceptable salt, ester, solvate or stereoisomer thereof, wherein R1, R2, M and ring A have definitions as those in the specification. The present invention further relates to methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and uses of these compounds. For example, the compounds of the present invention can be used as β-lactamase inhibitors, for treatment and/or prophylaxis of diseases caused by bacterial infections, solving drug-resistance problems caused by β-lactamases, especially bacterial drug-resistant diseases caused by type B metallo-β-lactamases.
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Paragraph 0103; 0104
(2018/03/07)
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- Production method for diazabicyclooctane derivative and intermediary body thereof
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The present invention provides a production method for a diazabicyclooctane derivative expressed by formula (IV), and an intermediary body thereof (in the formula: P is an acid-removable NH protective group; R1 represents a 2, 5-dioxopyrrolidine-1-yl, a 1, 3-dioxo-3a, a 4, 7, 7a-tetrahydro-1H-isoindole-2(3H)-yl, a 1, 3-dioxohexahydro-1H-isoindole-2(3H)-yl, or a 3, 5-dioxo-4-azatricyclo[5.2.1.02, 6]deca-8-en-4-yl; R2 represents hydrogen, C1CO-, or C13COCO-, R3 represents a C1-6 alkyl or a heterocyclyl, or joins with a bonded -O-NH- to form a 3-7 member heterocyclyl ring; and OBn represents a benzyloxy).
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- CRYSTALLINE FORMS OF DIAZABICYCLOOCTANE DERIVATIVE AND PRODUCTION PROCESS THEREOF
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A crystalline form of a diazabicyclooctane derivative represented by the following Formula (VII), and processes for producing the same:
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- CRYSTAL OF DIAZABICYCLEOCTANE DERIVATE AND METHOD FOR PRODUCING THE SAME
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The present invention provides a crystal of diazabicycleoctane derivate represented by the following formula (VII), especially formula (VII-1), and a method for producing the same.
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- NOVEL -LACTAMASE INHIBITOR AND METHOD FOR PRODUCING SAME
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The currently available β-lactamase inhibitors are insufficient to inhibit the incessantly increasing β-lactamase, and novel β-lactamase inhibitors has been required today for the difficult treatment for bacterial infectious diseases caused by resistant bacteria which produce class C β-lactamase, extended-spectrum β-lactamase (ESBL) belonging to class A and D, or class A KPC-2 decomposing even carbapenem as a last resort for β-lactam antibiotic. A compound represented by the the formula (I), preparation process of the same, β-lactamase inhibitors and method for treating bacterial infectious diseases are provided.
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- SODIUM SALT OF (2S, 5R)-6-BENZYLOXY-7-OXO-1,6-DIAZA-BICYCLO [3.2.1 ] OCTANE-2-CARBOXYLIC ACID AND ITS PREPARATION
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Sodium salt of (2S, 5R)-6-benzyloxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2- carboxylic acid and a process for its preparation is disclosed.
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Page/Page column 6; 10; 11
(2014/09/29)
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- CRYSTALLINE FORM OF A BETA-LACTAMASE INHIBITOR
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This disclosure provides compositions containing solid forms of sodium (2S,5R)-2-(1,3,4-oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate, and methods of manufacturing and using these compositions.
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- OPTICALLY-ACTIVE DIAZABICYCLOOCTANE DERIVATIVE AND METHOD FOR MANUFACTURING SAME
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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.
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- 1,2,4-OXADIAZOLE AND 1,2,4-THIADIAZOLE BETA-LACTAMASE INHIBITORS
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β-Lactamase inhibitor compounds (BLIs) are disclosed, including compounds that have activity against class A, class C or class D β-lactamases. Methods of manufacturing the BLIs, and uses of the compounds in the preparation of pharmaceutical compositions and antibacterial applications are also disclosed.
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- BETA-LACTAMASE INHIBITORS
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Aryl substituted diazabicyclooctanes (DBO) compounds that inhibit β-lactamases of class A, class C or class D and potentiate β-lactam antibiotics are disclosed. In particular, this disclosure provides DBO compounds that, when used in the disclosed Synergy MIC Assay with a β-lactam antibiotic at a fixed concentration have an MIC of 8 μg/mL or less against one or more isogenic β-lactamase expressing bacterial strains.
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- 1,3,4-OXADIAZOLE AND 1,3,4-THIADIAZOLE BETA-LACTAMASE INHIBITORS
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β-Lactamase inhibitor compounds (BLIs) are disclosed, including compounds that have activity against class A, class C or class D β-lactamases. Methods of manufacturing the BLIs, and uses of the compounds in the preparation of pharmaceutical compositions and antibacterial applications are also disclosed.
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- OPTICALLY ACTIVE DIAZABICYCLOOCTANE DERIVATIVES AND PROCESS FOR PREPARING THE SAME
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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.
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- POLYMORPHIC AND PSEUDOPOLYMORPHIC FORMS OF A PHARMACEUTICAL COMPOUND
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The invention relates to the sodium salt of (1R,2S,5R)-7-oxo-6-sulfooxy-1,6- diazabicyclo[3.2.1]octane-2-carboxamide in hydrated or anhydrous crystallized enantiomeric form and in particular in the novel crystallized polymorphic and pseudopolymorphic forms "A", "B", "D" and "E" defined in the application, as well as the method of preparation. The compound of the invention can be used as a medicament, in particular a beta-lactamase inhibitor.
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Page/Page column 39; 40
(2011/04/26)
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- Heterocyclic compounds as inhibitors of beta-lactamases
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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
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