1463501-48-5

Upstream product

• 1463501-45-2 (2S,5R)-1-tert-butyl 2-ethyl 5-(N-(benzyloxy)-(2-nitrophenyl)sulfonamido)piperidine-1,2-dicarboxylate 
• 1174020-25-7 (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 
• 1416134-48-9 ethyl (2S,5R)-5-[(benzyloxy)amino]piperidine-2-carboxylate oxalic acid salt 
• 1416134-73-0 (2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxylate methyl ester 
• 915976-32-8 (2S,5S)-1-tert-butyl 2-methyl 5-hydroxypiperidine-1,2-dicarboxylate 
• 915976-31-7 1-(tert-butyl) 2-methyl (S)-5-oxopiperidine-1,2-dicarboxylate 
• 108963-96-8 (S)-1-tert-butoxycarbonyl-5-methoxycarbonyl-pyrrolidin-2-one 
• 81658-26-6 tert-butyl (S)-2-(((tert-butyldimethylsilyl)oxy)methyl)-5-oxopyrrolidin-1-carboxylate 
• 541-41-3 chloroformic acid ethyl ester 
• 1416134-47-8 (2S,5R)?5?[(benzyloxy)amino]piperidine?2?carboxylate 
• 1463501-46-3 (2S,5R)-5-(benzyloxyamino)piperidin-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester 

Downstream Products

• 1471297-60-5 (2S,5R)-2-(5-amino-1,2,4-oxadiazol-3-yl)-6-(benzyloxy)-1,6-diazabicyclo[3.2.1]octan-7-one 
• 1463501-50-9 (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbaldehyde 

Relevant academic research and scientific papers

Synthesis of Avibactam Derivatives and Activity on β-Lactamases and Peptidoglycan Biosynthesis Enzymes of Mycobacteria

There is a renewed interest for β-lactams for treating infections due to Mycobacterium tuberculosis and M. abscessus because their β-lactamases are inhibited by classical (clavulanate) or new generation (avibactam) inhibitors, respectively. Here, access to an azido derivative of the diazabicyclooctane (DBO) scaffold of avibactam for functionalization by the Huisgen–Sharpless cycloaddition reaction is reported. The amoxicillin–DBO combinations were active, indicating that the triazole ring is compatible with drug penetration (minimal inhibitory concentration of 16 μg mL?1 for both species). Mechanistically, β-lactamase inhibition was not sufficient to account for the potentiation of amoxicillin by DBOs. Thus, the latter compounds were investigated as inhibitors of l,d-transpeptidases (Ldts), which are the main peptidoglycan polymerases in mycobacteria. The DBOs acted as slow-binding inhibitors of Ldts by S-carbamoylation indicating that optimization of DBOs for Ldt inhibition is an attractive strategy to obtain drugs selectively active on mycobacteria.

DIAAZABICYCLOOCTANONE DERIVATIVES AS ANTIBACTERIALS

The invention relates to a compound which is a diazabicyclooctanone of Formula (I) or a pharmaceutically acceptable salt thereof: wherein R is as defined herein. The compounds are useful in the treatment of bacterial infection, in particular they are useful in reducing bacterial resistance to antibiotics. They are also useful in the treatment of bacteria which express serine-P-lactamase enzymes, in combination with antibiotics.

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

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.

Diazabicyclooctane Functionalization for Inhibition of β-Lactamases from Enterobacteria

Second-generation β-lactamase inhibitors containing a diazabicyclooctane (DBO) scaffold restore the activity of β-lactams against pathogenic bacteria, including those producing class A, C, and D enzymes that are not susceptible to first-generation inhibitors containing a β-lactam ring. Here, we report optimization of a synthetic route to access triazole-containing DBOs and biological evaluation of a series of 17 compounds for inhibition of five β-lactamases representative of enzymes found in pathogenic Gram-negative bacteria. A strong correlation (Spearman coefficient of 0.87; p = 4.7 × 10-21) was observed between the inhibition efficacy of purified β-lactamases and the potentiation of β-lactam antibacterial activity, indicating that DBO functionalization did not impair penetration. In comparison to reference DBOs, avibactam and relebactam, our compounds displayed reduced efficacy, likely due to the absence of hydrogen bonding with a conserved asparagine residue at position 132. This was partially compensated for by additional interactions involving certain triazole substituents.

NEW BETA-LACTAMASE INHIBITORS TARGETING GRAM NEGATIVE BACTERIA

The present invention relates to a compound of the following formula (I) or a pharmaceutically acceptable salt and/or solvate thereof, notably for use as β-lactamase inhibitors, notably in the treatment of a disease caused by gram negative bacteria, in particular enterobacteria, as well as pharmaceutical compositions containing such a compound and a process to prepare such a compound.

NEW ANTIBIOTICS TARGETING MYCOBACTERIA

The present invention relates to a compound of the following formula (I) or a pharmaceutically acceptable salt and/or solvate thereof, notably for use as a drug, notably in the treatment of a disease caused by mycobacteria, as well as pharmaceutical compositions containing such a compound and a process to prepare such a compound.

NOVEL HETEROCYCLIC COMPOUNDS AND THEIR USE IN PREVENTING OR TREATING BACTERIAL INFECTIONS

The present invention relates to compound of formula (I) and their use for treating bacterial infections.

7-oxo-diazabicyclo [3, 2, 1] octane derivative compound, preparation method thereof and application

The invention relates to a 7-oxo-diazabicyclo [3, 2, 1] octane derivative compound, a preparation method thereof and an application, and belongs to the technical field of drug synthesis, and aims to solve the problem of how to obtain high-activity antibacterial drugs. The method includes the steps: performing condensation reaction of a compound in a formula IV and RH to obtain an intermediate product compound in a formula V in the presence of acid-binding agents; removing benzyl by hydrogenation deprotection treatment and then performing sulfonation or phosphorylation reaction to obtain the 7-oxo-diazabicyclo [3, 2, 1] octane derivative compound in a formula I. The RH is selected from substituted or unsubstituted 1H-1, 2, 3-triazole or 1H-1, 2, 4-triazole compound, and compounds in the formula VI or VII are in one-to-one correspondence to R2, R3 and R4 in the compound in the formula I. The derivative compound has good antibacterial activity and particularly has good inhibiting effects on pseudomonas aeruginosa and Escherichia coli, the method is simple in operation, and conditions are mild.

A PROCESS FOR PREPARATION OF SODIUM (2S, 5R)-6-(BENZYLOXY)-7-OXO-1,6-DIAZABICYCLO[3.2.1]OCTANE-2-CARBOXYLATE

A process for preparation of a compound of Formula (I) is disclosed.

NITROGEN CONTAINING COMPOUNDS AND THEIR USE

Compound of Formula (I), its preparation and use in preventing or treating bacterial infection is disclosed. Formula (I)