1174020-63-3

Upstream product

• 32315-10-9 bis(trichloromethyl) carbonate 
• 1510832-19-5 4-((2S,5R)-((benzyloxy)amino)piperidine-2-carboxamido)piperidine-1-carboxylic acid tert-butyl ester 
• 1510832-11-7 C₃₅H₄₂N₆O₁₂S₂ 
• 1510832-15-1 (1S,4S)-5-((2-nitrophenyl)sulfonyl)-2-oxa-5-azabicyclo[2.2.2]octan-3-one 
• 63088-78-8 (2S,5R)-5-hydroxypiperidine-2-carboxylic acid 
• 1510832-12-8 C₁₂H₁₄N₂O₇S 
• 1510832-18-4 tert-butyl 4-((2S,5S)-1-((2-nitrophenyl)sulfonyl)-5-(((2-nitrophenyl)sulfonyl)oxy)piperidine-2-carboxamido)piperidine-1-carboxylate 
• 87120-72-7 1-(tert-butoxycarbonyl)-4-aminopiperidine 
• 75-78-5 dimethylsilicon dichloride 
• 530-62-1 1,1'-carbonyldiimidazole 
• 1174020-25-7 (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 

Downstream Products

• 1174018-99-5 (2S,5R)-sulfuric acid mono{[(4-aminopiperidin-4-yl)carbonyl]-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl}ester 

Relevant academic research and scientific papers

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.

DERIVATIVES OF RELEBACTAM AND USES THEREOF

Derivatives of relebactam, therapeutic methods of using the derivatives of relebactam, particularly in combination with β-lactam antibiotics and pharmaceutical compositions thereof are disclosed. The derivatives of relebactam are suitable for oral administration.

Simple preparation method of Relebactam intermediate

The invention discloses a simple preparation method of Relebactam intermediate, namely (2S,5R)-N-(1-protective group) piperidine-4-yl-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane - 2- formamide, (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonyl chloride is prepared from (2S, 5R) -5- benzyloxaminopiperidine -2- formic acid and phosgene, solid phosgene or diphosgene in a solventin the presence of an alkali and a catalyst by epoxidation and acylating chlorination reaction by a one-pot method, and the (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonyl chlorideis not separated and is directly subjected to amidation reaction with (1-protective group)-4-amino piperidine to obtain the (2S,5R)-N-(1-protective group) piperidine-4-yl-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane - 2- formamide. The method disclosed by the invention is simple in steps, cheap and easily available in raw materials, green and environment-friendly in process, low in cost, high in reaction atom economy, high in purity, yield and selectivity of the obtained intermediate, and beneficial to industrial production.

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.

PROCESS FOR THE PREPARATION OF TERT-BUTYL 4-((2S,5R)-6-(BENZYLOXY)-7-OXO-1,6-DIAZABICYCLO[3.2.1]OCTANE-2-CARBOXAMIDO)PIPERIDINE-1-CARBOXYLATE AND ANALOGS THEREOF

The present invention relates to processes for preparing compounds of Formula I. Such compounds include intermediates in the manufacture of 7-oxo-1,6- diazabicyclo[3.2.1 ]octane-2-carboxamide beta-lactamase inhibitors such as (2S,5R)-7-oxo-N- 5 piperidin-

A PROCESS FOR PREPARATION OF (2S, 5R)- SULFURIC ACID MONO-{[(4-AMINOPIPERIDIN-4-YL) CARBONYL]-7-OXO-1,6-DIAZA-BICYCLO[3.2.1]-OCT-6-YL} ESTER

A process for preparation of (2S, 5R)- Sulfuric acid mono-{[(4- aminopiperidin-4-yl) carbonyl]-7-oxo-1,6-diaza-bicyclo[3.2.1]-oct-6-yl} ester is disclosed which comprises reacting a compound of Formula (II) with a compound of Formula (III) to obtain a compound of Formula (IV).

Practical and cost-effective manufacturing route for the synthesis of a β-lactamase inhibitor

Compound 1, a potent and irreversible inhibitor of β-lactamases, is in clinical trials with β-lactam antibiotics for the treatment of serious and antibiotic-resistant bacterial infections. A short, scalable, and cost-effective route for the production of this densely functionalized polycyclic molecule is described.

Discovery of MK-7655, a β-lactamase inhibitor for combination with Primaxin

β-Lactamase inhibitors with a bicyclic urea core and a variety of heterocyclic side chains were prepared and evaluated as potential partners for combination with imipenem to overcome class A and C β-lactamase mediated antibiotic resistance. The piperidine analog 3 (MK-7655) inhibited both class A and C β-lactamases in vitro. It effectively restored imipenem's activity against imipenem-resistant Pseudomonas and Klebsiella strains at clinically achievable concentrations. A combination of MK-7655 and Primaxin is currently in phase II clinical trials for the treatment of Gram-negative bacterial infections.

BETA-LACTAMASE INHIBITORS

Substituted bicyclic beta-lactams of Formula I: (I), are ?-lactamase inhibitors, wherein a, X, R1 and R2 are defined herein. The compounds and pharmaceutically acceptable salts thereof are useful in the treatment of bacterial infections in combination with ?-lactam antibiotics. In particular, the compounds can be employed with a ?-lactam antibiotics (e.g., imipenem, piperacillin, or ceftazidime) against microorganisms resistant to ?-lactam antibiotics due to the presence of the ?-lactamases.