1174018-99-5

Usage

Uses

Used in Pharmaceutical Industry:
Sulfuric acid Mono-[7-oxo-2-(piperidin-4-ylcarbaMoyl)-1,6-diaza-bicyclo[3.2.1]oct-6-yl] ester is used as an intermediate in the synthesis of various pharmaceutical compounds for [application reason]. Its unique chemical structure allows for the development of new drugs with specific targeting and therapeutic properties.
Used in Chemical Research:
In the field of chemical research, Sulfuric acid Mono-[7-oxo-2-(piperidin-4-ylcarbaMoyl)-1,6-diaza-bicyclo[3.2.1]oct-6-yl] ester serves as a valuable compound for studying reaction mechanisms, exploring new synthetic routes, and understanding the relationship between chemical structure and biological activity.
Used in Material Science:
Sulfuric acid Mono-[7-oxo-2-(piperidin-4-ylcarbaMoyl)-1,6-diaza-bicyclo[3.2.1]oct-6-yl] ester can be used as a building block for the development of novel materials with specific properties, such as improved stability, reactivity, or selectivity in various applications.

Mechanism of action

Relebactam is a beta-lactamase inhibitor known to inhibit many types of beta-lactamases including Ambler class A and Ambler class C enzymes, helping to prevent imipenem from degrading in the body.Label,Similar to the structurally-related avibactam, first, relebactam binds non-covalently to a beta-lactamase binding site, then, it covalently acylates the serine residue in the active site of the enzyme.In contrast to some other beta-lactamase inhibitors, once relebactam de-acylates from the active site, it can reform it's 5 membered ring and is capable of rebinding to target enzymes.https://go.drugbank.com/drugs/DB12377

Clinical Use

Recently, another carbapenem-β-lactamase inhibitor, imipenem/cilastatin-relebactam (RecarbrioTM), was approved by the FDA. Relebactam, a bicyclic diazabicyclooctane, is structurally related to avibactam but differs by the addition of a piperidine ring to the 2-position carbonyl group. Like meropenem- vaborbactam (VabomereTM), imipenem-relebactam(RecarbrioTM) is active against class A and class C carbapenemases and is approved for the treatment of multidrug-resistant intraabdominal infections secondary to Bacteroides caccae, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium stercoris, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Fusobacterium nucleatum, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Parabacteroides distasonis, and Pseudomonas aeruginosa and multidrug-resistant complicated urinary tract infections secondary to E. cloacae, E. coli, K. aerogenes, K. pneumoniae and P. aeruginosa.

Synthesis

Relebactam(MK-7655) is a β-lactamase inhibitor in clinical trials as a combination therapy for the treatment of bacterial infection resistant to β-lactam antibiotics. Its unusual structural challenges have inspired a rapid synthesis featuring an iridium-catalyzed N–H insertion and a series of late stage transformations designed around the reactivity of the labile bicyclo[3.2.1]urea at the core of the target.In 2014, Qualified Infectious Disease Product (QIDP) and Fast Track designations were assigned by the FDA for the treatment of complicated urinary tract infections, complicated intra-abdominal infections and hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia.A Concise Synthesis of a β-Lactamase Inhibitor

Upstream product

• 1510832-19-5 4-((2S,5R)-((benzyloxy)amino)piperidine-2-carboxamido)piperidine-1-carboxylic acid tert-butyl ester 
• 1510832-18-4 tert-butyl 4-((2S,5S)-1-((2-nitrophenyl)sulfonyl)-5-(((2-nitrophenyl)sulfonyl)oxy)piperidine-2-carboxamido)piperidine-1-carboxylate 
• 1510832-12-8 C₁₂H₁₄N₂O₇S 
• 63088-78-8 (2S,5R)-5-hydroxypiperidine-2-carboxylic acid 
• 1510832-15-1 (1S,4S)-5-((2-nitrophenyl)sulfonyl)-2-oxa-5-azabicyclo[2.2.2]octan-3-one 
• 1510832-11-7 C₃₅H₄₂N₆O₁₂S₂ 
• 1174020-64-4 tert-butyl 4-((2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamido)piperidine-1-carboxylate hydrate 
• 1174020-63-3 tert-butyl 4-((1R,2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamido)piperidine-1-carboxylate 
• 1174020-25-7 (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 
• 98-79-3 L-Pyroglutamic acid 
• 1174020-66-6 C₁₈H₂₃N₃O₄ 
• 1174020-21-3 4-({[(2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octan-2-yl]carbonyl}amino)piperidine-1-carboxylic acid benzyl ester 
• 1174020-18-8 tert-butyl (2S,5S)-2-[({1-[(benzyloxy)carbonyl]piperidin-4-yl}amino)carbonyl]-5-({[4-(trifluoromethyl)phenyl]sulfonyl}oxy)piperidine-1-carboxylate 
• 1174020-17-7 tert-butyl (2S)-2-[({1-[(benzyloxy)carbonyl]piperidin-4-yl}amino)carbonyl]-5-oxopiperidine-1-carboxylate 

Relevant academic research and scientific papers

PROCESS FOR O-SULFONATION OF 1,6-DIAZABICYCLO[3.2.1]OCTANE COMPOUNDS

A process for preparation of a compound of Formula (I), or a salt thereof is disclosed.

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.

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).

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.

PREPARATION OF TERT-BUTYL 4-((1R,2S,5R)-6- (BENZYLOXY)-7-0X0-1,6-DIAZABICYCL0[3.2.I]OCTANE-2- CARBOXAMIDO)PIPERIDINE-1-CARBOXYLATE

A process for the preparation of N-protected 6-(piperidin-4-ylcarbamoyl)piperidin-3-yl sulfonates of Formula (III): which comprises contacting a lactone of Formula (II): with an azacycloalkylamine of formula (II-Am): followed by contact with a sulfonyl halide of formula (II-Su): R4-SO2W (II-Su) in the presence of tertiary amine base, wherein PG1 and PG2 are amine protective groups; k, p and q are 0, 1, or 2, and W, R2, R3, R4, R5, R6, R7, R8, and R9 are defined herein. Additional embodiments add a series of process steps leading to the synthesis of 7-oxo-1,6-diazabicyclo[3.2.1]octanes suitable for use as β-lactamase inhibitors.

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.

A concise synthesis of a β-lactamase inhibitor

MK-7655 (1) is a β-lactamase inhibitor in clinical trials as a combination therapy for the treatment of bacterial infection resistant to β-lactam antibiotics. Its unusual structural challenges have inspired a rapid synthesis featuring an iridium-catalyzed N-H insertion and a series of late stage transformations designed around the reactivity of the labile bicyclo[3.2.1]urea at the core of the target.

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.