Avibactam sodium

Avibactam sodium 속성

Avibactam sodium C화학적 특성, 용도, 생산

개요

Avibactam sodium (NXL-104), a diazabicyclooctanone compound, is currently the most favoured novel β-lactamase inhibitor. Compared with the three marketed β-lactamase inhibitors, NXL-104 has a long duration of action and reversible covalent binding to the enzyme, and does not induce β-lactamase production.

Characteristics

Avibactam sodium is a novel beta-lactamase inhibitor. In its structure, Na+ readily forms coordination bonds with water molecules. In addition, there are several O atoms as hydrogen bond acceptors and -NH2 as hydrogen bond donors. As a result, avibactam sodium crystallises easily into its hydrated form^[1]. The structure is shown below:

역사

Avibactam sodium and its free acid, avibactam, are diazabicyclooctane (DBO)–based, non-β-lactam β-lactamase inhibitors (BLIs) that are used to treat multi-drug–resistant Gram-negative bacterial pathogens. The compounds were jointly developed by Actavis Generics (now part of Teva Pharmaceutical Industries) and AstraZeneca.
In 2015, avibactam sodium, in combination with ceftazidime, a cephalosporin antibiotic, was approved by the US Food and Drug Administration. The dual-drug’s target was complex urinary tract and intra-abdominal infections caused by Gram-negative, often hospital-acquired, bacteria.
In 2018, in the continuing quest to combat multi-drug–resistant bacteria, Eric M. Gordon, Matthew A. J. Duncton, and Mark A. Gallop at Arixa Pharmaceuticals (Palo Alto, CA) prepared analogues of avibactam that are more orally available than the free acid or its salt.

용도

Avibactam (NXL104) is a novel β-lactamase inhibitor with a non-lactam structural scaffold. NXL104 irreversibly inhibits lactamase from Mycobacterium tuberculosis.

정의

ChEBI: Avibactam sodium is an organic sodium salt that is the monosodium salt of avibactam. Used in combination with ceftazidime pentahydrate for the treatment of complicated urinary tract infections including pyelonephritis. It has a role as an EC 3.5.2.6 (beta-lactamase) inhibitor, an antibacterial drug and an antimicrobial agent. It contains an avibactam(1-).

생물학적 활성

Avibactam[1192491-61-4] is a β-lactamase inhibitor (IC50s = 8, 80, and 38 nM for TEM-1, P99, and KPC-2 β-lactamases, respectively). It restores the antimicrobial activity of ceftazidime , ceftriaxone , imipenem , and piperacillin against antibiotic-resistant Enterobacteriaceae in vitro (MIC90 reduction 4-1,024-fold across 190 E. coli and K. pneumoniae clinical isolates). Formulations containing avibactam have been used to treat carbapenem-resistant Enterobacteriaceae infections.

Synthesis

A solution of sodium 2-ethyl hexanoate (475.0 g, 2.850 mol) in ethanol (2.00 L) was added to a solution of tetrabutylammonium [(2S,5R)-2-carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl] sulfate 13 (723.0 g) in ethanol (2.50 l) and water (50 mL) over approximately 1 h, and the temperature was maintained at rt. The reaction mixture was held for 2 h. The product was filtered, washed with ethanol (2 × 2.0 L), and dried to yield a white crystalline solid 1 (395.0 g, 96.2%), mp 259.1–262.4 °C (decomposition); [α]D20 = ?46.40 (c = 0.79, MeOH/H2O = 1/1); 1H NMR (500 MHz, D2O) δ 4.15 (dd, J = 5.8, 2.8 Hz, 1H), 4.01 (d, J = 7.5 Hz, 1H), 3.28 (d, J = 12.2 Hz, 1H), 3.06 (d, J = 12.2 Hz, 1H), 2.23–2.09 (m, 1H), 2.06–1.96 (m, 1H), 1.94–1.82 (m, 1H), 1.81–1.69 (m, 1H). 13C NMR (126 MHz, D2O) δ 174.72 (s), 169.53 (s), 60.43 (s), 59.93 (s), 47.33 (s), 20.03 (s), 18.31 (s). IR (cm–1): 3459, 1749, 1675, 1361, 1270, 1013, 857, 768. MS (ESI) m/z: 279.0 [M + H]+.

참고 문헌

[1] STACHYRATHéRèSE. Mechanistic studies of the inactivation of TEM-1 and P99 by NXL104, a novel non-beta-lactam beta-lactamase inhibitor.[J]. Antimicrobial Agents and Chemotherapy, 2010: 5132-5138. DOI:10.1128/AAC.00568-10.
[2] BONNEFOYALAIN. In vitro activity of AVE1330A, an innovative broad-spectrum non-beta-lactam beta-lactamase inhibitor.[J]. Journal of Antimicrobial Chemotherapy, 2004, 54 2: 410-417. DOI:10.1093/jac/dkh358.
[3] LAGACé-WIENSP R S. Activity of NXL104 in combination with beta-lactams against genetically characterized Escherichia coli and Klebsiella pneumoniae isolates producing class A extended-spectrum beta-lactamases and class C beta-lactamases.[J]. Antimicrobial Agents and Chemotherapy, 2011, 55 5: 2434-2437. DOI:10.1128/AAC.01722-10.
[4] KINGMADELINE. Multicenter Study of Outcomes with Ceftazidime-Avibactam in Patients with Carbapenem-Resistant Enterobacteriaceae Infections.[J]. Antimicrobial Agents and Chemotherapy, 2017, 61 7. DOI:10.1128/AAC.00449-17.
[5] ZHIYONG DING. Understanding the Role of Water in Different Solid Forms of Avibactam Sodium and Its Affecting Mechanism[J]. Crystal Growth & Design, 2020, 20 2: 1150-1161. DOI:10.1021/acs.cgd.9b01459.
[6] TAO WANG. A New Synthetic Route to Avibactam: Lipase Catalytic Resolution and the Simultaneous Debenzylation/Sulfation[J]. Organic Process Research & Development, 2017, 22 3: 267-272. DOI:10.1021/acs.oprd.7b00290.

Avibactam sodium 준비 용품 및 원자재

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Avibactam sodium 공급 업체

공급자	전화	이메일	국가	제품 수	이점
Wuhan Jingkang en Biomedical Technology Co., Ltd	+8613720134139	orders@jknbiochem.com	China	5221	58
S&Y Biochem Co.,Ltd	+8617774091612	marketing@sybiochem.com	China	283	58
Hebei Mujin Biotechnology Co.,Ltd	+86-13288715578 +86-13288715578	sales@hbmojin.com	China	12747	58
shandong perfect biotechnology co.ltd	+86-53169958659 +86-13153181156	sales@sdperfect.com	China	294	58
airuikechemical co., ltd.	+86-18353166132 +86-18353166132	sales02@airuikechemical.com	China	983	58
hebei hongtan Biotechnology Co., Ltd	+852-6619 3215 +86-17731935328	sales03@chemcn.cn	China	970	58
BEIJING SJAR TECHNOLOGY DEVELOPMENT CO., LTD.	+86-18600796368 +86-18600796368	sales@sjar-tech.com	China	485	58
Cangzhou Kangrui Pharma Tech Co. Ltd.,	+86-18632776803 +86-13833998158	cangzhoukangrui@126.com	China	751	58
Capot Chemical Co.,Ltd.	+8613336195806	sales@capot.com	China	29731	60
Beijing Cooperate Pharmaceutical Co.,Ltd	010-60279497	sales01@cooperate-pharm.com	CHINA	1803	55

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