Meropenem

Base Information

• Chemical Name: Meropenem
• CAS No.: 96036-03-2
• Molecular Formula: C17H25N3O5S
• Molecular Weight: 383.469
• Hs Code.: 29419000
• European Community (EC) Number: 641-424-1,642-885-1
• UNII: YOP6PX0BAO
• DSSTox Substance ID: DTXSID7045526
• Nikkaji Number: J327.339C
• Wikipedia: Meropenem
• Wikidata: Q421670
• NCI Thesaurus Code: C61833
• RXCUI: 1546029
• Metabolomics Workbench ID: 43058
• ChEMBL ID: CHEMBL127
• Mol file: 96036-03-2.mol

Synonyms:3-(5-dimethylcarbamoylpyrrolidin-3-ylthio)-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid;meropenem;Merrem;Penem;Ronem;SM 7338;SM-7338;SM7338

Chemical Property of Meropenem

Chemical Property:

• Appearance/Colour: white powder
• Vapor Pressure: 2.27E-18mmHg at 25°C
• Refractive Index: 1.639
• Boiling Point: 627.4 °C at 760 mmHg
• PKA: 4.27±0.60(Predicted)
• Flash Point: 333.2 °C
• PSA: 135.48000
• Density: 1.42 g/cm³
• LogP: -0.04130
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility.: insoluble in EtOH; ≥19.15 mg/mL in DMSO; ≥9.88 mg/mL in H2O with ultrasonic
• XLogP3: -2.4
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 5
• Exact Mass: 383.15149208
• Heavy Atom Count: 26
• Complexity: 679

Purity/Quality:

99% ^*data from raw suppliers

Meropenem ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiinfective Agents
• Canonical SMILES: CC1C2C(C(=O)N2C(=C1SC3CC(NC3)C(=O)N(C)C)C(=O)O)C(C)O
• Isomeric SMILES: C[C@@H]1[C@@H]2[C@H](C(=O)N2C(=C1S[C@H]3C[C@H](NC3)C(=O)N(C)C)C(=O)O)[C@@H](C)O
• Recent ClinicalTrials: Study of Cefepime-zidebactam (FEP-ZID) in Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)
• Recent EU Clinical Trials: Accelerated treatment of infectious endocarditis
• Recent NIPH Clinical Trials: Study on Pharmacokinetics and Pharmacodynamics of high dose Meropenem.
• Indications: Clinically, meropenem is suitable for treating the following infections caused by susceptible strains: 1. Respiratory infections such as chronic bronchitis, nosocomial pneumonia, lung abscess and empyema. 2. Intra-abdominal infections such as cholecystitis, cholangitis, liver abscess and peritonitis. 3. Urinary and reproductive system infections, such as pyelonephritis and complicated cystitis, endometritis, adnexitis, intrauterine infections, pelvic inflammatory disease and uterine connective tissue. 4. Bones, joints and skin and soft tissue infections such as cellulitis, anal abscess, osteomyelitis, arthritis, trauma, wound infection, burn wound infections, surgical wound infections, maxilla and mandible surrounding cellulitis. 5. Eye and ENT infections. 6. Empirical treatment; for patients of adult neutropenia with fever, the drug can be used alone or be used in combination with antiviral or antifungal drugs. 7. It can be used either alone or in combination with other anti-microbial agents for the treatment of complex infections. 8. Other serious infections, such as meningitis, septicemia.
• Drug Interactions: 1. Combined therapy with probenecid can reduce the plasma clearance of meropenem while extending the half-life of meropenem. 2. Simultaneous application of typhoid vaccine may interfere with the immune response of live typhoid vaccine. 3. It has been reported that combination with antiepileptic drugs can reduce the plasma concentrations of anti-epileptic drugs. 4. Combination with zidovudine, ondansetron, vitamins, doxycycline, diazepam, calcium gluconate and acyclovir belong to combination compatibility.
• Uses: It is a kind of anti-infection drugs and a kind of antibiotics. antineoplastic, PDGF receptor blocker, immunomodulator Meropenem, is an ultra-broad spectrum injectable antibiotic used to treat a wide variety of infections, including meningitis and pneumonia.
• Description: Meropenem is a new carbapenem antibiotic introduced to market for the i.v. treatment of a wide variety of hospital infections such as lower respiratory tract, urinary tract, intraabdominal, gynecological and polymicrobial infections. Meropenem has a broad spectrum of antibacterial activity against most clinically important Gram-positive and Gramnegative aerobic and anaerobic bacteria with especially high potency against multiresistant Enterobacteriaceae and Pseudornonas aeruginosa. Compared with imipenem, the only other available carbapenem antibiotic, meropenem has the advantage of being dehydropeptidase 1 (DHP-1) stable and therefore does not need to be administered in conjunction with the DHP-1 inhibitor cilastatin. Meropenem is also being evaluated for treatment of resistant pseudomonal infections in cystic fibrosis patients.
• Clinical Use: Meropenem is a synthetic carbapenem possessing a complex side chain at C-3. It also has a chiral methyl group at C-4. This methyl group conveys intrinsic resistance to hydrolysis by dehydropeptidase-1. As a consequence, it can be administered as a single agent for the treatment of severe bacterial infections.

Technology Process of Meropenem

There total 35 articles about Meropenem which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 85.3%

p-nitrobenzyl (4R,5S,6S)-3-<(3S,5S)-5-dimethylaminocarbonyl-1-(p-nitrobenzyloxycarbonyl)pyrrolidin-3-ylthio>-6-<(1R)-1-hydroxyethyl>-4-methyl-7-oxo-1-azabicyclo<3.2.0>hept-2-en-2-carboxylate (96036-02-1) → meropenem (96036-03-2)

Guidance literature:

With 2,6-dimethylpyridine; hydrogen; In tetrahydrofuran; water; at 40 ℃; for 1.16667h; under 13446.2 Torr; Pressure; Temperature; Reagent/catalyst;

Reference yield: 44.0%

(1R,5R,6S)-6-[(1R)-1-hydroxymethyl]-2-diphenylphosphoryloxocarbapen-2-em-3-carboxylic acid p-nitrobenzyl ester + (2R,4S)-4-dimethylaminomercapto-2-formyl-1-p-nitrobenzyl carbonylpyrrolidine → meropenem (96036-03-2)

Guidance literature:

(1R,5R,6S)-6-[(1R)-1-hydroxymethyl]-2-diphenylphosphoryloxocarbapen-2-em-3-carboxylic acid p-nitrobenzyl ester; (2R,4S)-4-dimethylaminomercapto-2-formyl-1-p-nitrobenzyl carbonylpyrrolidine; at -5 ℃;

With 5%-palladium/activated carbon; hydrogen; at 25 ℃; Reagent/catalyst;

Reference yield:

indan-2-yloxycarbonyloxymethyl (1R,5S,6S)-2-{[(3S,5S)-5-(N,N-dimethylcarbamoyl)pyrrolidin-3-yl]thio}-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (1450666-26-8) → formaldehyd (50-00-0,30525-89-4,61233-19-0) + indan-2-ol (4254-29-9) + carbon dioxide (124-38-9,18923-20-1) + meropenem (96036-03-2)

Guidance literature:

With water; N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid; at 37 ℃; for 2h; pH=7.4; Reagent/catalyst; pH-value; Time; Mechanism;

DOI:10.1016/j.bmc.2013.05.024

upstream raw materials:

p-nitrobenzyl (4R,5S,6S)-3-<(3S,5S)-5-dimethylaminocarbonyl-1-(p-nitrobenzyloxycarbonyl)pyrrolidin-3-ylthio>-6-<(1R)-1-hydroxyethyl>-4-methyl-7-oxo-1-azabicyclo<3.2.0>hept-2-en-2-carboxylate

4-nitrobenzyl (4R,5S,6S)-3-[[(3S,5S)-5-(dimethylcarbamoyl)-3-pyrrolidinyl]thio]-6-[(1R)-1-hydroxy-ethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

(2S,4S)-1-p-nitrobenzyloxycarbonyl-2-dimethylaminocarbonyl-4-thiolpyrrolidine

(4-nitrophenyl)methyl (4R,5R,6S)-3-[(diphenoxyphosphinyl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

Downstream raw materials:

C₁₇H₂₇N₃O₆S

sodium (1R,5S,6S)-2-[(3S,5S)-5-(N,N-dimethylcarbamoyl)-1-(isobutyryloxymethyloxycarbonyl)pyrrolidin-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate

(4R,5S,6S)-3-((3S,5S)-1-(5-(2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(3,3-dimethyl-2-oxopentanoyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetamido)pentyl)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

(4R,5S,6S)-3-((3S,5S)-1-benzyl-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

Refernces

• 1、 -. "Method for preparing medicine and medicine intermediate by continuous solid-liquid-gas three-phase reaction". Paragraph 0035; 0036; 0037; 0041; 0049; 0050; 0053; 0054. . Retrieved 2018/07/30.
• 2、 -. "A raw meluopeinan, method for preparing the same and pharmaceutical composition containing the same". Paragraph 0154-0157. . Retrieved 2016/10/08.