Amikacin

Base Information

• Chemical Name: Amikacin
• CAS No.: 37517-28-5
• Deprecated CAS: 108914-65-4,38859-32-4,110660-81-6,111319-93-8,110660-83-8,1079316-47-4,1079316-47-4,110660-83-8,111319-93-8,38859-32-4
• Molecular Formula: C22H43N5O13
• Molecular Weight: 585.609
• Hs Code.: 29419090
• European Community (EC) Number: 253-538-5
• UNII: 84319SGC3C
• DSSTox Substance ID: DTXSID3022586
• Nikkaji Number: J19.345C
• Wikipedia: Amikacin
• Wikidata: Q408529
• NCI Thesaurus Code: C61615
• RXCUI: 641
• Metabolomics Workbench ID: 42825
• ChEMBL ID: CHEMBL177
• Mol file: 37517-28-5.mol

Synonyms:A.M.K;Amikacin;Amikacin Sulfate;Amikacina Medical;Amikacina Normon;Amikafur;Amikalem;Amikason's;Amikayect;Amikin;Amiklin;Amukin;BB K 8;BB K8;BB-K 8;BB-K8;BBK 8;BBK8;Biclin;Biklin;Gamikal;Kanbine;Medical, Amikacina;Normon, Amikacina;Oprad;Sulfate, Amikacin;Yectamid

Chemical Property of Amikacin

Chemical Property:

• Melting Point: 203-204oC (sesquihydrate)
• Refractive Index: 1.663
• Boiling Point: 981.8 °C at 760 mmHg
• PKA: pKa 8.1 (Uncertain)
• Flash Point: 547.6 °C
• PSA: 331.94000
• Density: 1.6 g/cm³
• LogP: -5.23210
• Storage Temp.: 2-8°C
• Solubility.: H2O: 50 mg/mL, clear, colorless
• Water Solubility.: Soluble in water (partly).
• XLogP3: -7.9
• Hydrogen Bond Donor Count: 13
• Hydrogen Bond Acceptor Count: 17
• Rotatable Bond Count: 10
• Exact Mass: 585.28573644
• Heavy Atom Count: 40
• Complexity: 819

Purity/Quality:

99% ^*data from raw suppliers

Amikacin hydrate ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-24/25

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Aminoglycosides
• Canonical SMILES: C1C(C(C(C(C1NC(=O)C(CCN)O)OC2C(C(C(C(O2)CO)O)N)O)O)OC3C(C(C(C(O3)CN)O)O)O)N
• Isomeric SMILES: C1[C@@H]([C@H]([C@@H]([C@H]([C@@H]1NC(=O)[C@H](CCN)O)O[C@@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)N)O)O)O[C@@H]3[C@@H]([C@H]([C@@H]([C@H](O3)CN)O)O)O)N
• Recent ClinicalTrials: Antimicrobial Prophylaxis in Patients Who Underwent a Transurethral Resection of Bladder (TURB)
• Recent EU Clinical Trials: A Phase 3, Multi-Center, Randomized, Single-Blind Study to Assess the Efficacy and Safety of Cefepime/Nacubactam and Aztreonam/Nacubactam Versus Best Available Therapy in Adults With Complicated Urinary Tract Infection, Acute Uncomplicated Pyelonephritis, Hospital-Acquired Bacterial Pneumonia, Ventilator-Associated Bacterial Pneumonia, and Complicated Intra-Abdominal Infection due to Carbapenem-Resistant Enterobacterales
• Recent NIPH Clinical Trials: The safety and feasibility of inhaled amikacin for treatment of refractory chronic lower respiratory tract infections
• Description: Amikacin is made semisynthetically from kanamycin A. Interestingly, the L-hydroxyaminobutyryl amide (HABA) moiety attached to N-3 inhibits adenylation and phosphorylation in the distant amino sugar ring (at C-2′and C-3′), even though the HABA substituent is not where the enzymatic reaction takes place. This effect is attributed to decreased binding to the R factor–mediated enzymes.
• Uses: Amikacin is highly effective with respect to Gram-negative microorganisms (blue-pus and gastric bacilli, rabbit fever, serratia, providencia, enterobacteria, proteus, salmonella, shigella), as well as Gram-positive microorganisms (staphylococci, including those that are resistant to penicillin and some cephalosporins), and a few strains of streptococci.It is used for severe bacterial infections: peritonitis, sepsis, meningitis, osteomyelitis, endocarditis, pneumonia, pleural empyema, pulmonary abscess, purulent skin and soft tissue infections, and infections of the urinary tract that are caused by microorganisms sensitive to the drug. Synonyms of this drug are amikin, biklin, novamin, and others. Antibacterial;Ribosomal protein synthesis inhibitor Amikacin is a semi-synthetic derivative of kanamycin. It is much less sensitive to the enzymes that inactivate aminoglycoside antibiotics. The spectrum is similar to that of gentamicin. Amikacin principally finds use in the treatment of infections arising from bacteria that are resistant to gentamicin and/or tobramycin.
• Therapeutic Function: Antibacterial
• Clinical Use: Amikacin, 1-N-amino-α-hydroxybutyrylkanamycin A(Amikin), is a semisynthetic aminoglycoside first preparedin Japan. The synthesis formally involves simple acylationof the 1-amino group of the deoxystreptamine ring ofkanamycin A with L-AHBA. This particular acyl derivativeretains about 50% of the original activity of kanamycin Aagainst sensitive strains of Gram-negative bacilli. The LAHBAderivative is much more active than the D-isomer.The remarkable feature of amikacin is that it resists attackby most bacteria-inactivating enzymes and, therefore, is effectiveagainst strains of bacteria that are resistant to otheraminoglycosides, including gentamicin and tobramycin.In fact, it is resistant to all known aminoglycoside-inactivatingenzymes, except the aminotransferase that acetylates the6 amino group and the 4'-nucleotidyl transferase thatadenylylates the 4'-hydroxyl group of aminoglycosides.Preliminary studies indicate that amikacin may be lessototoxic than either kanamycin or gentamicin. Higherdosages of amikacin are generally required, however, for the treatment of most Gram-negative bacillary infections. Forthis reason, and to discourage the proliferation of bacterialstrains resistant to it, amikacin currently is recommended forthe treatment of serious infections caused by bacterialstrains resistant to other aminoglycosides. Severe infection (including septicemia, neonatal sepsis, osteomyelitis, septic arthritis, respiratory tract, urinary tract, intra-abdominal, peritoneal and soft tissue infections) caused by susceptible micro-organisms Sepsis of unknown origin (combined with a β-lactam or anti-anaerobe agent as appropriate). Mycobacterial infection Amikacin is principally used for the treatment of infections caused by organisms resistant to other aminoglycosides because of their ability to degrade them. Peak concentrations on 15 mg/kg once daily administration should exceed 45 mg/L, and trough concentration of <5 mg/L should be maintained to achieve therapeutic effects.
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: increased risk of nephrotoxicity with colistimethate or polymyxins and possibly cephalosporins; increased risk of ototoxicity and nephrotoxicity with capreomycin or vancomycin. Ciclosporin: increased risk of nephrotoxicity. Cytotoxics: increased risk with platinum compounds of nephrotoxicity and possibly of ototoxicity Diuretics: increased risk of ototoxicity with loop diuretics. Muscle relaxants: enhanced effects of nondepolarising muscle relaxants and suxamethonium. Parasympathomimetics: antagonism of effect of neostigmine and pyridostigmine. Tacrolimus: increased risk of nephrotoxicity.

Technology Process of Amikacin

There total 12 articles about Amikacin 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: 99.5%

C67H133N5O15Si10 → amikacin (37517-28-5)

Guidance literature:

With hydrogen bromide; In water; pH=2 - 3;

Reference yield: 99.0%

C30H45N5O15 → amikacin (37517-28-5)

Guidance literature:

With hydrazine hydrate; for 4h; Reflux;

Reference yield: 93.6%

γ-phthalimidoimino-α-hydroxybutyric acid (40732-91-0,31701-91-4) → amikacin (37517-28-5)

Guidance literature:

γ-phthalimidoimino-α-hydroxybutyric acid; With 2-Mercaptobenzothiazole; triethylamine; In dichloromethane; at 20 ℃; for 3h;

silyl kanamycin A; In dichloromethane; at 0 - 5 ℃; for 5h; Further stages;

upstream raw materials:

amikacin sulfate

kanamycin A

γ-phthalimidoimino-α-hydroxybutyric acid

Downstream raw materials:

1-N-[4-(tert-butoxycarbonyl)amino-2-S-hydroxybutyryl]kanamycin A

6'-N-(tert-butoxycarbonyl)-1-N-[4-(tert-butoxycarbonyl)amino-2-S-hydroxybutyryl]-kanamycin A

C₄₂H₇₅N₅O₂₁

amikacin sulfate

Refernces

• 1、 -. "Preparation method for amikacin". Paragraph 0024-0037; 0040-0042. . Retrieved 2020/06/24.
• 2、 -. "Preparation method of amikacin and intermediate active ester thereof". Paragraph 0099; 0103. . Retrieved 2019/01/08.