- Use:antibiotic
- Chemical name:[6R-[6α,7β(R*)]]-7-[(hydroxyphenylacetyl)amino]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
- Formula:C18H18N6O5S2
- MW:462.51 g/mol
- CAS-RN:34444-01-4
- InChI Key:OLVCFLKTBJRLHI-AXAPSJFSSA-N
- InChI:InChI=1S/C18H18N6O5S2/c1-23-18(20-21-22-23)31-8-10-7-30-16-11(15(27)24(16)12(10)17(28)29)19-14(26)13(25)9-5-3-2-4-6-9/h2-6,11,13,16,25H,7-8H2,1H3,(H,19,26)(H,28,29)/t11-,13-,16-/m1/s1
- EINECS:252-030-0
Derivatives
Formate monosodium salt (nafate)
- Formula:C19H17N6NaO6S2
- MW:512.50 g/mol
- CAS-RN:42540-40-9
- EINECS:255-877-4
- LD50:3915 mg/kg (M, i.v.);
2562 mg/kg (R, i.v.)
Cefamandole (INN, also known as cephamandole) is a second-generation broad-spectrumcephalosporinantibiotic. The clinically used form of cefamandole is the formateestercefamandole nafate, a prodrug which is administered parenterally. Cefamandole is no longer available in the United States.
The chemical structure of cefamandole, like that of several other cephalosporins, contains an N-methylthiotetrazole (NMTT or 1-MTT) side chain. As the antibiotic is broken down in the body, it releases free NMTT, which can cause hypoprothrombinemia (likely due to inhibition of the enzymevitamin K epoxide reductase)(vitamin K supplement is recommended during therapy) and a reaction with ethanol similar to that produced by disulfiram (Antabuse), due to inhibition of aldehyde dehydrogenase.
Cefamandole has a broad spectrum of activity and can be used to treat bacterial infections of the skin, bones and joints, urinary tract, and lower respiratory tract. The following represents cefamandole MIC susceptibility data for a few medically significant microorganisms.
- Escherichia coli: 0.12 – 400 μg/ml
- Haemophilus influenzae: 0.06 – >16 μg/ml
- Staphylococcus aureus: 0.1 – 12.5 μg/ml
CO2 is generated during the normal constitution of cefamandole and ceftazidime, potentially resulting in an explosive-like reaction in syringes.[2]
SYNTHESIS
US 3641021
US 3840531 US 3974153 US 3903278 US 2018600 US 2065621 DE 2018600 DE 2065621 DE 2730579
DE 2312997
SYN
The formylation of 7-aminocephalosporanic acid (I) by the usual techniques produces 7-formamidocephalosporanic acid (II), which is then treated with the sodium salt of 1-methyl-1H-tetrazole-5-thiol (III) to yield 7-formamido-3-(1-methyl-1H-tetrazol-5-ylthio)methyl-3-cephem-4-carboxylic acid (IV). The resulting product (IV) is deformylated affording 7-amino-3-(1-methyl-1H-tetrazol-5-ylthio)methyl-3-cephem-4-carboxylic acid (V), which is finally acylated with anhydro-O-carboxymandelic acid (VI) using the usual techniques.
References
- ^ http://www.toku-e.com/Assets/MIC/Cefamandole%20sodium%20salt.pdf
- ^ Stork CM (2006). “Antibiotics, antifungals, and antivirals”. In Nelson LH, Flomenbaum N, Goldfrank LR, Hoffman RL, Howland MD, Lewin NA. Goldfrank’s toxicologic emergencies. New York: McGraw-Hill. p. 847. ISBN 0-07-143763-0. Retrieved 2009-07-03.
-
- US 3 641 021 (Lilly; 8.2.1972; appl. 18.4.1969).
- DE 2 018 600 (Lilly; appl. 17.4.1970; USA-prior. 18.4.1969).
- DAS 2 065 621 (Lilly; appl. 17.4.1970; USA-prior. 18.4.1969).
- US 3 840 531 (Lilly; 8.10.1974; appl. 21.3.1972).
- US 3 903 278 (Smith Kline Corp.; 2.9.1975; prior. 4.11.1971).
- DOS 2 730 579 (Pierrel S.p.A.; appl. 6.7.1977; GB-prior. 10.7.1976).
-
preparation and/or purification via the trimethylsilyl-derivatives:
- DOS 2 711 095 (Lilly; appl. 14.3.1977; USA-prior. 17.3.1976).
-
purification:
- US 4 115 644 (Lilly; 19.9.1978; appl. 19.9.1978).
- DOS 2 839 670 (Lilly; appl. 12.9.1978; USA-prior. 19.9.1977).
-
crystalline sodium salt:
- US 4 054 738 (Lilly; 18.10.1977; appl. 22.12.1975).
- US 4 168 376 (Lilly; 18.9.1979; appl. 5.6.1978).
-
lithium salt:
- GB 1 546 757 (Lilly; appl. 10.4.1975; valid from 7.4.1976).
-
O-formyl-derivative:
- US 3 928 592 (Lilly; 23.12.1975; appl. 21.2.1974).
- GB 1 493 676 (Lilly; appl. 20.2.1975; USA-prior. 22.2.1974).
- GB 1 546 898 (Lilly; appl. 7.4.1976; USA-prior. 11.4.1975).
- DOS 2 506 622 (Lilly; appl. 17.2.1975; USA-prior. 22.2.1974).
-
crystalline sodium salt of O-formylcefamandole:
- US 4 006 138 (Lilly; 1.2.1977; appl. 11.4.1975).
-
complex of cefamandole sodium with 1,4-dioxane and water:
- US 3 947 414 (Lilly; 30.3.1976; appl. 23.12.1974).
-
complex of cefamandole sodium with ethyl l-(–)-lactate:
- US 3 947 415 (Lilly; 30.3.1976; appl. 23.12.1974).
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| Clinical data | |
|---|---|
| Trade names | former Mandol |
| AHFS/Drugs.com | Micromedex Detailed Consumer Information |
| MedlinePlus | a601206 |
| Pregnancy category |
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| Routes of administration |
Intramuscular, intravenous |
| ATC code | |
| Legal status | |
| Legal status |
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| Pharmacokinetic data | |
| Protein binding | 75% |
| Elimination half-life | 48 minutes |
| Excretion | Mostly renal, as unchanged drug |
| Identifiers | |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
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| ChEBI | |
| ChEMBL | |
| ECHA InfoCard | 100.047.285  |
| Chemical and physical data | |
| Formula | C18H18N6O5S2 |
| Molar mass | 462.505 g/mol g·mol−1 |
| 3D model (JSmol) | |
