• ChemicalBook
    Chinese Japanese Germany Korea

    Minocycline

    Description References
    Minocycline
    Minocycline structure
    CAS No.
    10118-90-8
    Chemical Name:
    Minocycline
    Synonyms
    CS-588;cl59806;MINOCIN;MYNOCINE;minocyclin;MINOCYCLINE;MINOCYCLINE HCL;MinocyclineBase;Minocycline USP/EP/BP;Tigecycline Impurity 32
    CBNumber:
    CB7754621
    Molecular Formula:
    C23H27N3O7
    Formula Weight:
    457.48
    MOL File:
    10118-90-8.mol

    Minocycline Properties

    alpha 
    D25 -166° (c = 0.524)
    Boiling point:
    563.31°C (rough estimate)
    Density 
    1.3283 (rough estimate)
    refractive index 
    1.6500 (estimate)
    pka
    pKa 2.8 (Uncertain);5.0 (Uncertain);7.8 (Uncertain);9.5 (Uncertain)
    Water Solubility 
    52g/L(25 ºC)
    CAS DataBase Reference
    10118-90-8(CAS DataBase Reference)
    FDA UNII
    FYY3R43WGO
    EPA Substance Registry System
    Minocycline (10118-90-8)

    Minocycline Chemical Properties,Uses,Production

    Description

    Minocycline belongs to the class of medications called tetracycline antibiotics, who has a broader spectrum than the other members of the group. Identified as a long-acting type, it is used to treat infections induced by certain kinds of bacteria. Minocycline is commonly used in the treatment of skin infections, such as inflammatory lesions of non-nodular moderate-to-severe acne vulgaris. It is also used for other skin infections, such as MRSA and Lyme disease. Besides, minocycline is effective to treat urinary tract infections, gallbladder infections, and respiratory tract infections like bronchitis, pneumonia, sinusitis and it is also used for treating Rocky Mountain spotted fever, typhus and other infections caused by the typhus group of bacteria and tick fevers caused by rickettsiae, etc.
    Patented in 1961, minocycline was put into commercial use in 1971. It is not a naturally occurring antibiotic, but was synthesized semi-synthetically from natural tetracycline antibiotics by Lederle Laboratories in 1966.

    References

    https://en.wikipedia.org/wiki/Minocycline
    http://www.medicinenet.com/minocycline-oral/article.htm
    http://bodyandhealth.canada.com/drug/getdrug/ratio-minocycline

    Description

    An important antibiotic produced by semisynthesis from demeclocycline is minocycline. It is much more lipophilic than its precursors, gives excellent blood levels following oral administration (90–100% available),and can be given once a day. Its absorption is lowered by approximately 20% when taken with food or milk. It is less dependent on active uptake mechanisms and has a somewhat broader antimicrobial spectrum. It also, apparently, is less painful on IM or IV injection, but it has vestibular toxicities (e.g., vertigo, ataxia, and nausea) not generally shared by other tetracyclines.

    Originator

    Minocin,Lederle ,US,1971

    Uses

    Minocycline is used for the same indications as other antibiotics of the tetracycline series. In a few cases, it is tolerated worse than other tetracyclines, and in particular, it has an effect on the vestibular apparatus. In addition, as seen already from the synthesis scheme, it is much more expensive than other tetracyclines, which are synthesized in a purely microbiological manner. Synonyms of this drug are clinocin, minocyn, vectrin, and others.

    Uses

    Minocycline is a semi-synthetic tetracycline prepared by sequential hydrogenolysis, nitration and reductive methylation. Minocycline, together with doxycycline, is regarded as a ‘third generation’ tetracycline largely replacing the natural products and pro-drugs produced in the early 1950s for mainstream antibiotic applications. Like all tetracyclines, minocycline shows broad spectrum antibacterial and antiprotozoan activity and acts by binding to the 30S and 50S ribosomal sub-units, blocking protein synthesis. Minocycline has been extensively cited in the literature with over 5,000 references.

    Definition

    ChEBI: A tetracycline analogue having a dimethylamino group at position 7 and lacking the methyl and hydroxy groups at position 5.

    Indications

    The tetracycline antibiotic minocycline (Minocin) is modestly effective in the treatment of rheumatoid arthritis and is generally well tolerated. Radiographic evidence of its efficacy as a DMARD is lacking, although clinical symptoms do abate. It can be useful in the treatment of early, mild disease.

    Manufacturing Process

    Preparation of 7-(N,N'-Dicarbobenzyloxyhydrazino)-6-Demethyltetracycline: A1.0 g portion of 6-demethyltetracycline was dissolved in a mixture of 9.6 ml oftetrahydrofuran and 10.4 ml of methanesulfonic acid at -10°C. The mixturewas allowed to warm to 0°C. A solution of 0.86 g of dibenzyl azodicarboxylatein 0.5 ml of tetrahydrofuran was added dropwise and the mixture was stirredfor 2 hours while the temperature was maintained at 0°C. The reactionmixture was added to ether. The product was filtered off, washed with etherand then dried. The 7-(N,N'-dicarbobenzyloxyhydrazino)-6-demethyltetracycline was identified by paper chromatography.
    Reductive Methylation of 7-(N,N'-Dicarbobenzyloxyhydrazino)-6-Demethyl-6-Deoxytetracycline to 7-Dimethylamino-6-Demethyl-6-Deoxytetracycline: Asolution of 100 mg of 7(N,N'-dicarbobenzyloxyhydrazino)-6-demethyl-6-deoxytetracycline in 2.6 ml of methanol, 0.4 ml of 40% aqueous ormaldehyde solution and 50 mg of 5% palladium on carbon catalyst washydrogenated at room temperature and two atmospheres pressure. Uptake ofthe hydrogen was complete in 3 hours. The catalyst was filtered off and thesolution was taken to dryness under reduced pressure. The residue wastriturated with ether and then identified as 7-dimethylamino-6-demethyl-6-deoxytetracycline by comparison with an authentic sample, according to USPatent 3,483,251.

    brand name

    Dynacin (Medicis); Minocin (Lederle); Minocin (Triax); Solodyn (Medicis);Klinomycin;Lederderm;Mino-50;Minomycin.

    Therapeutic Function

    Antibiotic

    World Health Organization (WHO)

    Minocycline, a semi-synthetic tetracycline derivative was introduced in 1967. It is used today in the treatment of bacterial, rickettsial and amoebic infections. Symptoms described as dizziness or vertigo have been recognized in association with minocycline administration, however, these symptoms are usually not severe. Minocycline is registered in many countries and the World Health Organization is not aware that registration has been refused elsewhere.

    Antimicrobial activity

    It exhibits the broad-spectrum activity typical of the group, but retains activity against some strains of Staph. aureus resistant to older tetracyclines. It is active against β-hemolytic streptococci and some tetracycline- resistant pneumococci. It is also active against some enterobacteria resistant to other tetracyclines, probably because some Gram-negative efflux pumps remove minocycline less effectively than other tetracyclines. Some strains of H. influenzae resistant to other tetracyclines are susceptible. Sten. maltophilia is susceptible, as are most strains of Acinetobacter spp. and L. pneumophila.
    It is notable for its activity against Bacteroides and Fusobacterium spp., and is more active than other tetracyclines against C. trachomatis, brucellae and nocardiae. It inhibits Mycobacterium tuberculosis, M. bovis, M. kansasii and M. intracellulare at 5–6 mg/L. Candida albicans and C. tropicalis are also slightly susceptible.

    Pharmaceutical Applications

    A semisynthetic tetracycline derivative supplied as the hydrochloride for oral administration.

    Pharmacokinetics

    Oral absorption: 95–100%
    Cmax 150 mg oral: 4 mg/L after 2h
    300 mg oral: 2 mg/L after 2 h
    Plasma half-life: 12–24 h
    Volume of distribution: 80–115 L
    Plasma protein binding: 76%
    Absorption
    Food does not significantly affect absorption, which is depressed by co-administration with milk. It is chelated by metals and suffers the effects of antacids and ferrous sulfate common to tetracyclines. On a regimen of 100 mg every 12 h, steady-state concentrations ranged between 2.3 and 3.5 mg/L.
    Distribution
    The high lipophilicity of minocycline provides wide distribution and tissue concentrations that often exceed those of the plasma. The tissue:plasma ratio in maxillary sinus and tonsillar tissue is 1.6: that in lung is 3–4. Sputum concentrations may reach 37–60% of simultaneous plasma levels. In bile, liver and gallbladder the ratios are 38, 12 and 6.5, respectively.
    Prostatic and seminal fluid concentrations range from 40% to 100% of those of serum. CSF penetration is poor, especially in the non-inflamed state. Concentrations in tears and saliva are high, and may explain its beneficial effect in the treatment of meningococcal carriage.
    Metabolism
    Biotransformation to three microbiologically inactive metabolites occurs in the liver: the most abundant is 9-hydroxyminocycline.
    Excretion
    Only 4–9% of administered drug is excreted in the urine, and in renal failure elimination is little affected. Neither hemodialysis nor peritoneal dialysis affects drug elimination. Fecal excretion is relatively low and evidence for enterohepatic recirculation remains uncertain. Despite high hepatic excretion, dose accumulation does not occur in liver disease, such as cirrhosis. Type IIa and type IV hyperlipidemic patients show a decreased minocycline clearance of 50%, suggesting that dose modification may be necessary.

    Clinical Use

    There appear to be few situations in which it has a unique therapeutic advantage over other tetracyclines. Its use has been tempered by the high incidence of vestibular side effects.
    Although used in the long-term management of acne, the potential for skin pigmentation must be considered. Because of its high tissue concentrations, it may occasionally provide a useful alternative to other agents for the treatment of chronic prostatitis. It has a role in the treatment of sexually transmitted chlamydial infections.

    Side effects

    Minocycline shares the untoward reactions common to the group with gastrointestinal side effects being most common, and more prevalent in women. Diarrhea is relatively uncommon, presumably as a result of its lower fecal concentrations. Hypersensitivity reactions, including rashes, interstitial nephritis and pulmonary eosinophilia, are occasionally seen.
    Staining of the permanent dentition occurs with all tetracyclines; a side effect that appears to be unique to minocycline is that of tissue discoloration and skin pigmentation. Tissues that may become pigmented include the skin, skull and other bones and the thyroid gland, which at autopsy appears blackened. The pigmentation tends to resolve slowly with discontinuation of the drug and is related to the length of therapy.
    Three types of pigmentation have been identified:
    ? A brown macular discoloration (‘muddy skin syndrome’), which occurs in sun-exposed parts and is histologically associated with melanin deposition.
    ? Blue–black macular pigmentation occurring within inflamed areas and scars associated with hemosiderin deposition.
    ? Circumscribed macular blue–gray pigmented areas occurring in sun-exposed and unexposed skin, which appears to be linked to a breakdown product of minocycline.
    CNS toxicity has been prominent, notably benign intracranial hypertension, which resolves on discontinuation of the drug, and, more commonly, dizziness, ataxia, vertigo, tinnitus, nausea and vomiting, which appear to be more frequent in women. These primarily vestibular side effects have ranged in frequency from 4.5% to 86%. They partly coincide with plasma concentration peaks, but their exact pathogenesis has yet to be determined.

    Chemical Synthesis

    Minocycline, 4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12 a-octahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacencarboxamide (32.3.17), is synthesized from 6-dimethyl-tetracycline (32.3.11), which is synthesized as a result of the vital activity of S. aureofaciens, in which the mechanism of transferring methyl groups is disrupted, or from a common strain of the same microorganisms, but with the addition of compounds such as ethionin, D-norleucine or D-methionine to the medium for developing this actinomycete, which are antimetabolytes of methionine, the primary donor of methyl groups in microbiological synthesis of tetracycline molecules. Hydrogenolysis of the aforementioned 6-demethyltetracycline (32.3.11) with hydrogen using a palladium on carbon catalyst gives 4-dimethylamino-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo- 2-napthacencarboxamide (32.3.12), which is nitrated at position 9 by potassium nitrate in aqueous hydrofluoric acid, which forms the nitro compound (32.3.13). This is reduced to the corresponding amino derivative (32.3.14) by hydrogen over platinum dioxide. The resulting aminophenyl compound (32.3.14) is then nitrated with nitric acid in the presence of sulfuric acid to make 7-nitro-9-amino-4-naphthacencarboxamide (32.3.15).
    This undergoes diazotization when reacted with butylnitrate in sulfuric acid, and the resulting diazo derivative (32.3.16) is reduced with hydrogen using a palladium on carbon catalyst. During this, the product is deazotized, while the nitro group is simultaneously reduced to an amino group, which undergoes exhaustive methylation by formaldehyde into minocycline (32.3.17).

    Dosage forms

    Up to 200 mg daily in divided doses.

    Minocycline Preparation Products And Raw materials

    Raw materials

    Preparation Products


    Minocycline Suppliers

    Global( 127)Suppliers
    Supplier Tel Fax Email Country ProdList Advantage
    Henan DaKen Chemical CO.,LTD.
    +86-371-66670886
    info@dakenchem.com China 21022 58
    Henan Tianfu Chemical Co.,Ltd.
    0371-55170693
    0371-55170693 info@tianfuchem.com CHINA 22607 55
    ATK CHEMICAL COMPANY LIMITED
    +86 21 5161 9050/ 5187 7795
    +86 21 5161 9052/ 5187 7796 ivan@atkchemical.com CHINA 26734 60
    career henan chemical co
    +86-371-86658258
    sales@coreychem.com CHINA 29959 58
    Zhejiang ZETian Fine Chemicals Co. LTD
    18957127338
    stella@zetchem.com CHINA 2007 58
    Hebei Guanlang Biotechnology Co., Ltd.
    +8619930503282
    sales3@crovellbio.com China 5508 58
    Chongqing Chemdad Co., Ltd
    +86-13650506873
    sales@chemdad.com CHINA 37282 58
    CONIER CHEM AND PHARMA LIMITED
    86-18523575427
    sales@conier.com CHINA 47496 58
    Shaanxi Dideu Medichem Co. Ltd
    15319487004
    029-88380327 1015@dideu.com CHINA 4121 58
    Hefei TNJ Chemical Industry Co.,Ltd.
    0551-65418671
    0551-65418697 sales@tnjchem.com CHINA 37441 58

    View Lastest Price from Minocycline manufacturers

    Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
    2021-10-20 Minocycline
    10118-90-8
    US $10.00 / KG 100g 99% 1000MT/Month Wuhan wingroup Pharmaceutical Co., Ltd
    2021-08-31 Minocycline
    10118-90-8
    US $10.00 / Kg/Bag 1Kg/Bag 99%min 5000 Wuhan Monad Medicine Tech Co.,LTD
    2021-06-29 Minocycline USP/EP/BP
    10118-90-8
    US $1.10 / g 1g 99.9% 100 Tons Min Dideu Industries Group Limited

    10118-90-8(Minocycline)Related Search:


    • 12,12a-tetrahydroxy-1,11-dioxo--10
    • 2-naphthacenecarboxamide,4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro
    • -3,10,12,12a-tetrahydroxy-1,11,-dioxo-,(4s-(4alpha,4aalpha,5aalpha,12aalpha))
    • 7-dimethylamino-6-demethyl-6-deoxytetracycline
    • cl59806
    • [4s-(4alpha,4aalpha,5aalpha,12aalpha)]-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxonaphthacene-2-carboxamide monohydrochloride
    • (2e,4s,4ar,5as,12ar)-2-(amino-hydroxy-methylidene)-4,7-bis(dimethylamino)-10,11,12a-trihydroxy-4a,5,5a,6-tetrahydro-4h-tetracene-1,3,12-trione
    • minocyclin
    • 7-DIMETHYLAMINO-6-DEMETHYL-6-DEOXYTETRACYCLINE HYDROCHLORIDE
    • 7-DIMETHYLAMINO-6-DEMETHYL-6-DEOXYTETRACYCLINE, HCL
    • MYNOCINE
    • MINOCIN
    • MINOCYCLINE
    • MINOCYCLINE HCL
    • MinocyclineBase
    • Minocycline Hcl 13614-98-7 / Base
    • 2-Naphthacenecarboxamide, 4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo- (8CI)
    • 2-Naphthacenecarboxamide, 4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-, (4S,4aS,5aR,12aS)- (9CI)
    • 2-Naphthacenecarboxamide, 4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-, [4S-(4a,4aa,5aa,12aa)]-
    • (4S,4aS,5aR,12aS)-4,7-Bis(dimethylamino)-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
    • (4S)-4β,7-Bis(dimethylamino)-1,4,4aβ,5,5aβ,6,11,12a-octahydro-3,10,12,12aβ-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide
    • CS-588
    • 4β,7-Bis(dimethylamino)-1,4,4aβ,5,5aβ,6,11,12a-octahydro-3,10,12,12aβ-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide
    • Minocycline hydrochlorid
    • 7-DiMethylaMino-6-deMethyl-6-deoxytetracycline, CL 59806, Minocyclin
    • Minocycline dihydrochloride
    • Tigecycline Impurity 32
    • 2-Naphthacenecarboxamide, 4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-, (4S,4aS,5aR,12aS)-
    • (4S,4As,5ar,12as)-4,7-bis(dimethylamino)-3,10,12,12a-tetrahydroxy-1,11-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide dihydrochloride
    • Minocycline USP/EP/BP
    • 10118-90-8
    • C23H27N3O72ClH
    • Antibiotics
    • Antibiotics G-M
    • Antibiotics A to Z
    • BioChemical
    Copyright 2017 ? ChemicalBook. All rights reserved