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| 化学名: | ミノサイクリン·塩酸塩 | | 英語化学名: | Minocycline hydrochloride | | 别名: | KlinoMycin, Minocycline chloride, MinoMycin, NSC 141993;(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 hydrochloride;2-Naphthacenecarboxamide, 4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-, hydrochloride (1:1), (4S,4aS,5aR,12aS)-;Minocycline hydrochloride Solution, 100ppm;Minocycline hydrochloride, >=98%;[4S-(4alpha,4aalpha,5aalpha,12aalpha)]-4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-te;10,12,12a-tetrahydroxy-1,11-dioxo--monohydrochloride;2-(Amino-hydroxy-methylidene)-4,7-bis(dimethylamino)-10,11,12a-trihydroxy-4,4a,5,5a,6,12a-hexahydrotetracene-1,3,12-trione hydrochloride | | CAS番号: | 13614-98-7 | | 分子式: | C23H28ClN3O7 | | 分子量: | 493.94 | | EINECS: | 237-099-7 | | カテゴリ情報: | DAYPRO;antibiotic;API;Antibiotic Explorer;Intermediates & Fine Chemicals;Pharmaceuticals;Peptide Synthesis/Antibiotics;Antibacterial;13614-98-7 | | Mol File: | 13614-98-7.mol |  |
| 融点 | 205-210° (dec) | | 沸点 | 813℃ | | 闪点 | >110°(230°F) | | 貯蔵温度 | 2-8°C | | 溶解性 | Sparingly soluble in water, slightly soluble in ethanol (96 per cent). It dissolves in solutions of alkali hydroxides and carbonates. | | 外見 | crystalline | | 色 | yellow | | 水溶解度 | Freely soluble in water | | Merck | 14,6202 | | 安定性： | Light Sensitive | | InChIKey | GLMUAFMGXXHGLU-VQAITOIOSA-N | | SMILES | [C@@]12([H])C[C@@]3([H])C(C(=O)C4C(O)=CC=C(N(C)C)C=4C3)=C(O)[C@]1(O)C(=O)C(C(=O)N)=C(O)[C@H]2N(C)C.Cl |&1:0,3,21,31,r| | | LogP | 0.808 (est) | | CAS データベース | 13614-98-7(CAS DataBase Reference) |
| 主な危険性 | Xi | | Rフレーズ | 36/37/38 | | Sフレーズ | 26-36 | | RIDADR | 3249 | | WGK Germany | 3 | | RTECS 番号 | QI7630500 | | 国連危険物分類 | 6.1(b) | | 容器等級 | III | | HSコード | 29413020 | | 毒性 | human,TDLo,oral,14286ug/kg/10 (14.286mg/kg),LUNGS, THORAX, OR RESPIRATION: RESPIRATORY OBSTRUCTIONLUNGS, THORAX, OR RESPIRATION: DYSPNEASKIN AND APPENDAGES (SKIN): "DERMATITIS, OTHER: AFTER SYSTEMIC EXPOSURE",Archives of Internal Medicine. Vol. 154, Pg. 1633, 1994. |
| | ミノサイクリン·塩酸塩 Usage And Synthesis |
| 外観 | うすい黄色～褐黄色、結晶～粉末 | | 溶解性 | メタノールにやや溶けやすく、水にやや溶けにくい。 | | 用途 | テトラサイクリン系抗生物質
です。細菌の 30S リボソームに結合し、ア
ミノアシル -tRNA のリボソーム上の A 部位
への結合を阻害します。抗菌スペクトルは広
く、マイコプラズマ、クラミジアなどにも抗
菌作用を示します。 | | 用途 | テトラサイクリン系抗生物質
です。細菌の 30S リボソームに結合し、ア
ミノアシル -tRNA のリボソーム上の A 部位
への結合を阻害作用を示します。抗菌スペク
トルは広く、マイコプラズマ、クラミジア等
にも抗菌作用を示します。 | | 効能 | 抗生物質, タンパク質合成阻害薬 | | 商品名 | ペリオクリン (サンスター); ミノサイクリン塩酸塩 (沢井製薬); ミノマイシン (ファイザー); ミノマイシン (ファイザー); ミノマイシン (ファイザー); ミノマイシン (ファイザー) | | 説明 | Minocycline HCl (13614-98-7) displays antiapoptotic, anti-inflammatory1 activity. Prevents neuropathic pain in a rat sciatic nerve injury model.1 Reduces MMP-9 activity.2 Attenuates disease severity in mouse models of multiple sclerosis.3 Displays neuroprotective activity.4 Minocycline HCl may be effective in methotrexate-induced lung fibrosis.5?Orally active and brain penetrant. | | 化学的特性 | Yellow Crystalline Powder | | Originator | Minocin,Lederle ,US,1971 | | 使用 | antiinflammatory | | 使用 | Second generation tetracycline antibiotic. Antibacterial. | | 使用 | Minocycline hydrochloride is a salt prepared from minocycline, taking advantage of the two basic dimethylamino groups which protonate and readily form a salt from hydrochloric acid solutions. The hydrochloride is the preferred formulation for pharmaceutical 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. | | 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). | | Therapeutic Function | Antibiotic | | 一般的な説明 | Minocycline, 7-dimethylamino-6-demethyl-6-deoxytetracycline(Minocin, Vectrin), the most potent tetracycline currentlyused in therapy, is obtained by reductive methylationof 7-nitro-6-demethyl-6-deoxytetracycline. It was releasedfor use in the United States in 1971. Because minocycline,like doxycycline, lacks the 6-hydroxyl group, it is stablein acids and does not dehydrate or rearrange to anhydroor lactone forms. Minocycline is well absorbed orally togive high plasma and tissue levels. It has a very long serumhalf-life, resulting from slow urinary excretion and moderateprotein binding. Doxycycline and minocycline, alongwith oxytetracycline, show the least in vitro calcium bindingof the clinically available tetracyclines. The improved distributionproperties of the 6-deoxytetracyclines have been attributedto greater lipid solubility.
Perhaps the most outstanding property of minocyclineis its activity toward Gram-positive bacteria, especiallystaphylococci and streptococci. In fact, minocycline hasbeen effective against staphylococcal strains that are resistantto methicillin and all other tetracyclines, includingdoxycycline. Although it is doubtful that minocyclinewill replace bactericidal agents for the treatment of lifethreateningstaphylococcal infections, it may become auseful alternative for the treatment of less serious tissueinfections. Minocycline has been recommended for thetreatment of chronic bronchitis and other upper respiratorytract infections. Despite its relatively low renal clearance,partially compensated for by high serum and tissuelevels, it has been recommended for the treatment of urinary tract infections. It has been effective in the eradicationof N. meningitidis in asymptomatic carriers. | | Biochem/physiol Actions | Minocycline is a broad spectrum antibiotic with bacteriostatic function. Minocycline has anti-inflammatory properties. Minocycline inhibits lipopolysaccharide mediated inflammatory cytokine tumour necrosis factor (TNF-α) secretion by macrophages. Minocycline inhibits macrophage proliferation in a dose dependent manner. Minocycline inhibits neuroinflammation in pre-plaque of Alzheimer′s disease-like amyloid pathology through inhibition of key inflammatory enzymes like inducible nitric oxide synthase (iNOS), matrix metalloproteinase 9 (MMP-9) and 5-lipoxygenase. Minocycline inhibits endothelial cell proliferation and angiogenesis. Minocycline exhibits anti-tumor activity in glioma by inhibiting membrane type 1 matrix metalloproteinase (MT1-MMP). Minocycline increases cognition and neuronal differentiation. zMinocycline effectively reduces neuropathic pain by increasing the functions of nociceptin/orphanin FQ. | | 副作用 | Common side effects of Minocycline hydrochloride include: nausea, vomiting, diarrhoea, dizziness, lightheadedness or spinning sensation. Individuals may experience symptoms of serious adverse reactions such as gingival hyperpigmentation, pain/difficulty swallowing, tinnitus or hearing loss, joint stiffness/pain/swelling, nephrotoxicity (elevated urea nitrogen, interstitial nephritis), hepatotoxicity (hyperbilirubinaemia, hepatic cholestasis, elevated liver enzymes, fatal hepatic failure, and jaundice), and hypersensitivity reactions. It rarely causes elevated pressure around the brain (intracranial hypertension - IH). The risk of this side effect is greater in women of childbearing age who are overweight or who have had IH in the past. Serious intestinal disorders including: non-stop diarrhoea, abdominal or stomach pain/cramps, and blood/mucus in the stool are less common. | | Veterinary Drugs and Treatments | Minocycline may be useful for treating Brucellosis (in combination
with aminoglycosides), Lyme disease,
and certain nosocomial infections
where other more commonly used drugs are ineffective.
It has been investigated as adjunctive therapy for treating hemangiosarcomas,
but early results have been disappointing. | | 貯蔵 | +4°C | | 参考文献 | 1) Padi and Kulkarni (2008), Minocycline prevents the development of neuropathic pain, but not acute pain: possible anti-inflammatory and antioxidant mechanisms; Eur. J. Pharmacol., 601 79
2) Dziembowska et al. (2013), High MMP-9 activity levels in fragile X syndrome are lowered by minocycline; Am. J. Med. Genet. A, 161A 1897
3) Brundula et al. (2002), Targeting leukocyte MMPs and transmigration: minocycline as a potential therapy for multiple sclerosis; Brain., 125 1297
4) Tikka et al. (2001), Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia; J. Neurosci., 21 2580
5) Kalemci et al. (2013), The efficacy of minocycline against methotrexate-induced pulmonary fibrosis in mice; Eur. Rev. Med. Pharmacol. Sci., 17 3334 |
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