(2S,6'R)-7-chloro-2',4,6-trimethoxy-6'-methyl-3H-spiro[1-benzofuran-2,1'-cyclohexan]-2'-ene-3,4'-dione

• ChemBase编号: 283
• 分子式: C17H17ClO6
• 平均质量: 352.76628
• 单一同位素质量: 352.07136594
• SMILES: Clc1c2O[C@]3([C@@H](CC(=O)C=C3OC)C)C(=O)c2c(OC)cc1OC
• Canonical SMILES: COC1=CC(=O)C[C@H]([C@@]21Oc1c(C2=O)c(OC)cc(c1Cl)OC)C
• InChI: InChI=1S/C17H17ClO6/c1-8-5-9(19)6-12(23-4)17(8)16(20)13-10(21-2)7-11(22-3)14(18)15(13)24-17/h6-8H,5H2,1-4H3/t8-,17+/m1/s1
• InChIKey: DDUHZTYCFQRHIY-RBHXEPJQSA-N

名称和登记号

名称

• IUPAC标准名: (2S,6'R)-7-chloro-2',4,6-trimethoxy-6'-methyl-3H-spiro[1-benzofuran-2,1'-cyclohexan]-2'-ene-3,4'-dione
• IUPAC传统名: griseofulvin; (2S,6'R)-7-chloro-2',4,6-trimethoxy-6'-methyl-3H-spiro[1-benzofuran-2,1'-cyclohexan]-2'-ene-3,4'-dione
• 商标名: Amudane; Biogrisin-fp; Curling factor; Delmofulvina; Fulcin; Fulcine; Fulvican grisactin; Fulvicin; Fulvicin P/G; Fulvicin U/F; Fulvicin-P/G; Fulvicin-U/F; Fulvina; Fulvinil; Fulvistatin; Fungivin; Greosin; Gresfeed; Gricin; Grifulin; Grifulvin; Grifulvin V; Gris-PEG; Grisactin; Grisactin Ultra; Griscofulvin; Grisefuline; Griseo; Griseofulvin forte; Griseofulvin-forte; Griseomix; Grisetin; Grisofulvin; Grisovin; Grisovin FP; Grizeofulvin; Grysio; Guservin; Lamoryl; Likuden; Likunden; Murfulvin; Neo-Fulcin; Neocid; Poncyl; Spirofulvin; Sporostatin; Sporostatin xan; Xuanjing
• 别名: (2S)-反式-7-氯-2′,4,6-三甲氧基-6′-甲基螺(苯并呋喃-2[3H],1′-[2]环己烯)-3,4′-二酮; 灰黄霉素; (+)-灰黄霉素; 灰黄霉素; Griseofulvin; (+)-Griseofulvin; Griseofulvina [INN-Spanish]; Griseofulvine [INN-French]; Griseofulvinum [INN-Latin]; Griseofulvin; (2S)-trans-7-Chloro-2′,4,6-trimethoxy-6′-methylspiro(benzofuran-2[3H],1′-[2]cyclohexene)-3,4′-dione; Griseofulvin; (1'S,6'R)-7-chloro-2',4,6-trimethoxy-6'-methyl-3H-spiro[benzofuran-2,1'-cyclohex[2]ene]-3,4'-dione; Grisovin; Fulvicin; Curling factor; Gricin; Grifulvin; Grisactin; Norofulvin; Likuden; Idifulvin; (1'S,6'R)-7-Chloro-2',4,6-trimethoxy-6'-methyl-spiro[benzofuran-2(3H),1'-[2]cyclohexene]-3,4'-dione; Amudane; Fulcin; Grisovi; (+)-Griseofulvin; Spirofulvin; Sporostatin; Xuanjing; (2S,6'R)-7-chloro-2',4,6-trimethoxy-6'-methyl-3H-spiro[1-benzofuran-2,1'-cyclohexan]-2'-ene-3,4'-dione

登记号

• CAS号: 126-07-8
• EC号: 204-767-4
• MDL号: MFCD00082343
• Beilstein号: 95226
• 默克索引号: 144549
• PubChem SID: 24895185; 24869893; 24895099; 46508437; 160963746
• PubChem CID: 441140
• CHEBI ID: 27779
• ATC码: D01BA01; D01AA08
• CHEMBL: 562
• Chemspider ID: 389934
• DrugBank ID: DB00400
• KEGG ID: D00209
• 美国药典/FDA物质标识码: 32HRV3E3D5
• 维基百科标题: Griseofulvin
• Medline Plus: a682295

理论计算性质

JChem

• Acid pKa: 17.688671
• 质子受体: 6
• 质子供体: 0
• LogD (pH = 5.5): 2.1721375
• LogD (pH = 7.4): 2.1721375
• Log P: 2.1721375
• 摩尔折射率: 87.8459 cm^3
• 极化性: 33.75892 Å^3
• 极化表面积: 71.06 Å^2
• 可自由旋转的化学键: 3
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 2.71
• LOG S: -3.84
• 溶解度: 5.04e-02 g/l

分子性质

理化性质

• 溶解度: 8.64 mg/L; Acetone; Benzene; Ethanol; Ethyl Acetate; Methanol
• 外观: Crystalline Solid
• 熔点: 216-220 °C; 218 - 220°C; 218-220 °C(lit.); 218-220°C; 220°C
• 比旋光度: [α]17/D +370°, c = 1 in chloroform; [α]20/D +355±5°, c = 1% in DMF(lit.)
• 疏水性(logP): 2; 2.053

安全信息

• 保存条件: -20°C Freezer
• RTECS编号: WG9800000
• 欧盟危险性物质标志: 有毒(Toxic) (T)
• 德国WGK号: 3
• 危险公开号: 60-61-40-43; 61-40-43
• 安全公开号: 22-36/37/39-45; 53-45
• TSCA收录: 否
• GHS危险品标识: GHS07; GHS08
• GHS警示词: Danger
• GHS危险声明: H317-H351-H360; H360-H351-H317
• GHS警示性声明: P201-P280-P308 + P313; P261-P280-P302+P352-P321-P405-P501A
• 个人保护装置: Eyeshields, Faceshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges; Eyeshields, Faceshields, Gloves, type P2 (EN 143) respirator cartridges
• 保存温度: -20°C

药理学性质

• 给药途径: Oral
• 生物利用度: Highly variable (25 to 70%)
• 半衰期: 9-21 hours
• 代谢: Hepatic demethylation and glucuronidation
• 法定药品分级: POM (UK), ?-only (U.S.)
• 妊娠期药物分类: B3 (Australia), C (United States)
• 生物活性机理: Binds tightly to new keratin which becomes highly resistant to fungal invasions

产品相关信息

• 纯度: ≥95% (HPLC); 95%; 97%; 97.0-102.0%
• 级别: VETRANAL™, analytical standard
• 适用性: meets USP testing specifications
• 生物来源: from Penicillium griseofulvum; Metab. of Penicillium griseofulvum
• 应用领域: activity against: Trichophyton rubrum; Antifungal agent against; Epidermophyton floccosum.; Microsporum audouini; Microsporum canis; Microsporum gypseum; Trichophyton crateriform; Trichophyton gallinae; Trichophyton interdigitalis; Trichophyton megnini; Trichophyton mentagrophytes; Trichophyton schoenleini; Trichophyton sulphureum; Trichophyton tonsurans; Trichophyton verrucosum
• Empirical Formula (Hill Notation): C17H17ClO6

详细说明

DrugBank - DB00400

• Drug Groups: approved
• Description: An antifungal antibiotic. Griseofulvin may be given by mouth in the treatment of tinea infections. [PubChem]
• Indication: For the treatment of ringworm infections of the skin, hair, and nails, namely: tinea corporis, tinea pedis, tinea cruris, tinea barbae, cradle cap or other conditions caused by Trichophyton or Microsporum fungi.
• Pharmacology: Griseofulvin is a mycotoxic metabolic product of Penicillium spp. It was the first available oral agent for the treatment of dermatophytoses and has now been used for more than forty years. Griseofulvin is fungistatic with in vitro activity against various species of Microsporum Epidermophyton, and Trichophyton. It has no effect on bacteria or on other genera of fungi. Following oral administration, griseofulvin is deposited in the keratin precursor cells and has a greater affinity for diseased tissue. The drug is tightly bound to the new keratin which becomes highly resistant to fungal invasions. Once the keratin-Griseofulvin complex reaches the skin site of action, it binds to fungal microtubules (tubulin) thus altering fungal mitosis.
• Toxicity: Side effects are minor: headaches, gastrointestinal reactions and cutaneous eruptions
• Affected Organisms: Yeast and other Trichophyton or Microsporum fungi
• Biotransformation: Primarily hepatic with major metabolites being 6-methyl-griseofulvin and its glucuronide conjugate.
• Absorption: Poorly absorbed from GI ranging from 25 to 70% of an oral dose. Absorption is significantly enhanced by administration with or after a fatty meal.
• Half Life: 9-21 hours
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Sigma Aldrich - G4753

Biochem/physiol Actions
Antifungal. Mode of action: Disrupts the mitotic spindle structure and inhibits nuclear division.1 Induces apoptosis in human tumor cell lines.2
包装
5, 25, 50 g in poly bottle

Sigma Aldrich - 856444

Features and Benefits
抗有丝分裂。

Sigma Aldrich - 46309

法律信息
VETRANAL 商标 Sigma-Aldrich Co. LLC

Sigma Aldrich - G2664

Biochem/physiol Actions
Griseofulvin disrupts microtubule assembly and mitotic spindle stucture possibly via tubulin aggregation.

Toronto Research Chemicals - G787500

It is an antifungal drug. It is used both in animal and in humans, to treat rigworm infections of the skin and nails. It is derived from the mold Penicillium griseofulvum.

参考文献

• Oxford, et al.: Biochem. J., 33, 240 (1939)
• Townley, E.R., et al.: Anal. Profiles Drug Subs., 8, 219 (1939)
• Aldrich Library of FT-IR Spectra, 1st edn., 1985, 2, 321D, (ir)
• Aldrich Library of 13C and 1H FT NMR Spectra, 1992, 2, 1309B, (nmr)
• Grove, J.F. et al., J.C.S., 1952, 3949; 3967, (struct, abs config)
• MacMillan, J., J.C.S., 1953, 1697, (deriv)
• McMaster, W.J. et al., J.C.S., 1960, 4628, (Dehydrogriseofulvin, Dechlorogriseofulvic acid)
• Stork, G. et al., J.A.C.S., 1962, 84, 310; 1964, 86, 471, (synth, ir, uv, nmr)
• Brown, W.A.C. et al., J.C.S., 1963, 1050, (cryst struct)
• Levine, S.G. et al., Tet. Lett., 1971, 311, (pmr, conformn)
• Levine, S.G. et al., J.O.C., 1975, 40, 2540, (cmr)
• IARC Monog., 1976, 10, 153; Suppl. 7, 391, (rev, tox)
• Kingston, D.G.I. et al., Phytochemistry, 1976, 15, 1037, (deriv)
• Sato, Y. et al., Tet. Lett., 1976, 3971, (cmr, biosynth)
• Malmros, G. et al., Cryst. Struct. Commun., 1977, 6, 463, (cryst struct)
• Townley, E.R., Anal. Profiles Drug Subst., 1979, 8, 219, (rev)
• Danishefsky, S. et al., J.A.C.S., 1979, 101, 7018, (synth)
• Hassan, M.A. et al., Anal. Profiles Drug Subst., 1980, 9, 583, (rev)
• Davies, R.R., Antifungal Chemother., 1980, 149, (rev, pharmacol, tox)
• Walker, F.J., Diss. Abstr. Int., B, 1982, 42, 4801, (synth)
• Puttaraja, N.K.A. et al., J. Crystallogr. Spectrosc. Res., 1982, 12, 415, (cryst struct)
• Oda, T. et al., Chem. Pharm. Bull., 1983, 31, 934, (synth, derivs)
• Itai, A. et al., Chem. Pharm. Bull., 1985, 33, 158, (isomer)
• Hussain, S.A., Diss. Abstr. Int., B, 1986, 47, 2394
• Negwer, M., Organic-Chemical Drugs and their Synonyms, 6th edn., Akademie-Verlag, 1987, 4313, (synonyms)
• Tomozane, H. et al., Chem. Pharm. Bull., 1990, 38, 925, (synth, bibl)
• Takeuchi, Y. et al., Chem. Pharm. Bull., 1991, 39, 3045, (synth)
• Pirrung, M.C. et al., J.A.C.S., 1991, 113, 8561, (synth)
• Kirk-Othmer Encycl. Chem. Technol., 4th edn., Wiley, 1991, 3, 483, (rev)
• Pesticide Manual, 9th edn., 1991, No. 6970
• Martindale, The Extra Pharmacopoeia, 30th edn., Pharmaceutical Press, 1993, 323
• Takeuchi, Y. et al., Chem. Pharm. Bull., 1997, 45, 327; 2011-2015, (synth)
• Cole, R.J. et al., Handbook of Toxic Fungal Metabolites, Academic Press, New York, 1981, 857; 862
• Lewis, R.J., Sax's Dangerous Properties of Industrial Materials, 8th edn., Van Nostrand Reinhold, 1992, GKE000