(4R,7R)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-4-methyl-5,8-dioxo-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.02,7.012,16]hexadeca-1(16),2,9,12,14-pentaene-4-carboxamide

• ChemBase编号: 578
• 分子式: C33H35N5O5
• 平均质量: 581.6615
• 单一同位素质量: 581.26381925
• SMILES: O1[C@]2(O)N([C@H](C(=O)N3[C@H]2CCC3)Cc2ccccc2)C(=O)[C@@]1(NC(=O)[C@H]1CN([C@H]2C(=C1)c1c3c(C2)c[nH]c3ccc1)C)C
• Canonical SMILES: O=C([C@H]1CN(C)[C@H]2C(=C1)c1cccc3c1c(C2)c[nH]3)N[C@]1(C)O[C@@]2(N(C1=O)[C@@H](Cc1ccccc1)C(=O)N1[C@H]2CCC1)O
• InChI: InChI=1S/C33H35N5O5/c1-32(35-29(39)21-15-23-22-10-6-11-24-28(22)20(17-34-24)16-25(23)36(2)18-21)31(41)38-26(14-19-8-4-3-5-9-19)30(40)37-13-7-12-27(37)33(38,42)43-32/h3-6,8-11,15,17,21,25-27,34,42H,7,12-14,16,18H2,1-2H3,(H,35,39)/t21-,25-,26+,27+,32-,33+/m1/s1
• InChIKey: XCGSFFUVFURLIX-VFGNJEKYSA-N

名称和登记号

名称

• IUPAC标准名: (4R,7R)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-4-methyl-5,8-dioxo-3-oxa-6,9-diazatricyclo[7.3.0.0^2,^6]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.0^2,^7.0^1^2,^1^6]hexadeca-1(16),2,9,12,14-pentaene-4-carboxamide; (4R,7R)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-4-methyl-5,8-dioxo-3-oxa-6,9-diazatricyclo[7.3.0.0^{2,6}]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(16),2,9,12,14-pentaene-4-carboxamide
• IUPAC传统名: ergomar; gynergen
• 商标名: Ergomar; Ergostat; Ergotamin; Ergoton-A; Medihaler Ergotamine; Wigrettes
• 别名: Ergotamine

登记号

• CAS号: 113-15-5
• PubChem SID: 46507632; 160964041
• PubChem CID: 8223
• CHEBI ID: 64318
• ATC码: N02CA02
• CHEMBL: 442
• Chemspider ID: 7930
• DrugBank ID: DB00696
• IUPHAR配体索引: 149
• KEGG ID: D07906
• 美国药典/FDA物质标识码: PR834Q503T
• 维基百科标题: Ergotamine

理论计算性质

JChem

• 极化性: 62.688698 Å^3
• 极化表面积: 118.21 Å^2
• 可自由旋转的化学键: 4
• 里宾斯基五规则: false
• Acid pKa: 9.695263
• 质子受体: 6
• 质子供体: 3
• LogD (pH = 5.5): 0.44161355
• LogD (pH = 7.4): 2.1667228
• Log P: 2.5976973
• 摩尔折射率: 160.1678 cm^3

ALOGPS 2.1

• 溶解度: 2.23e-01 g/l
• Log P: 2.95
• LOG S: -3.42

分子性质

理化性质

• 溶解度: Slight
• 疏水性(logP): 2

药理学性质

• 给药途径: Oral
• 生物利用度: Intravenous: 100%,; Intramuscular: 47%,; Oral: <1% (Enhanced by co-administration of caffeine )
• 排泄: 90% biliary
• 半衰期: 2 hours
• 代谢: Hepatic
• 法定药品分级: POM (UK); Rx-only (US); Schedule 4 (Australia)
• 妊娠期药物分类: X (US)

详细说明

DrugBank - DB00696

• Drug Groups: approved
• Description: A vasoconstrictor found in ergot of Central Europe. It is an alpha-1 selective adrenergic agonist and is commonly used in the treatment of migraine disorders. [PubChem]
• Indication: For use as therapy to abort or prevent vascular headache, e.g., migraine, migraine variants, or so called "histaminic cephalalgia".
• Pharmacology: Ergotamine is a vasoconstrictor and alpha adrenoreceptor antagonist. The pharmacological properties of ergotamine are extremely complex; some of its actions are unrelated to each other, and even mutually antagonistic. The drug has partial agonist and/or antagonist activity against tryptaminergic, dopaminergic and alpha adrenergic receptors depending upon their site, and it is a highly active uterine stimulant. It causes constriction of peripheral and cranial blood vessels and produces depression of central vasomotor centers. The pain of a migraine attack is believed to be due to greatly increased amplitude of pulsations in the cranial arteries, especially the meningeal branches of the external carotid artery. Ergotamine reduces extracranial blood flow, causes a decline in the amplitude of pulsation in the cranial arteries, and decreases hyperperfusion of the territory of the basilar artery. It does not reduce cerebral hemispheric blood flow.
• Toxicity: Signs of overexposure include irritation, nausea, vomiting, headache, diarrhea, thirst, coldness of skin, pruritus, weak pulse, numbness, tingling of extremities, and confusion.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Ergotamine is metabolized by the liver by largely undefined pathways, and 90% of the metabolites are excreted in the bile.
• Absorption: The bioavailability of sublingually administered ergotamine has not been determined.
• Half Life: 2 hours
• References: Tfelt-Hansen P, Saxena PR, Dahlof C, Pascual J, Lainez M, Henry P, Diener H, Schoenen J, Ferrari MD, Goadsby PJ: Ergotamine in the acute treatment of migraine: a review and European consensus. Brain. 2000 Jan;123 ( Pt 1):9-18. [Pubmed] ; Schardl CL, Panaccione DG, Tudzynski P: Ergot alkaloids--biology and molecular biology. Alkaloids Chem Biol. 2006;63:45-86. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

参考文献

• Tfelt-Hansen P, Saxena PR, Dahlof C, Pascual J, Lainez M, Henry P, Diener H, Schoenen J, Ferrari MD, Goadsby PJ: Ergotamine in the acute treatment of migraine: a review and European consensus. Brain. 2000 Jan;123 ( Pt 1):9-18. Pubmed
• Schardl CL, Panaccione DG, Tudzynski P: Ergot alkaloids--biology and molecular biology. Alkaloids Chem Biol. 2006;63:45-86. Pubmed