CAS: 511-12-6; Dihydroergotamine

该化合物是主要用于治疗偏头痛和集束头痛的脑浆液浆的半合成衍生物,主要用于治疗偏头痛和类头痛,它作为血管抑制器,针对血清素受体,特别是5-HT1B和5-HT1D子型,通过缩小脑中膨胀的血管来帮助缓解头痛症状,该化合物通常通过内盘或静脉注射途径进行,以便迅速采取行动.二氢甲胺的特点是其结构复杂,包括四环系统和各种功能组,有助于其药理活动.众所周知,它的潜在副作用,包括腹泻,头晕,以及罕见的更严重的心血管问题.由于其血管抑制性,因此建议对心血管疾病患者谨慎行事.

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上下游产品

ergotamineH-ergotamane-2,18,3',6'-tetraone5'α-benzyl-3,12'-dihydroxy-2'-methyl-(3β,10α)-9,10-dihydro-3H-ergotamane-2,18,3',6'-tetraone (6aR,9R,10aR)-7-Cyano-4,6,6a,7,8,9,10,10a-°Ctahydro-indolo[4,3-fg]quinoline-9-carboxylic acid ((2R,5S,10aS,10bS)-5-benzyl-10b-hydroxy-2-methyl-3,6-dioxo-°Ctahydro-oxazolo[3,2-a]pyrrolo[2,1-c]pyrazin-2-yl)-amide 2-bromo-9,10-dihydro-α-ergotamine 6-demethyl-9,10-dihydroergotamine

合成工艺路线路线简述

  • 合成目标产物 Dihydroergotamine 主要起始原料 Ergotamine
  • (文献来源)合成步骤主要原料 Ergotamine
📜麦角胺置于镍 甲醇体系中,用 1,4-二氧六环 作为反应溶剂,以81%的收率获得产物双氢麦角胺
参考文献:Mayer; Eich,Pharmazie,1984,Vol. 39,# 8,P. 537-538
标题:Mayer; Eich,Pharmazie,1984,Vol. 39,# 8,P. 537-538

海关参考信息

专利信息


专利号:US-4818816-A
优先权日:1981-04-28
标 题:Process for the organic synthesis of oligosaccharides and derivatives thereof
发明人:PETITOU MAURICE; JACQUINET JEAN-CLAUDE; SINAY PIERRE; CHOAY JEAN; LORMEAU JEAN-CLAUDE; NASSR MAHMOUD
权利人:CHOAY SA
摘要:The invention relates to a process for the organic synthesis of oligosaccharides constituting or comprising fragments of acid mucopolysaccharides comprising the reaction of two compounds constituted or terminated by units of glucosamine structure and of uronic acid structure respectively, said units being specifically substituted. This process particularly enables valuable anticoagulant drugs to be obtained.

专利号:US-4943630-A
优先权日:1982-10-27
标题 :Method for carrying out the organic synthesis of oligosaccharides containing galactosamine-uronic acid patterns, new oligosaccharides obtained and biological applications thereof
发明人:JACQUINET JEAN-CLAUDE; PETITOU MAURICE; SINAY PIERRE; CHOAY JEAN
权利人:CHOAY SA
摘要:Process for the organic synthesis of oligosaccharides forming or corresponding to fragments of acid mucopolysaccharides wherein two compounds comprised of or terminated respectively by patterns of galactosamine structure and patterns of uronic acid structure. Said patterns are specifically substituted. Said process results in oligosaccharides usable particularly in therapy.

专利号:US-7459443-B2
优先权日:1999-04-08
标 题 :Synthesis of biologically active compounds in cells
发明人:SERGEEV PAVEL
权利人:SERGEEV PAVEL
摘要:This invention relates to a new method of synthesis of biologically active substances of determined structure directly in the cells of living organisms containing specific RNA or DNA molecules of determined sequence. The method is based on the hybridization of two or more oligomers bound with biologically inactive precursors of biologically active substances to specific RNA or DNA in vivo in the cells of living organisms. After hybridization of the oligomers to RNA or DNA the biologically inactive precursors bound to the 5′ and/or 3′ ends of the oligomers can interact with each other to make biologically active form of the substances. This changing of properties is due to chemical reactions which bind the biologically inactive precursors through a chemical bond into a biologically active form of the whole compound.

专利号:US-11311505-B2
优先权日:2017-02-24
标 题:Synergistic compositions to stimulate the synthesis of human lung and sinus surfactants to decrease coughing, increase FEV-1/FVC ratios, decrease lung fibrosis, by increasing apoptosis of myofibroblasts
发明人:MARTIN ALAIN
权利人:MARTIN ALAIN; CELLULAR SCIENCES INC
摘要:Methods for the treatment of patients with both Chronic Obstructive Pulmonary Disease (COPD) and pulmonary fibrosis, and of patients with idiopathic pulmonary fibrosis without COPD, by stimulating the synthesis of human and animal patient lung and sinus surfactants to increase lung functions, inhibiting fibrosis and reducing coughing and nasal erythema, include the following steps: A) analyzing and diagnosing a patient with a lung ailment selected from the group consisting of i) both COPD and pulmonary fibrosis; and ii) idiopathic pulmonary fibrosis without COPD; and, B) treating the patient to raise the patient's lung functions including FEV1/FVC ratio by contacting mammalian cells with a [therapeutically effective amount of a treatment] composition that includes: a) a pyruvate salt; b) a phosphate; c) a salt of calcium; and d) a salt of magnesium, in an aqueous carrier, containing no more than 2.2 grams of said pyruvate salt per liter.

专利号:US-10813893-B2
优先权日:2017-02-24
标 题:Compositions and methods for the treatment and prevention of chronic hypoxemia and dyspnea
发明人:MARTIN ALAIN
权利人:MARTIN ALAIN; CELLULAR SCIENCES INC
摘要:The present invention has shown that not all salts of pyruvic acid enhance lung functions or enhance the synthesis of lung surfactants and that certain salts of pyruvic acid with the correct concentrations of calcium, phosphate and magnesium, are synergistic in their ability to enhance the synthesis of lung surfactants that will enhance lung alveoli functions, while decreasing coughing and lung tightness, and increasing oxygen saturation values to prevent hypoxemia. This patent demonstrates that the sodium pyruvate formula with calcium, phosphate and magnesium was superior over standard sodium pyruvate formula in saline alone in the removal of mucus, reduction of lung or sinus infections, and in reducing drug side effects and congestion. The use of this formula clearly demonstrated that it can be used to produce better efficacy in patients with hypoxemia, with lung and sinus diseases including, asthma, COPD, cystic fibrosis, interstitial lung disease, allergic rhinitis, sinusitis, Alzheimer's, disease, Parkinson's disease, brain trauma, nicotine addiction, sleep apnea, autism, migraine headaches, sleep disorders, lung and sinus infections, cancer therapy with cancer drugs, nicotine addiction, and medications that cause a decrease in lung surfactants.

专利号:US-11628186-B2
优先权日:2017-02-24
标题 :Method and composition for the reduction of viral replication, duration and spread of the COVID-19 and the flu
发明人:MARTIN ALAIN
权利人:MARTIN ALAIN; CELLULAR SCIENCES INC
摘要:A method for stimulating the synthesis of nasal nitric oxide and nasal and lung surfactants to inhibit the docking and adhesion of viruses to cellular receptors, including ACE2, to reduce viral replication, duration, spread and severity of infections, and also to inhibit lung fibrosis, increase the synthesis of serotonin to reduce coughing and mouth breathing, reduce the cytokine storm produced by LI-6 caused by viruses such as COVID-19 and flu in patients susceptible to these infections, including patients with hypoxemia, asthma, chronic obstructive pulmonary disease, cystic fibrosis, diabetics, interstitial lung disease, pulmonary fibrosis, allergic rhinitis, sinusitis, smokers, sleep apnea and lung cancer, which includes: contacting mammalian cells with a therapeutically effective amount of a composition, said composition including the following constituents: sodium pyruvate; a phosphate; a salt of calcium; and a salt of magnesium.

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主要参考文献


1: Tfelt-Hansen PC, Diener HC. Use of dihydroergotamine (DHE) should be restricted to no more than twice a week. Headache. 2014 Oct;54(9):1523-5. doi: 10.1111/head.12389. Epub 2014 May 26. Review. doi: 10.1212/WNL.0b013e3182377dbb. Epub 2011 Nov 2. doi: 10.1007/s40263-013-0061-2. Review. doi: 10.1111/head.12269. doi: 10.1111/head.12184. Review. doi: 10.1089/jamp.2012.0999. Epub 2012 Dec 28. doi: 10.1177/0333102415570495. Epub 2015 Feb 9. doi: 10.1177/0333102413483372. Epub 2013 Apr 15. Review. doi: 10.2147/DDDT.S44093. Print 2013.
10: Eller M, Gelfand AA, Riggins NY, Shiboski S, Schankin C, Goadsby PJ. Exacerbation of headache during dihydroergotamine for chronic migraine does not alter outcome. Neurology. 2016 Mar 1;86(9):856-9. doi: 10.1212/WNL.0000000000002406. Epub 2016 Feb 3.
11: Marichal-Cancino BA, González-Hernández A, Manrique-Maldonado G, Ruiz-Salinas II, Altamirano-Espinoza AH, MaassenVanDenBrink A, Villalón CM. Intrathecal dihydroergotamine inhibits capsaicin-induced vasodilatation in the canine external carotid circulation via GR127935- and rauwolscine-sensitive receptors. Eur J Pharmacol. 2012 Oct 5;692(1-3):69-77. doi: 10.1016/j.ejphar.2012.07.033. Epub 2012 Jul 27. Epub 2016 Aug 2. Epub 2016 Sep 14.

合成参考文献


参考文献:10.1016/j.ajem.2009.05.021
摘要:Acikel S, Dogan M, Sari M, Kilic H, Akdemir R. Prinzmetal-variant angina in a patient using zolmitriptan and citalopram. The American Journal of Emergency Medicine. 2010 Feb;28(2):257.e3–6. doi: 10.1016/j.ajem.2009.05.021.
参考文献:10.1007/s00228-011-1084-6
摘要:Arbouw MEL, Movig KLL, Guchelaar H, Neef C, Egberts TCG. Dopamine agonists and ischemic complications in Parkinson’s disease: a nested case–control study. European Journal of Clinical Pharmacology. 2011 Jul 22;68(1):83–8. doi: 10.1007/s00228-011-1084-6.
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