甲基叔丁基醚置于甲烷磺酸体系中,化学反应生成 甲磺酸酚妥拉明 参考文献:Highly Pure Phentolamine Mesylate And Methods For Making Same 标题:Highly Pure Phentolamine Mesylate And Methods For Making Same 摘要:This Invention Provides Methods For Synthesizing Phentolamine Mesylate From Phentolamine And Methanesulfonic Acid In The Presence Of Acetone And Water. The Methods Of The Present Invention Provide Highly Pure Phentolamine Mesylate. The Invention Also Provides Highly Pure Phentolamine Mesylate.
专利号:US-5746982-A 优先权日:1996-02-29 标题 :Apparatus for automated synthesis of chemical compounds 发明人:SANEII HOSSAIN; BOROOMAND MOHAMMAD R; FERRIELL MICHAEL R 权利人:ADVANCED CHEMTECH INC 摘要:Apparatus for the synthesis of chemical compounds consists of a housing having a top, front, side and rear walls surrounding and enclosing a reaction table. A track on the rear wall of the housing carries a pair of extending arms on each of which is movably mounted a vertically extendible probe for positioning at various locations over the reaction table. At least on control syringe communicates between the probe and containers for system fluids. A programmable controller is provided for control of the syringe and probes. A reaction block on the reaction table consists of a body having an upper portion and a lower portion and an upper and lower surface and a multiplicity of reaction wells for carrying out the synthesis. Each reaction well is closed at its lower end and open to the upper surface. A flushing conduit is located adjacent each of the well and is in fluid communication with the closed lower end of the reaction well. A manifold section is in fluid communication with the flushing conduit for leading fluid into and out of the body responsive to the creation of a pressure differential between the reaction well and the manifold section. The pressure in the reaction well is greater than that in the manifold section during the flushing of the well. A heating and cooling module may be attached to the reaction block for controlling the temperature of the reaction wells.
专利号:US-2003050305-A1 优先权日:2000-05-22 标题:Thromboxane inhibitors, compositions and methods of use 发明人:TEJADA INIGO SAENZ DE 摘要:The present invention describes methods for treating or preventing sexual dysfunctions in males and females, and for enhancing sexual responses in males and females by administering a therapeutically effective amount of at least one thromboxane inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The male or female may preferably be diabetic. The present invention also provides novel compositions comprising at least one thromboxane inhibitor, and, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and, optionally, at least one therapeutic agent, such as, vasoactive agents, nonsteroidal antiinflanmmatory compounds (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, anticoagulants, angiotensin converting enzymes (ACE) inhibitors, angiotensin II receptor antagonists, renin inhibitors, and mixtures thereof. The present invention also provides methods for treating or preventing ischemic heart disorders, myocardial infarction, angina pectoris, stroke, migraine, cerebral hemorrhage, cardiac fatalities, transient ischaemic attacks, complications following organ transplants, coronary artery bypasses, angioplasty, endarterectomy, atherosclerosis, pulmonary embolism, bronchial asthma, bronchitis, pneumonia, circulatory shock of various organs, nephritis, graft rejection, cancerous metastases, pregnancy-induced hypertension, preeclampsia, eclampsia, thrombotic and thromboembolic disorders, intrauterine growth, gastrointestinal disorders, renal diseases and disorders, disorders resulting from elevated uric acid levels and dysmenorrhea, and for inhibiting platelet aggregation or platelet adhesion or relaxing smooth muscles.
专利号:US-7238814-B2 优先权日:2000-05-09 标题:Compositions of S-nitrosothiols and methods of use 发明人:MAREK PRZEMYSLAW A; TROCHA ANDZREJ M; LIN CHIA-EN; RANATUNGE RAMANI R; RICHARDSON STEWART K 权利人:NITROMED INC 摘要:The invention describes compositions and kits comprising 4-aza-4-(2-methyl-2-sulfanylpropyl) tricyclo(5.2.1.0<2,6>)dec-8-ene-3,5-dione; 4-aza-4-(2-methyl-2-(nitrosothio)propyl) tricyclo(5.2.1.0<2,6>)dec-8-ene-3,5-dione; 4-{1-methyl-1-((2,4,6-trimethoxyphenyl)methylthio)ethyl}-1,3-oxazolidin-2-one; 2-aAmino-3-methyl-3-((2,4,6-trimethoxyphenyl)methylthio)butan-1-ol; 4-(1-methyl-1-(nitrosothio)ethyl)-1,3-oxazolidin-2-one; or pharmaceutically acceptable salts thereof. The compositions of the invention can further comprise at least one penetration enhancer, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one vasoactive agent.
专利号:WO-0054773-A1 优先权日:1999-03-12 标题:Dopamine agonists in combination with nitric oxide donors, compositions and methods of use 发明人:GARVEY DAVID S 权利人:NITROMED INC; GARVEY DAVID S 摘要:The present invention is directed to novel compositions comprising at least one dopamine agonist in combination with at least one nitric oxide donor (i.e. compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or are substrates for nitric oxide synthase). The novel compositions may optionally comprise at least one therapeutic agent, such as, a vasoactive agent, an antimetic agent, and mixtures thereof. The dopamine agonist is preferably apomorphine. The present invention is also directed to methods for treating and/or preventing sexual dysfunctions and/or enhancing sexual responses in patients. In other embodiments, the present invention is directed to methods treating or preventing neurodegenerative diseases, mitochondrial diseases, spinal cord injury, central or psychostimulant addiction, senile dementia, circulatory disorders, cardiovascular disorders, hyperprolactinaemia or myopia. The compounds and/or compositions of the present invention can also be provided in the form of a pharmaceutical kit.
专利号:US-6187756-B1 优先权日:1996-09-05 标 题 :Composition and methods for treatment of neurological disorders and neurodegenerative diseases 发明人:LEE ROBERT K K; WURTMAN RICHARD J 权利人:MASSACHUSETTS INST TECHNOLOGY 摘要:It has been discovered that the stimulation of β-adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising β-adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by β-adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E 2 (PG E 2 ), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of β-adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E 2 , forskolin, or nicotine ditartrate is inhibited by immunosuppressants or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium/calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.
专利号:US-6469055-B2 优先权日:1996-09-05 标题 :Compositions and methods for treatment of neurological disorders and neurodegenerative diseases 发明人:LEE ROBERT K K; WURTMAN RICHARD J 权利人:MASSACHUSETTS INST TECHNOLOGY 摘要:It has been discovered that the stimulation of β-adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising β-adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by β-adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E 2 (PG E 2 ), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of β-adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E 2 , or forskolin is inhibited by immunosuppressants, immunophilin ligands, or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium/calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.
1: Prados-Frutos JC, Rojo R, González-Serrano J, González-Serrano C, Sammartino G, Martínez-González JM, Sánchez-Monescillo A. Phentolamine mesylate to reverse oral soft-tissue local anesthesia: A systematic review and meta-analysis. J Am Dent Assoc. 2015 Oct;146(10):751-9.e3. doi: 10.1016/j.adaj.2015.04.018. Review. doi: 10.4103/0970-4388.165646. doi: 10.4103/2279-042X.108371. 5: Yagiela JA. What's new with phentolamine mesylate: a reversal agent for local anaesthesia? SAAD Dig. 2011 Jan;27:3-7. Review. doi: 10.1016/j.cden.2010.06.004. Review. doi: 10.2344/0003-3006-56.4.123. 10: Tavares M, Goodson JM, Studen-Pavlovich D, Yagiela JA, Navalta LA, Rogy S, Rutherford B, Gordon S, Papas AS; Soft Tissue Anesthesia Reversal Group. Reversal of soft-tissue local anesthesia with phentolamine mesylate in pediatric patients. J Am Dent Assoc. 2008 Aug;139(8):1095-104. Erratum in: J Am Dent Assoc. 2008 Oct;139(10):1312. Long-term safety and efficacy of oral phentolamine mesylate (Vasomax) in men with mild to moderate erectile dysfunction. Int J Impot Res. 2002 Aug;14(4):266-70.
合成参考文献
参考文献:10.1007/s11916-011-0218-y 摘要:Jarrell J. Endometriosis and abdominal myofascial pain in adults and adolescents. Curr Pain Headache Rep. 2011 Oct;15(5):368–76. doi: 10.1007/s11916-011-0218-y. 参考文献:10.1007/s12028-011-9598-4 摘要:Bruder N, Rabinstein A; Participants in the International Multi-Disciplinary Consensus Conference on the Critical Care Management of Subarachnoid Hemorrhage. Cardiovascular and pulmonary complications of aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2011 Sep;15(2):257–69. doi: 10.1007/s12028-011-9598-4. 参考文献:10.1007/s00467-011-1964-0 摘要:Chandar J, Zilleruelo G. Hypertensive crisis in children. Pediatr Nephrol. 2012 May;27(5):741–51. doi: 10.1007/s00467-011-1964-0.