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131. 发明申请

US20050272781A1 Methods for the synthesis of pyridoxamine 有权
标题翻译：吡哆胺合成方法
公开(公告)号：US20050272781A1
公开(公告)日：2005-12-08
申请号：US11054527
申请日：2005-02-09
申请人： Raja Khalifah , Roland Keilitz , Christoph Koellner , Thorsten Degenhardt , Stephen Brand
发明人： Raja Khalifah , Roland Keilitz , Christoph Koellner , Thorsten Degenhardt , Stephen Brand
IPC分类号： A61K31/4415 , C07D213/62 , C07D213/66 , C07D213/67 , C07D401/12
CPC分类号： C07D213/66 , C07D213/67 , C07D401/06 , C07D401/12
摘要： The invention provides non-oxidative methods for the large scale manufacture of pyridoxamine (I) (4-aminomethyl-3-hydroxy-5-hydroxymethyl-2-methylpyridine): The invention also provides intermediate compounds for the synthesis of pyridoxamine, as well as compositions and methods for the treatment and/or prevention of conditions associated with the formation of post-Amadori advanced glycation end-products.
摘要翻译：本发明提供用于大规模生产吡哆胺（I）（4-氨基甲基-3-羟基-5-羟甲基-2-甲基吡啶）的非氧化方法：本发明还提供用于合成吡哆胺的中间体化合物，以及用于治疗和/或预防与后阿马多后期糖基化终产物形成相关的病症的组合物和方法。

132. 发明授权

US06890943B2 Pyridoxal analogues and methods of treatment 失效
标题翻译：吡哆醛类似物和治疗方法
公开(公告)号：US06890943B2
公开(公告)日：2005-05-10
申请号：US09863093
申请日：2001-05-22
申请人： Wasimul Haque
发明人： Wasimul Haque
IPC分类号： C07D491/048 , A61K31/44 , A61K31/443 , A61K45/00 , A61K45/06 , A61P3/02 , A61P7/00 , A61P7/04 , A61P9/00 , A61P9/04 , A61P9/06 , A61P9/10 , A61P9/12 , A61P35/00 , A61P43/00 , C07D213/66 , C07D491/04 , C07D213/30
CPC分类号： C07D213/66 , A61K31/44 , A61K45/06 , C07D491/04 , A61K2300/00
摘要： Pyridoxal analogues can be useful for treating B6 deficiency and related diseases; cardiovascular and related diseases; melanoma and related diseases; and symptoms thereof. One such analogue is a compound of the formula: or a pharmaceutically acceptable acid addition salt thereof, in which R1 is alkyl, alkenyl, in which alkyl or alkenyl can be interrupted by nitrogen, oxygen, or sulfur, and can be substituted at the terminal carbon by hydroxy, alkoxy, alkanoyloxy, alkanoyloxyaryl, alkoxyalkanoyl, alkoxycarbonyl, or dialkylcarbamoyloxy; alkoxy; dialkylamino; alkanoyloxy; alkanoyloxyaryl; alkoxyalkanoyl; alkoxycarbonyl; dialkylcarbamoyloxy; or aryl, aryloxy, arylthio, or aralkyl, in which aryl can be substituted by alkyl, alkoxy, amino, hydroxy, halo, nitro, or alkanoyloxy. These analogues can be administered, either alone or concurrently with known medications, to treat the above-described diseases.
摘要翻译：吡哆醛类似物可用于治疗B6缺陷及相关疾病; 心血管疾病及相关疾病; 黑素瘤及相关疾病; 及其症状。一种这样的类似物是下式的化合物或其药学上可接受的酸加成盐，其中R 1是烷基，烯基，其中烷基或烯基可以被氮，氧或硫中断并且可以在末端被羟基，烷氧基，烷酰氧基，烷酰氧基芳基，烷氧基烷酰基，烷氧基羰基或二烷基氨基甲酰氧基取代; 烷氧基二烷基氨基; 烷酰氧基; 烷酰氧基芳基烷氧基烷酰基烷氧基羰基二烷基氨基甲酰氧基或芳基，芳氧基，芳硫基或芳烷基，其中芳基可被烷基，烷氧基，氨基，羟基，卤素，硝基或烷酰氧基取代。这些类似物可以单独使用或与已知药物同时施用以治疗上述疾病。

133. 发明申请

US20040010015A1 Pyridoxine and pyridoxal analogues: new uses 失效
标题翻译：吡哆醇和吡哆醛类似物：新用途
公开(公告)号：US20040010015A1
公开(公告)日：2004-01-15
申请号：US10411552
申请日：2003-04-10
发明人： Wasimul Haque
IPC分类号： A61K031/4439 , A61K031/4415
CPC分类号： C07D401/06 , C07D213/40 , C07D213/48 , C07D213/66 , C07D401/12
摘要： The invention provides pyridoxal and pyridoxine analogues, pharmaceutical compositions containing pyridoxine and pyridoxal analogues, and methods of administering pharmaceutical compositions containing a therapeutically effective amount of at least one of these analogues. In accordance with the present invention, the pyridoxal and pyridoxine analogues can be used in the treatment or prevention of of heparin induced thrombocytopenia (HIT, stroke, and ischemia, and in the treatment of symptoms thereof. The the pyridoxal and pyridoxine analogues can be used in neuroprotection.
摘要翻译：本发明提供了吡哆醛和吡哆醛类似物，含有吡哆醛和吡哆醛类似物的药物组合物，以及施用含有治疗有效量的至少一种这些类似物的药物组合物的方法。根据本发明，吡哆醛和吡哆醛类似物可用于治疗或预防肝素诱导的血小板减少症（HIT，中风和局部缺血以及治疗其症状），吡哆醛和吡哆醛类似物可用于在神经保护。

134. 发明申请

US20030120074A1 Cardioprotective phosphonates and malonates 失效
公开(公告)号：US20030120074A1
公开(公告)日：2003-06-26
申请号：US10282328
申请日：2002-10-28
申请人： Medicure International Inc.
发明人： Wasimul Haque
IPC分类号： C07F009/58
CPC分类号： C07D213/66 , C07D213/65 , C07F9/58 , C07F9/6561
摘要： The present invention provides for pyridoxine phosphonate analogues such as, for example, ((2-methyl-3-hydroxy-4-hydroxymethyl-5-pyridyl)alkylphosphonates, and (2-methyl-3-hydroxy-4-hydroxymethyl-5-pyridyl)azaalkylphosphonates) and to pyridoxine malonate analogues, such as, for example, ((2-methyl-3-hydroxy-4-hydroxymethyl-5-pyridylmethyl)malonates), pharmaceutical compositions, and methods for treatment of cardiovascular and related diseases, and diabetes mellitus and related diseases.

135. 发明授权

US06228858B1 Advanced glycation end-product intermediaries and post-amadori inhibition 失效
标题翻译：高级糖基化终产物中间体和后阿马多利抑制
公开(公告)号：US06228858B1
公开(公告)日：2001-05-08
申请号：US08971285
申请日：1997-11-17
申请人： Billy G. Hudson , Parvin Todd , Raja Gabriel Khalifah , Aaron Ashley Booth
发明人： Billy G. Hudson , Parvin Todd , Raja Gabriel Khalifah , Aaron Ashley Booth
IPC分类号： A61K3150
CPC分类号： C07D213/66 , A61K31/00 , A61K31/04 , A61K31/435 , A61K31/44 , A61K31/4415 , A61K31/506 , A61K31/675 , A61K38/05 , A61K38/06 , A61K38/07 , C07C215/50 , C07K5/06034 , C07K5/06052 , C07K5/0812 , G01N33/68 , G01N33/6842 , G01N2400/02 , G01N2500/04
摘要： The instant invention provides compositions and methods for modeling post-Amadori AGE formation and the identification and characterization of effective inhibitors of post-Amadori AGE formation, and such identified inhibitor compositions.
摘要翻译：本发明提供了用于模拟阿马多前AGE形成的组合物和方法以及后Amadori AGE形成的有效抑制剂的鉴定和表征，以及这些鉴定的抑制剂组合物。

136. 发明授权

US6015821A Nicotinic acid esters and pharmaceutical compositions containing them 失效
标题翻译：烟酸酯和含有它们的药物组合物
公开(公告)号：US6015821A
公开(公告)日：2000-01-18
申请号：US952305
申请日：1998-03-03
申请人： David Frederick Horrobin , Mehar Manku , Austin McMordie , Philip Knowles , Peter Redden , Andrea Pitt
发明人： David Frederick Horrobin , Mehar Manku , Austin McMordie , Philip Knowles , Peter Redden , Andrea Pitt
IPC分类号： A61K31/44 , A61P3/06 , C07C69/007 , C07C69/587 , C07C69/76 , C07D209/28 , C07D213/30 , C07D213/66 , C07D213/79 , C07D213/80 , C07D233/94 , C07D279/36 , C07D321/00 , C07D339/04 , C07D499/00 , C07F9/09 , C07F9/655 , C07J1/00 , C07J5/00
CPC分类号： C07D213/30 , C07C69/007 , C07C69/587 , C07C69/76 , C07D209/28 , C07D213/66 , C07D213/80 , C07D233/94 , C07D279/36 , C07D321/00 , C07D339/04 , C07D499/00 , C07J1/0059 , C07J5/0053
摘要： Compounds, compositions, and methods of use as a pharmaceutical, where the compounds have structure (I), where B is --C(.dbd.O)-- or --CH.sub.2 --O--, C is a direct bond or is a diol residue, a hydroxy-substituted carboxylic acid residue, or a dicarboxylic acid residue, and D is a fatty acid residue or a fatty alcohol residue, where the acid residues or alcohol residues for ester linkages with the corresponding alcohols or acids.
摘要翻译： PCT No.PCT / GB96 / 01054 Sec。 371日期1998年3月3日 102（e）1998年3月3日PCT PCT 1996年5月1日PCT公布。公开号WO96 / 34858 日期1996年11月7日化合物具有结构（I）的化合物，组合物和作为药物的方法，其中B是-C（= O） - 或-CH 2 -O-，C是直接键或是二醇残基，羟基取代的羧酸残基或二羧酸残基，D是脂肪酸残基或脂肪醇残基，其中与相应的醇或酸形成酯键的酸残基或醇残基。

137. 发明授权

US5723619A Method for the synthesis of deoxypyridinoline 失效
标题翻译：合成脱氧吡啶啉的方法
公开(公告)号：US5723619A
公开(公告)日：1998-03-03
申请号：US782214
申请日：1997-01-13
申请人： Robert P. Hatch
发明人： Robert P. Hatch
IPC分类号： C07D213/65 , B01J27/10 , C07B61/00 , C07D213/66 , C07D213/127 , C07D213/16 , C07D213/20
CPC分类号： C07D213/66
摘要： Disclosed is a method for the chemical synthesis of deoxypyridinoline (DPD). The synthesis involves the preparation of a protected 3-hydroxypyridinium starting with a N.alpha.-protected lysine and a 5,6-epoxy-2-N-protected-O-protected-(2S)-2-aminohexanoate with subsequent deprotection to provide the desired DPD.
摘要翻译：公开了化学合成脱氧吡啶啉（DPD）的方法。合成涉及由Nα保护的赖氨酸和5,6-环氧-2-N保护的O-保护的（2S）-2-氨基己酸酯开始制备受保护的3-羟基吡啶鎓，随后进行脱保护，得到所需的DPD。

138. 发明授权

US5130437A N,N'-bis-(pyridoxal)ethylenediamine-N,N'-diacetic acid derivatives 失效
标题翻译： N，N'-二 - （吡哆醛）乙二胺-N，N'-二乙酸衍生物
公开(公告)号：US5130437A
公开(公告)日：1992-07-14
申请号：US578265
申请日：1990-09-06
申请人： Scott M. Rocklage , Steven C. Quay
发明人： Scott M. Rocklage , Steven C. Quay
IPC分类号： A61K49/06 , C07D213/66 , C07F13/00
CPC分类号： C07D213/66 , A61K49/06 , C07F13/005
摘要： Manganese(II) chelates of N,N'-bis-(pyridoxal)alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal)-1,2-cycloalkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal)-1,2-arylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal)alkylenediamine-N-acetic acids, N,N'-bis-(pyridoxal)-1,2-cycloalkylenediamine-N-acetic acids, N,N'-(pyridoxal)-1,2-arylenediamine-N-acetic acids, and their salts are highly stable, superior NMRI contrast agents. They maintain the manganese(II) ion in the +2 valence state. Preferred contrast agents are manganese(II) ion chelates of N,N'-bis-(pyridoxal)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal)trans-1,2-cyclohexylenediamine-N,N'-diacetic acid, and the salts and esters thereof.Novel chelate forming compounds are the N,N'-bis-(pyridoxal)-1,2-cycloalkylenediamine-N,N'-diacetic acids and N,N'-bis-(pyridoxal)-1,2-arylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal)alkylenediamine-N-acetic acids, N,N'-bis(pyridoxal)-1,2-cycloalkylenediamine-N-acetic acids, N,N'-bis-(pyridoxal)-1,2-arylenediamine-N-acetic acids, and their salts and esters.
摘要翻译： N，N'-双（吡哆醛）亚烷基二胺-N，N'-二乙酸，N，N'-二 - （吡哆醛）-1,2-环亚烷基二胺-N，N'-二乙酸的锰（II）螯合物，N，N'-二 - （吡哆醛）-1,2-芳基二胺-N，N'-二乙酸，N，N'-双 - （吡哆醛）亚烷基二胺-N-乙酸，N，N'-双 - （吡哆醛）-1,2-环烷二胺-N-乙酸，N，N' - （吡哆醛）-1,2-芳基二胺-N-乙酸及其盐是高度稳定的优异的NMRI造影剂。它们保持+2价态的锰（II）离子。优选的造影剂是N，N'-双 - （吡哆醛）乙二胺-N，N'-二乙酸，N，N'-双 - （吡哆醛）反-1,2-环己二胺-N ，N'-二乙酸及其盐和酯。新型螯合物形成化合物是N，N'-双 - （吡哆醛）-1,2-环烷二胺-N，N'-二乙酸和N，N'-双 - （吡哆醛）-1,2-芳基二胺-N， N，N'-二 - （吡哆醛）亚烷基二胺-N-乙酸，N，N'-双（吡哆醛）-1,2-环亚烷基二胺-N-乙酸，N，N'-双 - （吡哆醛）-1,2-芳基二胺-N-乙酸及其盐和酯。

139. 发明授权

US4994259A Improvement in the method of NMR imaging employing a manganese II chelates of N,N'-bis[pyridoxal-alkylene (or cycloalkylene) (or arylene)]-N,N'-diacetic acid derivatives 失效
标题翻译：使用N，N'-双[吡哆醛 - 亚烷基（或亚环烷基）（或亚芳基）] -N，N'-二乙酸衍生物的锰II螯合物的NMR成像方法的改进
公开(公告)号：US4994259A
公开(公告)日：1991-02-19
申请号：US380185
申请日：1989-07-14
申请人： Scott M. Rocklage , Steven C. Quay
发明人： Scott M. Rocklage , Steven C. Quay
IPC分类号： A61K49/06 , C07D213/66 , C07F13/00
CPC分类号： C07D213/66 , A61K49/06 , C07F13/005 , Y10T436/145555 , Y10T436/24
摘要： Manganese(II) chelates of N,N'-bis-(pyridoxal)-alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal)-1,2-cycloalkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal)-1,2-arylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal)-alkylenediamine-N-acetic acids, N,N'-bis-(pyridoxal)-1,2-cycloalkylenediamine-N-acetic acids, N,N'-bis-(pyridoxal)-1,2-arylenediamine-N-acetic acids, and their salts are highly stable, superior NMRI contrast agents. They maintain the manganese(II) ion in the +2 valence state. Preferred contrast agents are manganese(II) ion chelates of N,N'-bis-(pyridoxal)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal)trans-1,2-cyclohexylenediamine-N,N'-diacetic acid, and the salts and esters thereof.Novel chelate forming compounds are the N,N'-bis-(pyridoxal)-1,2-cycloalkylenediamine-N,N'-diacetic acids and N,N'-bis-(pyridoxal)1,2-arylene-diamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal)-alkylenediamine-N-acetic acids, N,N'-bis(pyridoxal)-1,2-cycloalkylenediamine-N-acetic acids, N,N'-bis-(pyridoxal)-1,2-arylenediamine-N-acetic acids, and their salts and esters.
摘要翻译： N，N'-双 - （吡哆醛） - 亚烷基二胺-N，N'-二乙酸，N，N'-双 - （吡哆醛）-1,2-环烷二胺-N，N'-二乙酸的锰（II）螯合物酸，N，N'-双 - （吡哆醛）-1,2-芳基二胺-N，N'-二乙酸，N，N'-双 - （吡哆醛） - 亚烷基二胺-N-乙酸，N，双（吡哆醛）-1,2-环亚烷基二胺-N-乙酸N，N'-双 - （吡哆醛）-1,2-芳基二胺-N-乙酸及其盐是高度稳定的，优良的NMRI造影剂。它们保持+2价态的锰（II）离子。优选的造影剂是N，N'-双 - （吡哆醛）乙二胺-N，N'-二乙酸，N，N'-双 - （吡哆醛）反-1,2-环己二胺-N ，N'-二乙酸及其盐和酯。新型螯合形成化合物是N，N'-双 - （吡哆醛）-1,2-环烷二胺-N，N'-二乙酸和N，N'-双（吡哆醛）1,2-亚芳基二胺-N N，N'-二 - （吡哆醛） - 亚烷基二胺-N-乙酸，N，N'-双（吡哆醛）-1,2-环烷二胺-N-乙酸，N，N' 双 - （吡哆醛）-1,2-芳基二胺-N-乙酸及其盐和酯。

140. 发明授权

US4978763A Novel manganese(II) DTPA chelate 失效
标题翻译：新型锰（II）DTPA螯合物
公开(公告)号：US4978763A
公开(公告)日：1990-12-18
申请号：US370483
申请日：1989-06-23
申请人： Scott M. Rocklage , William P. Cacheris , Gene Jamieson
发明人： Scott M. Rocklage , William P. Cacheris , Gene Jamieson
IPC分类号： A61K49/06 , C07C229/16 , C07D213/66 , C07D257/02 , C07D273/00 , C07F9/6558
CPC分类号： C07D213/66 , A61K49/06 , C07C229/16 , C07D257/02 , C07D273/00 , C07F9/65583
摘要： The process of this invention for preparing Mn(II) chelate comprises forming the Mn(II) chelate by mixing manganese(II) oxide (insoluble) with an aqueous suspension comprising a molar equivalent or molar excess of the insoluble protonated chelating compound at a temperature of from 20.degree. to 50.degree. C. When the reaction is carried out with a protonated chelating agent in the absence of base, a precipitate of the protonated Mn(II) chelate is formed. A low osmolarity Mn(II) chelate solution can be formed from the precipitates by dissolving them in an aqueous solution of base. When the initial chelate forming reaction is carried out in a solution containing a molar equivalent or excess of sodium hydroxide, a low osmolarity solution of the Mn(II) chelate is directly formed with most chelating agents. Preferred chelating compounds for this process include DPDP, DTPA, DCTA, EDTP, DOTA, DOXA, DO3A and EDTA. The Mn(II) chelate precipitates and low osmolarity solutions formed by the above processes are also aspects of this invention.
摘要翻译：本发明制备Mn（II）螯合物的方法包括通过将锰（II）氧化物（不溶性）与包含摩尔当量或摩尔过量的不溶性质子化螯合化合物的水悬浮液在温度下混合形成Mn（II）螯合物为20〜50℃。当不存在碱时，用质子化螯合剂进行反应时，形成质子化的Mn（II）螯合物的沉淀物。通过将它们溶解在碱的水溶液中，可以通过沉淀物形成低摩尔渗透浓度的Mn（II）螯合溶液。当初始螯合物形成反应在含有摩尔当量或过量氢氧化钠的溶液中进行时，Mn（II）螯合物的低渗透压溶液与大多数螯合剂直接形成。用于该方法的优选螯合化合物包括DPDP，DTPA，DCTA，EDTP，DOTA，DOXA，DO3A和EDTA。通过上述方法形成的Mn（II）螯合物沉淀物和低摩尔渗压浓度溶液也是本发明的一个方面。

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