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1. 发明授权

US4590209A Alkoxy-acyl carnitines and pharmaceutical compositions containing same 失效
标题翻译：烷氧基酰基肉碱和含有它们的药物组合物
公开(公告)号：US4590209A
公开(公告)日：1986-05-20
申请号：US522546
申请日：1983-08-11
申请人： Claudio Cavazza , Paolo De Witt , Maria O. Tinti , Emma Quaresima
发明人： Claudio Cavazza , Paolo De Witt , Maria O. Tinti , Emma Quaresima
IPC分类号： C07C227/16 , A61K20060101 , A61K31/14 , A61K31/195 , A61K31/205 , A61K31/22 , A61K31/24 , A61K31/265 , A61P9/00 , A61P9/06 , A61P25/02 , C07C20060101 , C07C67/00 , C07C227/00 , C07C229/22 , C07C101/30
CPC分类号： C07C227/16 , C07C229/22
摘要： A novel class of alkoxy-acyl carnitines, wherein the alkoxy-acyl radical has from 4 to 6 carbon atoms (tipically: methoxypropionyl, ethoxypropionyl and propoxyacetyl) is prepared by reacting a solution of a carnitine salt in an organic solvent with an alkoxy-acyl halogenide, thus obtaining the corresponding salt of alkoxy-acyl carnitine. By eluting an aqueous solution of this salt through a column of an ion exchange resin activated in Cl.sup.- or Br.sup.- form, the chloride or bromide of alkoxy-acyl carnitine is obtained. The alkoxy-acyl carnitines are therapeutically effective in the treatment of cardiac disorders, hyperlipidaemias and hyperlipoproteinaemias.
摘要翻译：一种新型的烷氧基酰基肉碱，其中烷氧基 - 酰基具有4-6个碳原子（特别是甲氧基丙酰基，乙氧基丙酰基和丙氧基乙酰基）是通过使肉碱盐在有机溶剂中的溶液与烷氧基酰基卤化物，从而得到相应的烷氧基酰基肉碱盐。通过用Cl-或Br-型活化的离子交换树脂柱洗脱该盐水溶液，得到烷氧基酰基肉碱的氯化物或溴化物。烷氧基酰基肉碱在治疗心脏病，高脂血症和高脂蛋白血症方面是治疗上有效的。

2. 发明授权

US4766222A Novel class of acyl-derivatives of carnitine process for preparing same and therapeutic use thereof 失效
标题翻译：肉碱制备方法的新一类酰基衍生物及其治疗用途
公开(公告)号：US4766222A
公开(公告)日：1988-08-23
申请号：US68748
申请日：1987-06-30
申请人： Claudio Cavazza , Paolo De Witt , Maria O. Tinti
发明人： Claudio Cavazza , Paolo De Witt , Maria O. Tinti
IPC分类号： A61K31/215 , A61K20060101 , A61K31/14 , A61K31/195 , A61K31/205 , A61K31/38 , A61P3/06 , A61P7/00 , A61P9/00 , C07C20060101 , C07C67/00 , C07C227/00 , C07C227/16 , C07C229/22 , C07D333/22 , C07D333/24 , C07D333/32 , C07D333/38 , C07D339/02 , C07D339/04 , C07C101/12
CPC分类号： C07C229/22 , A61K9/0019 , A61K9/0095 , A61K9/12 , A61K9/2054 , A61K9/2059 , C07C2101/08 , C07C2101/14 , C07C2101/16
摘要： A novel class of acyl-derivatives of carnitine is disclosed wherein the acyl radical is either the radical of unsaturated organic acids (typically, acrylic acid) or the radical of saturated organic acids substituted with tert-alkyl, cycloalkyl, cycloalkenyl, alkoxyl, heterocyclic and carboalkoxylradicals, or with aldehyde or hydroxy groups. These acyl-derivatives of carnitine are useful therapeutical agents in the treatment of cardiac disorders, hyperlipidaemias and hyperlipoproteinaemias.
摘要翻译：公开了一类新的肉碱酰基衍生物，其中酰基是不饱和有机酸（通常为丙烯酸）或被叔烷基，环烷基，环烯基，烷氧基，杂环取代的饱和有机酸基团或与醛或羟基相结合。肉碱的这些酰基衍生物是治疗心脏病，高脂血症和高脂蛋白血症的有用治疗剂。

3. 发明授权

US4859698A Novel class of acyl-derivatives of carnitine, process for preparing same and therapeutic use thereof 失效
标题翻译：新一类肉碱的酰基衍生物，其制备方法及其治疗用途
公开(公告)号：US4859698A
公开(公告)日：1989-08-22
申请号：US200641
申请日：1988-05-31
申请人： Claudio Cavazza , Paolo De Witt , Maria O. Tinti
发明人： Claudio Cavazza , Paolo De Witt , Maria O. Tinti
IPC分类号： A61K31/215 , A61K20060101 , A61K31/14 , A61K31/195 , A61K31/205 , A61K31/38 , A61P3/06 , A61P7/00 , A61P9/00 , C07C20060101 , C07C67/00 , C07C227/00 , C07C227/16 , C07C229/22 , C07D333/22 , C07D333/24 , C07D333/32 , C07D333/38 , C07D339/02 , C07D339/04
CPC分类号： C07C229/22 , A61K9/0019 , A61K9/0095 , A61K9/12 , A61K9/2054 , A61K9/2059 , C07C2101/08 , C07C2101/14 , C07C2101/16
摘要： A novel class of acyl-derivatives of carnitine is disclosed wherein the acyl radical is either the radical of unsaturated organic acids (typically, acrylic acid) or the radical of saturated organic acids substituted with tert-alkyl, cycloalkyl, cycloalkenyl, alkoxyl, heterocyclic and carboalkoxylradicals, or with aldehyde or hydroxy groups. These acyl-derivatives of carnitine are useful therapeutical agents in the treatment of cardiac disorders, hyperlipidaemias and hyperlipoproteinaemias.
摘要翻译：公开了一类新的肉碱酰基衍生物，其中酰基是不饱和有机酸（通常为丙烯酸）或被叔烷基，环烷基，环烯基，烷氧基，杂环取代的饱和有机酸基团或与醛或羟基相结合。肉碱的这些酰基衍生物是治疗心脏病，高脂血症和高脂蛋白血症的有用治疗剂。

4. 发明授权

US4343947A Carnitinamides of optically active aminoacids 失效
标题翻译：光学活性氨基酸的肉碱酰胺
公开(公告)号：US4343947A
公开(公告)日：1982-08-10
申请号：US220492
申请日：1980-12-29
申请人： Paolo De Witt , Maria O. Tinti
发明人： Paolo De Witt , Maria O. Tinti
IPC分类号： A61K20060101 , A61K31/16 , A61K31/205 , C07C20060101 , C07C237/12 , C07C323/25 , C07D233/58 , C07D233/64 , C07C101/26 , C07C101/30 , C07C101/32
CPC分类号： C07C237/12 , C07C323/58
摘要： Amides of carnitine or acyl-carnitines having general formula: ##STR1## wherein X.sup.- is a halogen anion, e.g. the chloride anionR is either hydrogen or an acyl radical, such as acetyl, propionyl or butyryl; andY is the residue of an optically active esterified amino-acid (e.g. the residue of L-phenylglycine methyl ester, ##STR2## are prepared by either (a) directly condensing D,L-carnitine (or acyl-D,L-carnitine) with an ester of an optically active aminoacid, or (b) preparing the acid halogenide of D,L-carnitine or acyl-D,L-carnitine and subsequently condensing it with an ester of an optically active aminoacid.The mixture of the diastereoisomer amides thus obtained is resolved by fractional crystallization from organic solvents into the respective separated diastereoisomers.These optically active amides are useful therapeutic agents for treating cardiac disorders, hyperlipidaemias and hyperlipoproteinaemias and, furthermore, can be hydrolyzed with procedures known per se into L-carnitine and D-carnitine, respectively.
摘要翻译：具有以下通式的肉碱或酰基肉碱的酰胺：其中X是卤素阴离子，例如，氯离子R是氢或酰基，如乙酰基，丙酰基或丁酰基; 并且Y是光学活性酯化氨基酸的残基（例如，L-苯基甘氨酸甲酯的残基，通过以下方法制备：（a）直接冷凝D，L-肉毒碱（或酰基-D，L-肉毒碱），或（b）制备D，L-肉碱或酰基-D，L-肉毒碱的酰卤，然后将其与光学活性氨基酸的酯缩合，非对映异构体的混合物这些光学活性酰胺是治疗心脏疾病，高脂血症和高脂蛋白血症的有用治疗剂，此外，可以用本身已知的方法将其水解成L-肉碱和 D-肉碱分别。

5. 发明授权

US5491260A Process for manufacturing L-(-)-carnitine from derivatives having a configuration opposite to that of L-(-)-carnitine 失效
标题翻译：具有与L - （ - ） - 肉碱相反的结构的衍生物制造L - （ - ） - 肉碱的方法
公开(公告)号：US5491260A
公开(公告)日：1996-02-13
申请号：US224522
申请日：1994-04-07
申请人： Fabio Giannessi , Roberto Castagnani , Maria O. Tinti , Francesco De Angelis , Paolo De Witt , Domenico Misiti
发明人： Fabio Giannessi , Roberto Castagnani , Maria O. Tinti , Francesco De Angelis , Paolo De Witt , Domenico Misiti
IPC分类号： C12P13/00 , C07B57/00 , C07C227/30 , C07C227/32 , C07C229/22 , C07D305/12 , C12P41/00 , C07C227/18 , C07C253/34
CPC分类号： C07C227/32 , C07C229/22 , C07D305/12
摘要： A Process for Preparing L-(-)-carnitine is disclosed which comprises acylating D-(+)-carnitinenitrile or D-(+)-carnitineamide to their respective acyl derivatives which, via acid hydrolysis, yield D-(+)-carnitine which is converted to the lactone of L-(-)-carnitine. The lactone when in base yields L-(-)-carnitine.
摘要翻译：公开了制备L-（ - ） - 肉碱的方法，该方法包括将D-（+） - 肉毒碱或D - （+） - 肉碱酰胺酰化成各自的酰基衍生物，其通过酸水解产生D - （+） - 肉碱其被转化为L - （ - ） - 肉碱的内酯。内酯在碱中产生L - （ - ） - 肉碱。

6. 发明授权

US06593478B2 Stereospecific hydrolysis of optically active esters 失效
标题翻译：光学活性酯的立体特异性水解
公开(公告)号：US06593478B2
公开(公告)日：2003-07-15
申请号：US10168792
申请日：2002-06-24
申请人： Oreste Piccolo , Roberto Castagnani , Paolo De Witt
发明人： Oreste Piccolo , Roberto Castagnani , Paolo De Witt
IPC分类号： C07D30706
CPC分类号： C07D307/33 , C07C227/32 , C07D307/20 , C07C229/22
摘要： A new, more efficient and highly stereospecific process is described for the preparation of compounds with general formula (R)-(I) and of absolute configuration (R), where the groups M, W, Q and Q1 are as defined in the description, starting from compounds of absolute configuration (S) by hydrolysis, in the presence of acids, of the corresponding esterified derivatives. The (R)-(I) products obtained with the process described herein are chiral synthons useful for the production of enanthiomerically pure drugs. The preparation of (R)-carnitine is also provided.
摘要翻译：描述了制备具有通式（R） - （I）和绝对构型（R）的化合物的新的，更有效和高度立体定向的方法，其中基团M，W，Q和Q 1如说明书中所定义从具有相应酯化衍生物的酸存在下通过水解的绝对构型（S）化合物开始。通过本文所述的方法获得的（R） - （I）产物是可用于生产精神药物的手性合成物。还提供了（R） - 肉碱的制备。

7. 发明授权

US06548693B2 Nitriloxy derivatives of (R) and (S)-carnitine 失效
公开(公告)号：US06548693B2
公开(公告)日：2003-04-15
申请号：US10119954
申请日：2002-04-11
申请人： Oreste Piccolo , Roberto Castagnani , Paolo De Witt
发明人： Oreste Piccolo , Roberto Castagnani , Paolo De Witt
IPC分类号： C07C20300
CPC分类号： C07C227/16 , C07B2200/07 , C07C227/18 , C07C227/32 , C07C229/22
摘要： Carnitine derivatives of formula (I) are described in racemic and/or optically active form, as well as the process for their preparation and their use as pharmaceutical anti-angina active ingredients for the treatment of ischaemic heart disease. Also described is a process for producing the (R)-carnitine enantiomer from (S)-carnitine (or vice versa), using the derivatives of formula (I).

8. 再颁专利

USRE32398E Electrolytic process and electrolytic cell for the preparation of organic compounds 失效
标题翻译：电解过程和电解槽用于制备有机化合物
公开(公告)号：USRE32398E
公开(公告)日：1987-04-14
申请号：US789819
申请日：1985-10-21
申请人： Paolo De Witt , Enrico Benedetto
发明人： Paolo De Witt , Enrico Benedetto
IPC分类号： C25B9/00 , B01D57/00 , B01D57/02 , B01D61/44 , C25B1/14 , C25B1/22 , C25B3/00 , C25B7/00 , C25B9/08 , C25B13/00 , C25B13/08
CPC分类号： C25B3/00 , C07C255/00
摘要： There is described an electrolytic cell and a process for removing the halide or other anion from an organic salt having as general formula A+X--, wherein A+ is an organic cation and X-- is a halide or other anion. Typical compounds of this type are the hydrohalides of nitrogen bases or other salts or hydrosalts of such bases or compounds notably salts (hydrohalides) of quaternary ammonium bases or of amines or amides. However the process herein contemplated may be applied to the removal of anions, e.g. chloride, which are present as an impurity or in combination with the organic compound.

9. 发明授权

US06395923B2 Nitriloxy derivatives of (R) and (S)-carnitine 失效
标题翻译：（R）和（S） - 肉碱的硝基氧基衍生物
公开(公告)号：US06395923B2
公开(公告)日：2002-05-28
申请号：US09804270
申请日：2001-03-13
申请人： Oreste Piccolo , Roberto Castagnani , Paolo De Witt
发明人： Oreste Piccolo , Roberto Castagnani , Paolo De Witt
IPC分类号： C07C22900
CPC分类号： C07C227/16 , C07B2200/07 , C07C227/18 , C07C227/32 , C07C229/22
摘要： Carnitine derivatives of formula (I) are described in racemic and/or optically active form, as well as the process for their preparation and their use as pharmaceutical anti-angina active ingredients for the treatment of ischaemic heart disease. Also described is a process for producing the (R)-carnitine enantiomer from (S)-carnitine (or vice versa), using the derivatives of formula (I).
摘要翻译：式（I）的肉碱衍生物以外消旋和/或旋光形式描述，以及其制备方法及其作为用于治疗缺血性心脏病的药物抗心绞痛活性成分的用途。还描述了一种用于使用式（I）的衍生物从（S） - 肉碱（或反之亦然）产生（R） - 肉碱对映异构体。

10. 发明授权

US4521285A Electrolytic process for the preparation of organic compounds 失效
标题翻译：用于制备有机化合物的电解过程
公开(公告)号：US4521285A
公开(公告)日：1985-06-04
申请号：US551817
申请日：1983-11-15
申请人： Paolo De Witt , Enrico Benedetto
发明人： Paolo De Witt , Enrico Benedetto
IPC分类号： C25B9/00 , B01D57/00 , B01D57/02 , B01D61/44 , C25B1/14 , C25B1/22 , C25B3/00 , C25B7/00 , C25B9/08 , C25B13/00 , C25B13/08
CPC分类号： C25B3/00 , C07C255/00
摘要： There is described an electrolytic cell and a process for removing the halide or other anion from an organic salt having as general formula A.sup.+ X.sup.-, wherein A.sup.+ is an organic cation and X.sup.- is a halide or other anion. Typical compounds of this type are the hydrohalides of nitrogen bases or other salts or hydrosalts of such bases or compounds notably salts (hydrohalides) of quaternary ammonium bases or of amines or amides. However the process herein contemplated may be applied to the removal of anions, e.g. chloride, which are present as an impurity or in combination with the organic compound.
摘要翻译：描述了一种电解槽和从具有通式A + X-的有机盐除去卤化物或其它阴离子的方法，其中A +是有机阳离子，X是卤化物或其它阴离子。这种类型的典型化合物是这些碱或氮化物的其它盐或氢盐，特别是季铵碱或胺或酰胺的盐（氢卤化物）。然而，本文预期的方法可以应用于除去阴离子，例如阴离子。氯化物，其以杂质存在或与有机化合物组合存在。

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