公开(公告)号：US4565827A

公开(公告)日：1986-01-21

申请号：US315408

申请日：1981-10-27

申请人： Istvan Szekely ,  Marianna Lovasz nee Gaspar ,  Gabor Kovacs ,  Krisztina Kekesi ,  Sandor Botar ,  Karoly Horvath ,  Peter Kormoczy ,  Pal Hadhazy ,  Istvan Rakoczy ,  Laszlo Fesus

发明人： Istvan Szekely ,  Marianna Lovasz nee Gaspar ,  Gabor Kovacs ,  Krisztina Kekesi ,  Sandor Botar ,  Karoly Horvath ,  Peter Kormoczy ,  Pal Hadhazy ,  Istvan Rakoczy ,  Laszlo Fesus

IPC分类号： C07C405/00 ,  C07D307/937 ,  C07D307/935 ,  A61K31/34 ,  A61K31/557

CPC分类号： C07D307/937 ,  C07C405/00

摘要： The invention relates to new, 7-substituted PGI.sub.2 -derivatives of formula (I) ##STR1## The new compounds have valuable therapeutical properties, and in particular show prostacyclin-like effects.

摘要翻译： 本发明涉及式（I）的新的7-取代的PGI 2衍生物。（I）新化合物具有有价值的治疗特性，特别是显示前列环素样效应。

公开(公告)号：US4451483A

公开(公告)日：1984-05-29

申请号：US367068

申请日：1982-04-09

申请人： Istvan Szekely ,  Krisztina Kekesi ,  Mariann Lovasz nee Gaspar ,  Sandor Botar ,  Pal Hadhazy ,  Istvan Rakoczi ,  Laszlo Muszbek ,  Judit Skopal ,  Istvan Stadler ,  Karoly Horvath ,  Gabor Kovacs ,  Peter Kormoczy

发明人： Istvan Szekely ,  Krisztina Kekesi ,  Mariann Lovasz nee Gaspar ,  Sandor Botar ,  Pal Hadhazy ,  Istvan Rakoczi ,  Laszlo Muszbek ,  Judit Skopal ,  Istvan Stadler ,  Karoly Horvath ,  Gabor Kovacs ,  Peter Kormoczy

IPC分类号： A61K31/5575 ,  C07C405/00 ,  C07D307/937 ,  A61K31/34 ,  C07D307/935

CPC分类号： C07D307/937 ,  C07C405/00 ,  C07C405/0041 ,  Y10S514/822

摘要： 2,3,4-trinor-1,5-inter-m-phenylene-prostacycline derivatives of the formula (I), ##STR1## wherein R.sup.1 is hydrogen, a C.sub.1-4 alkyl group, an alkali metal cation or a primary, secondary, tertiary or quaternary ammonium cation,R.sup.2 and R.sup.3 each represent hydrogen or a C.sub.1-4 alkanoyl, benzoyl, substituted benzoyl, tetrahydropyranyl, ethoxyethyl or tri-(C.sub.1-4 alkyl)-silyl group,R.sup.4 is hydrogen or a C.sub.1-4 alkyl group, andR.sup.5 is a hexyl, heptyl, phenoxymethyl or m-trifluoromethylphenoxymethyl group, orR.sup.5 represents a group of the general formula ##STR2## and in this latter formula Z is an amino group or an optionally halo-substituted C.sub.1-4 alkanoylamino, benzoylamino or tosylamino group, andR.sup.6 is a C.sub.4-6 alkyl, phenyl or benzyl group,are prepared by reacting a bicyclic lactol of the formula (II), ##STR3## with a reactive phosphorane prepared from a triphenyl-m-carbobenzylphosphonium halide and a strong base, optionally esterifying the resulting prostaglandin derivative and, whenever it contains a free amino group, protecting this amino group by acylation, reacting then the prostaglandin derivative with an electrophilic reagent of the formula E-X, wherein X is halogen atom and E is halogen atom or an acetyl, trifluoroacetyl or N-succinimido group, and subjecting the resulting halogenated PGI.sub.1 derivative to hydrogen halide elimination. The compounds of the formula (I) possess valuable biological effects and can be applied in therapy primarily as blood platelet aggregation inhibiting agents.

摘要翻译： 式（I）的2,3,4-三硝基-1,5-间 - 间 - 亚苯基 - 前列环素衍生物，其中R 1是氢，C 1-4烷基，碱金属阳离子或 伯，仲，叔或季铵阳离子，R2和R3各自表示氢或C1-4烷酰基，苯甲酰基，取代的苯甲酰基，四氢吡喃基，乙氧基乙基或三（C1-4烷基） - 甲硅烷基，R4是氢或 C 1-4烷基，R 5为己基，庚基，苯氧基甲基或间三氟甲基苯氧基甲基，或R 5表示通式“IMAGE”的基团，在后一式中Z为氨基或任意卤素取代的C1 -4烷酰基氨基，苯甲酰氨基或甲苯磺酰氨基，R6是C4-6烷基，苯基或苄基，是通过使式（II）的双环内酰醇与式（II）的双环内酰醇与由 三苯基-m-苄基苄基卤化鏻和强碱，任选地酯化所得的前列腺素衍生物，并且每当其含有时 游离氨基，通过酰化保护该氨基，然后将前列腺素衍生物与式EX的亲电试剂反应，其中X是卤素原子，E是卤素原子或乙酰基，三氟乙酰基或N-琥珀酰亚胺基，并使 得到的卤化PGI1衍生物消除卤化氢。 式（I）化合物具有有价值的生物学效应，可用作主要作为血小板聚集抑制剂的治疗。

公开(公告)号：US4438132A

公开(公告)日：1984-03-20

申请号：US368013

申请日：1982-04-13

申请人： Gaza Galambos ,  Vilmos Simonidesz ,  Istvan Szekely ,  Jozsef Ivanics ,  Krisztina Kekesi ,  Gabor Kovacs ,  Istvan Stadler ,  Peter Kormoczy ,  Karoly Horvath

发明人： Gaza Galambos ,  Vilmos Simonidesz ,  Istvan Szekely ,  Jozsef Ivanics ,  Krisztina Kekesi ,  Gabor Kovacs ,  Istvan Stadler ,  Peter Kormoczy ,  Karoly Horvath

IPC分类号： C07D307/935 ,  A61K31/557 ,  A61P1/04 ,  A61P7/02 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  A61P11/08 ,  C07C405/00 ,  C07D307/937

CPC分类号： C07D307/937 ,  C07C317/00 ,  Y02P20/55 ,  Y10S514/824 ,  Y10S514/926 ,  Y10S514/927

摘要： The invention relates to a process for the preparation of novel 4-oxo-PGI.sub.2 derivatives of formula I ##STR1## where (a) compounds of formula III ##STR2## are oxidized, then the obtained 5-substituted-4-oxo-PGI.sub.1 derivatives of general formula II ##STR3## are eliminated by the splitting off of the W-H-molecule, or (b) the compounds of formula IV ##STR4## are reacted in a solvent in the presence of a catalyst with compounds of general formula V ##STR5## then the obtained compounds of formula I are transformed if desired by saponification, hydrolysis, salt formation, insertion of a protection group to another compound which belongs to the compounds of formula I, too.The pharmaceutical products of the invention can be used for the treatment of circulatory diseases, they inhibit the aggregation of blood plaques, dilate the bronchi and inhibit the secretion of gastric acid.

摘要翻译： 本发明涉及一种制备式I（I）的新型4-氧代-GII 2衍生物的方法，其中（a）式III的化合物（XIIIX）被氧化，然后得到5-取代的 通过分解WH分子来消除通式II（XIIX）的4-氧代-PGI1衍生物，或（b）式IV化合物（XIVX）在溶剂中在 然后如果需要，通过皂化，水解，形成盐，将保护基团插入另一种属于式（I）化合物的化合物的化合物，转化所得到的式I化合物， 我也。 本发明的药物可用于治疗循环系统疾病，抑制血斑聚集，扩张支气管，抑制胃酸分泌。

公开(公告)号：US06498143B1

公开(公告)日：2002-12-24

申请号：US09449512

申请日：1999-11-24

申请人： Victoria Beck ,  Karoly Horvath

发明人： Victoria Beck ,  Karoly Horvath

IPC分类号： C07K1400

CPC分类号： G01N33/6893 ,  A61K31/045 ,  A61K31/047 ,  A61K31/12 ,  A61K31/121 ,  A61K31/201 ,  A61K31/495 ,  A61K31/575 ,  A61K36/48 ,  A61K36/484 ,  A61K38/2235 ,  G01N2333/645 ,  G01N2800/28 ,  G01N2800/38 ,  A61K2300/00

摘要： A novel relationship between pancreatico-biliary secretion and autistic syndrome is disclosed. This relationship enables a novel therapy for the treatment of the symptoms of autistic syndromes, comprising the administration of a therapeutically effective, preferably intravenous, dose of secretin to an individual with autistic syndrome. The relationship further enables a differential diagnosis for autistic syndrome, comprising an analysis of an individual's blood and/or intestinal tissue for the presence of secretin and comparison of the level of secretin to known norms.

摘要翻译： 公开了胰胆汁分泌与自闭症综合征之间的新颖关系。 这种关系使得能够进行治疗自闭症综合征的症状的新疗法，其包括向具有自闭症综合征的个体施用治疗有效的，优选静脉内的剂量的促胰液素。 该关系进一步使自闭症综合征的鉴别诊断，包括对个体血液和/或肠组织的分析以了解胰液素的存在以及分泌素水平与已知规范的比较。

公开(公告)号：US4473697A

公开(公告)日：1984-09-25

申请号：US458266

申请日：1983-01-17

申请人： Csaba Gonczi ,  Dezso Korbonits ,  Endre Palosi ,  Pal Kiss ,  Gergely Heja ,  Judit Kun ,  Maria Szomor nee Wundele ,  Ida Szvoboda nee Kanzel ,  Ede Marvanyos ,  Karoly Horvath ,  Vera Kovacs nee Mindler ,  Livia Nagy nee Koranyi

发明人： Csaba Gonczi ,  Dezso Korbonits ,  Endre Palosi ,  Pal Kiss ,  Gergely Heja ,  Judit Kun ,  Maria Szomor nee Wundele ,  Ida Szvoboda nee Kanzel ,  Ede Marvanyos ,  Karoly Horvath ,  Vera Kovacs nee Mindler ,  Livia Nagy nee Koranyi

IPC分类号： C07D235/30 ,  C07D235/32

CPC分类号： C07D235/32 ,  C07D235/30

摘要： A new process is disclosed for the preparation of a compound of the formula (VIII) ##STR1## wherein R.sup.1 is hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-3 alkoxy, or trifluoromethyl;R.sup.5 is amino or C.sub.1-4 alkoxycarbonylamino; or a salt thereof, which comprises reacting a compound of the formula (II) ##STR2## with gaseous chlorine and a rhodanide of the formula (III)R--SCN (III)wherein R represents a metal ion or ammonium.

摘要翻译： 公开了用于制备式（VIII）化合物（VIII）的新方法，其中R 1是氢，卤素，C 1-4烷基，C 1-3烷氧基或三氟甲基; R5是氨基或C1-4烷氧基羰基氨基; 其包括使式（II）化合物（II）与气态氯和式（III）的R-SCN（III）的硫氰酸盐反应，其中R表示金属离子或铵。

公开(公告)号：US07091182B2

公开(公告)日：2006-08-15

申请号：US10327591

申请日：2002-12-20

申请人： Victoria Beck ,  Karoly Horvath

发明人： Victoria Beck ,  Karoly Horvath

IPC分类号： C07K14/00

CPC分类号： G01N33/6893 ,  A61K31/045 ,  A61K31/047 ,  A61K31/12 ,  A61K31/121 ,  A61K31/201 ,  A61K31/495 ,  A61K31/575 ,  A61K36/48 ,  A61K36/484 ,  A61K38/2235 ,  G01N2333/645 ,  G01N2800/28 ,  G01N2800/38 ,  A61K2300/00

摘要： A novel relationship between pancreatico-biliary secretion and autistic syndrome is disclosed. This relationship enables a novel therapy for the treatment of the symptoms of autistic syndromes, comprising the administration of a therapeutically effective, preferably intravenous, dose of secretin to an individual with autistic syndrome. The relationship further enables a differential diagnosis for autistic syndrome, comprising an analysis of an individual's blood and/or intestinal tissue for the presence of secretin and comparison of the level of secretin to known norms.

公开(公告)号：US5981590A

公开(公告)日：1999-11-09

申请号：US819624

申请日：1997-03-17

申请人： Pinaki Panigrahi ,  Karoly Horvath ,  Ira H. Gewolb

发明人： Pinaki Panigrahi ,  Karoly Horvath ,  Ira H. Gewolb

IPC分类号： A61K31/198 ,  A61K31/195

CPC分类号： A61K31/198

摘要： A method of preventing necrotizing tissue injury in the gastrointestinal tract comprising orally administering glutamine is disclosed. Glutamine protects tissues along the gastrointestinal tract by blocking translocation of bacterial agents such as gram (-) bacteria, other infectious agents, toxins, chemicals and injurious substances. The intraluminal/apical presence of the glutamine optimizes mucosal defense and increases nutrient absorption. Enteral glutamine is useful in treating neonatal necrotizing enterocolitis for reducing inflammation caused by bacterial translocation and injury. Oral glutamine is also useful in treating gastrointestinal dysfunctions. When glutamine is orally administered, it coats gastrointestinal mucosa thereby treating infectious and/or inflammatory conditions of the gastrointestinal tract. It is useful in treating pathologic conditions with lowered transepithelial electrical resistance (TEER) by acting as a curative agent.

摘要翻译： 公开了一种预防胃肠道坏死组织损伤的方法，其包括口服施用谷氨酰胺。 谷氨酰胺通过阻止细菌剂如克（ - ）细菌，其他感染因子，毒素，化学物质和有害物质的移位来保护沿着胃肠道的组织。 谷氨酰胺的管腔内/顶端存在优化粘膜防御并增加营养吸收。 肠内谷氨酰胺可用于治疗新生儿坏死性小肠结肠炎，以减少由细菌易位和损伤引起的炎症。 口服谷氨酰胺也可用于治疗胃肠功能障碍。 当口服施用谷氨酰胺时，其涂覆胃肠粘膜，从而治疗胃肠道的感染性和/或炎性病症。 通过作为治疗剂治疗具有降低的跨上皮电阻（TEER）的病理状况是有用的。

公开(公告)号：US6020310A

公开(公告)日：2000-02-01

申请号：US80631

申请日：1998-05-19

申请人： Victoria Beck ,  Karoly Horvath

发明人： Victoria Beck ,  Karoly Horvath

IPC分类号： A61K31/045 ,  A61K31/047 ,  A61K31/12 ,  A61K31/121 ,  A61K31/201 ,  A61K31/495 ,  A61K31/575 ,  A61K36/48 ,  A61K38/22 ,  A61K38/54 ,  A61K45/00 ,  A61P25/00 ,  G01N33/68 ,  G01N33/74 ,  A61K38/00

CPC分类号： G01N33/6893 ,  A61K31/045 ,  A61K31/047 ,  A61K31/12 ,  A61K31/121 ,  A61K31/201 ,  A61K31/495 ,  A61K31/575 ,  A61K36/48 ,  A61K36/484 ,  A61K38/2235 ,  G01N2333/645 ,  G01N2800/28 ,  G01N2800/38

摘要： A novel relationship between pancreatico-biliary secretion and autistic syndrome is disclosed. This relationship enables a novel therapy for the treatment of the symptoms of autistic syndromes, comprising the administration of a therapeutically effective, preferably intravenous, dose of secretin to an individual with autistic syndrome. The relationship further enables a differential diagnosis for autistic syndrome, comprising an analysis of an individual's blood and/or intestinal tissue for the presence of secretin and comparison of the level of secretin to known norms.

公开(公告)号：US4599428A

公开(公告)日：1986-07-08

申请号：US591767

申请日：1984-03-21

申请人： Csaba Gonczi ,  Dezso Korbonits ,  Endre Palosi ,  Pal Kiss ,  Gergely Heja ,  Judit Kun ,  Maria Szomor nee Wundele ,  Ida Szvoboda nee Kanzel ,  Ede Marvanyos ,  Karoly Horvath ,  Vera Kovacs nee Mindler ,  Livia Nagy nee Koranyi

发明人： Csaba Gonczi ,  Dezso Korbonits ,  Endre Palosi ,  Pal Kiss ,  Gergely Heja ,  Judit Kun ,  Maria Szomor nee Wundele ,  Ida Szvoboda nee Kanzel ,  Ede Marvanyos ,  Karoly Horvath ,  Vera Kovacs nee Mindler ,  Livia Nagy nee Koranyi

IPC分类号： C07D235/30 ,  C07D235/32

CPC分类号： C07D235/30 ,  C07D235/32

摘要： A process is disclosed for the preparation of a compound of the formula (XI) ##STR1## or a salt thereof, wherein R.sup.1 is hydrogen, halogen, C.sub.1 to C.sub.4 alkyl, C.sub.1 to C.sub.3 alkoxy, or trifluoromethyl;R.sup.5 is amino or C.sub.1 to C.sub.4 alkoxycarbonylamino; andR.sup.4" is C.sub.1 to C.sub.6 alkyl, C.sub.2 to C.sub.6 alkenyl, C.sub.2 to C.sub.6 alkynyl, cyclohexyl, benzyl, or 2-phenyl-ethyl, which comprises the steps of:(a) reacting a compound of the formula (VIII) ##STR2## or a salt thereof, with a basic nucleophilic compound to yield a salt of the formula (IX) ##STR3## wherein R.sup.4' is a lone pair of electrons, in which case an alkali metal or alkali earth metal cation forms a salt with the sulfur atom; and(b) reacting a salt of the formula (IX) with a compound of the formula (X)R.sup.4' --QwhereinQ is hydroxyl, halogen, 1/2SO.sub.4, 1/3PO.sub.3, SO.sub.3 C.sub.6 H.sub.5, or SO.sub.3 C.sub.6 H.sub.4 CH.sub.3 to yield the desired product.

摘要翻译： 公开了制备式（XI）化合物或其盐的方法，其中R 1是氢，卤素，C 1至C 4烷基，C 1至C 3烷氧基或三氟甲基; R5是氨基或C1-C4烷氧基羰基氨基; 并且R 4“为C 1至C 6烷基，C 2至C 6烯基，C 2至C 6炔基，环己基，苄基或2-苯基 - 乙基，其包括以下步骤：（a）使式（Ⅷ） IMAGE>或其盐与碱性亲核性化合物反应得到式（Ⅸ）的盐，其中R4'是一对电子，在这种情况下，碱金属或碱土金属阳离子与 硫原子; 和（b）使式（IX）的盐与式（X）R4'-Q的化合物反应，其中Q是羟基，卤素，1 / 2SO 4，1 / 3PO 3，SO 3 C 6 H 5或SO 3 C 6 H 4 CH 3，得到所需产物 。