公开(公告)号：US4748175A

公开(公告)日：1988-05-31

申请号：US947700

申请日：1986-12-30

申请人： Endre Kasztreiner ,  Gyorgy Rabloczky ,  Nandor Makk ,  Gyorgy Cseh ,  Maria Kuhar nee Kurthy ,  Eszter Diesler ,  Laszlo Jaszlits ,  Laszlo Sebestyen ,  Janos Wellmann ,  Aniko Tegdes ,  Judit Sarossy nee Kincsesy ,  Peter Matyus ,  Andras Varro ,  Laszlo Szam ,  Sarolta Vegvari nee Gyurki

发明人： Endre Kasztreiner ,  Gyorgy Rabloczky ,  Nandor Makk ,  Gyorgy Cseh ,  Maria Kuhar nee Kurthy ,  Eszter Diesler ,  Laszlo Jaszlits ,  Laszlo Sebestyen ,  Janos Wellmann ,  Aniko Tegdes ,  Judit Sarossy nee Kincsesy ,  Peter Matyus ,  Andras Varro ,  Laszlo Szam ,  Sarolta Vegvari nee Gyurki

IPC分类号： A61K31/535 ,  A61K31/5383 ,  A61P9/00 ,  A61P9/04 ,  A61P9/08 ,  A61P9/10 ,  C07D498/04

CPC分类号： C07D498/04

摘要： The invention relates to novel pyrimido [5,4-b][1,4]oxazine derivatives of the formula (I), and the acid addition salts thereof, pharmaceutical compositions containing them and a process for their preparation. In the formula (I) ##STR1## wherein R.sup.1 stands for a C.sub.1-4 alkyl group;R.sup.2 stands for hydrogen or halogen or an azido group or an --NR.sup.5 R.sup.6 group, whereinR.sup.5 represents hydrogen or a benzyl group, or a C.sub.1-4 alkyl group unsubstituted or substituted by a hydroxyl group,R.sup.6 stands for hydrogen, an amino group, a C.sub.3-6 cycloalkyl group, a straight or branched-chain C.sub.1-4 alkyl group optionally substituted by a hydroxyl, mercapto, aminocarbonyl, furyl, 2-benzo[1,4]dioxanyl, di(C.sub.1-4 alkyl)amino group or by a phenyl or phenoxy group optionally mono- or polysubstituted by halogen or C.sub.1-4 alkoxy group (s) or by a 6-membered, saturated nitrogen-containing heterocycle optionally containing an additional nitrogen or oxygen atom and optionally substituted by a C.sub.1-4 alkyl or benzyl group; furtherNR.sup.5 R.sup.6 may also represents a 6-membered, saturated, nitrogen-containing heterocycle optionally containing an additional nitrogen or oxygen atom and optionally substituted by a C.sub.2-4 alkoxycarbonyl or C.sub.1-4 hydroxyalkyl group;R.sup.3 and R.sup.4 are the same or different and stand for hydrogen or a C.sub.1-4 alkyl group;R.sup.9 stands for hydrogen or a C.sub.1-4 alkyl group unsubstituted or monosubstituted by an oxo, cyano, aminocarbonyl, C.sub.2-5 alkoxycarbonyl, pyridiyl, morpholinocarbonyl, or phenyl group or mono- or polysubstituted by OH group(s), with the proviso that R.sup.2 is different from chlorine, 4-morpholinyl and piperidyl group when R.sup.9 stands for hydrogen; orR.sup.2 is different from chlorine and 4-morpholinyl group when R.sup.9 stands for a methyl or benzyl group.The compounds of the formula (I) are capable to increase the myocardial contractile force (the performance of the failing heart) and the coronary blood flow, thus they can therapeutically be used for the treatment of the chronic heart failure and coronary disturbances.

公开(公告)号：US4826845A

公开(公告)日：1989-05-02

申请号：US924445

申请日：1986-10-29

申请人： Endre Kasztreiner ,  Gyorgy Rablocsky ,  Nandor Makk ,  Laszlo Jaszlits ,  Peter Matyus ,  Gyorgy Cseh ,  Ildiko Pribusz nee Rapp ,  Klara Czako ,  Eszter Diesler ,  Istvan Elekes ,  Laszlo Kaufer ,  Maria Kuhar nee Kurthy ,  Judit Kincsessy ,  Judit Kosary ,  Gyongyi Nagy nee Csokas

发明人： Endre Kasztreiner ,  Gyorgy Rablocsky ,  Nandor Makk ,  Laszlo Jaszlits ,  Peter Matyus ,  Gyorgy Cseh ,  Ildiko Pribusz nee Rapp ,  Klara Czako ,  Eszter Diesler ,  Istvan Elekes ,  Laszlo Kaufer ,  Maria Kuhar nee Kurthy ,  Judit Kincsessy ,  Judit Kosary ,  Gyongyi Nagy nee Csokas

IPC分类号： C07D237/00 ,  A61K31/50 ,  A61K31/535 ,  A61P9/12 ,  C07D237/08 ,  C07D237/12 ,  C07D237/14 ,  C07D237/20 ,  C07D237/22 ,  C07D319/00 ,  C07D403/04 ,  C07D405/12 ,  C07D521/00 ,  C07D405/06

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D237/08 ,  C07D237/12 ,  C07D237/20 ,  C07D249/08 ,  C07D403/04 ,  C07D405/12

摘要： The invention relates to novel 3(2H)-pyridazinone-derivatives of the general formula (I), pharmaceutical compositions containing them and process for their preparation. In the general formula (I) ##STR1## stands for an ethyl or propyl group substituted by a terminal halogen atom or a hydroxyl or NR.sup.1 R.sup.2 group, whereinR.sup.1 represents hydrogen atom or an unsubstituted or optionally substituted benzyl group;R.sup.2 represents hydrogen atom or an unsubstituted or optionally substituted benzo[1,4]dioxan-2-yl-methyl or -ethyl group or a (CH.sub.2).sub.n --R.sup.3 group, whereinn is 2 or 3; andR.sup.3 stands for an unsubstituted or optionally substituted phenoxy or phenylthio group; andX stands for a hydrogen or halogen atom or an unsubstituted or optionally substituted, saturated or unsaturated 5- or 6-membered heterocyclic group containing a nitrogen atom and optionally an additional heteroatom, e.g. an oxygen, sulfur or nitrogen atom,with the proviso that R is different from an ethyl or propyl group substituted terminally by a hydroxyl group or halogen atom when X represents a hydrogen or chlorine atom.The compounds of general formula (I) selectively inhibit the adrenergic alpha.sub.1 receptors, have a calcium-antagonistic effect and exert blood pressure lowering action.

摘要翻译： 本发明涉及通式（I）的新的3（2H） - 哒嗪酮衍生物，含有它们的药物组合物及其制备方法。 在通式（I）中，（I）表示被末端卤素原子或羟基或NR 1 R 2基团取代的乙基或丙基，其中R 1表示氢原子或未取代或任意取代的苄基; R 2表示氢原子或未取代或任选取代的苯并[1,4]二氧杂环己烷-2-基 - 甲基或 - 乙基或（CH 2）n -R 3基团，其中n为2或3; R3代表未取代或任选取代的苯氧基或苯硫基; X代表氢或卤素原子，或未取代或任选取代的饱和或不饱和的含有氮原子和任选另外的杂原子的5或6元杂环基团。 氧，硫或氮原子，条件是当X表示氢或氯原子时，R不同于被羟基或卤素原子末端取代的乙基或丙基。 通式（I）的化合物选择性地抑制肾上腺素α1受体，具有钙拮抗作用并发挥降血压作用。

公开(公告)号：US5395934A

公开(公告)日：1995-03-07

申请号：US995295

申请日：1992-12-21

申请人： Peter Matyus ,  Klara Czako ,  Ildiko Varga ,  Andrea Jednakovics ,  Agnes Papp ,  Ilona Bodi ,  Gyorgy Rabloczky ,  Andras Varro ,  Laszlo Jaszlits ,  Aniko Miklos ,  Luca Levay ,  Gvorgy Schmidt ,  Marton Fekete ,  Maria Kurthy ,  Katalin Szemeredi ,  Erzsebet Zara

发明人： Peter Matyus ,  Klara Czako ,  Ildiko Varga ,  Andrea Jednakovics ,  Agnes Papp ,  Ilona Bodi ,  Gyorgy Rabloczky ,  Andras Varro ,  Laszlo Jaszlits ,  Aniko Miklos ,  Luca Levay ,  Gvorgy Schmidt ,  Marton Fekete ,  Maria Kurthy ,  Katalin Szemeredi ,  Erzsebet Zara

IPC分类号： A61K31/50 ,  A61K31/501 ,  A61K31/535 ,  A61K31/5377 ,  A61P9/06 ,  C07D237/14 ,  C07D237/22 ,  C07D403/04 ,  C07D403/06 ,  C07D413/06 ,  C07D413/14 ,  C07D237/10

CPC分类号： C07D237/14

摘要： Racemic or optically active new 3(2H)-pyridazinone derivatives, a process for the preparation thereof, pharmaceutical compositions comprising the same, to the use of the said 3(2H)-pyridazinone derivatives for the treatment of diseases and for the preparation of pharmaceutical compositions suitable for the treatment of diseases.The new 3(2H)-pyridazinone derivatives according to the invention correspond to the general formula (I), ##STR1##

摘要翻译： 外消旋或光学活性的新的3（2H） - 哒嗪酮衍生物，其制备方法，包含它们的药物组合物，使用所述3（2H） - 哒嗪酮衍生物用于治疗疾病和用于制备药物 适用于治疗疾病的组合物。 根据本发明的新的3（2H） - 哒嗪酮衍生物对应于通式（I），（I）

公开(公告)号：US4259328A

公开(公告)日：1981-03-31

申请号：US914778

申请日：1978-06-12

申请人： Geza Szilagyi ,  Endre Kasztreiner ,  Judit Kosary ,  Peter Matyus ,  Zsuzsa Huszti ,  Gyorgy Cseh ,  Agnes Kenessey ,  Laszlo Tardos ,  Edit Kosa ,  Laszlo Jaszlits ,  Sandor Elek ,  Istvan Elekes ,  Istvan Polgari

发明人： Geza Szilagyi ,  Endre Kasztreiner ,  Judit Kosary ,  Peter Matyus ,  Zsuzsa Huszti ,  Gyorgy Cseh ,  Agnes Kenessey ,  Laszlo Tardos ,  Edit Kosa ,  Laszlo Jaszlits ,  Sandor Elek ,  Istvan Elekes ,  Istvan Polgari

IPC分类号： A61K31/50 ,  A61P9/12 ,  C07D237/20 ,  C07D237/22 ,  C07D237/24 ,  C07D401/04 ,  C07D295/00 ,  A61K31/535

CPC分类号： C07D237/24 ,  C07D237/20 ,  C07D237/22

摘要： Pyridazinylhydrazones capable of lowering blood pressure having the formula ##STR1## wherein R.sup.1 is hydrogen, chlorine, alkyl having from 1 to 4 carbon atoms, methoxy, hydroxyl, carbamoyl or cyano;R.sup.2 is morpholino; andK is a group having the formula ##STR2## wherein one of R.sup.3, R.sup.4, R.sup.5 or R.sup.6 is carboxyl or alkoxycarbonyl.

摘要翻译： 能够降低血压的哒嗪基腙类具有下式：其中R1是氢，氯，具有1-4个碳原子的烷基，甲氧基，羟基，氨基甲酰基或氰基; R2是吗啉代; 并且K是具有式“IMAGE”的基团，其中R 3，R 4，R 5或R 6中的一个是羧基或烷氧基羰基。

公开(公告)号：US4308386A

公开(公告)日：1981-12-29

申请号：US89859

申请日：1979-10-31

申请人： Szilagyi Geza ,  Endre Kasztreiner ,  Judit Kosary ,  Peter Matyus ,  Zsuzsa Huszti ,  Gyorgy Cseh ,  Agnes Kenessey ,  Laszlo Tardos ,  Edit Kosa ,  Laszlo Jaszlits ,  Sandor Elek ,  Istvan Elekes ,  Istvan Polgari

发明人： Szilagyi Geza ,  Endre Kasztreiner ,  Judit Kosary ,  Peter Matyus ,  Zsuzsa Huszti ,  Gyorgy Cseh ,  Agnes Kenessey ,  Laszlo Tardos ,  Edit Kosa ,  Laszlo Jaszlits ,  Sandor Elek ,  Istvan Elekes ,  Istvan Polgari

IPC分类号： A61K31/50 ,  A61P9/12 ,  C07D237/20 ,  C07D237/22 ,  C07D237/24 ,  C07D401/04

CPC分类号： C07D237/24 ,  C07D237/20 ,  C07D237/22

摘要： Pyridazinylhydrazones capable of lowering blood pressure have the formula ##STR1## wherein R.sup.1 is hydrogen, chlorine, alkyl having from 1 to 4 carbon atoms, methoxy, hydroxyl, carbamoyl or cyano;R.sup.2 is chloro; andK is a group having the formula ##STR2## wherein one of R.sup.3, R.sup.4, R.sup.5 or R.sup.6 is carboxyl or alkoxycarbonyl.

摘要翻译： 能够降低血压的哒嗪基腙具有式“IMAGE”，其中R 1是氢，氯，具有1至4个碳原子的烷基，甲氧基，羟基，氨基甲酰基或氰基; R2是氯; 并且K是具有式“IMAGE”的基团，其中R 3，R 4，R 5或R 6中的一个是羧基或烷氧基羰基。

公开(公告)号：US4329457A

公开(公告)日：1982-05-11

申请号：US147224

申请日：1980-05-06

申请人： Geza Szilagyi ,  Peter Matyus ,  Endre Kasztreiner ,  Tibor Balogh ,  Lajos Ila

发明人： Geza Szilagyi ,  Peter Matyus ,  Endre Kasztreiner ,  Tibor Balogh ,  Lajos Ila

IPC分类号： A61K31/50 ,  A61P9/12 ,  C07D237/20 ,  C07D413/02

CPC分类号： C07D237/20

摘要： The invention relates to a novel process for the preparation of 6-(substituted amino)-3-pyridazinylhydrazines having the general formula I ##STR1## and their pharmaceutically acceptable acid addition salts, wherein R.sup.1 stands for hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms;R.sup.2 and R.sup.3 may be the same or different and stand for alkyl groups containing from 1 to 6 carbon atoms, alkenyl groups containing from 2 to 6 carbon atoms, hydroxyalkyl groups containing from 2 to 4 carbon atoms, cycloalkyl groups containing from 3 to 8 carbon atoms, phenyl or benzyl groups or phenyl, benzyl or phenylethyl groups containing one or two halogen atoms, nitro, methoxy or hydroxyl groups, and one of R.sup.2 and R.sup.3 may stand also for a hydrogen atom, or R.sup.2 and R.sup.3 together with the neighboring nitrogen atom may build up also a morpholino, pyrrolidino, piperidino, heptamethyleneimino or N-methylpiperazino group.The process consists in that a compound having the general formula II ##STR2## wherein R.sup.1 is as defined above, R.sup.4 stands for a chlorine or bromine atom or methylthio group, while A stands for a 1,7,7-trimethyl-2-bicyclo(2,2,1)heptylidene or a benzylidene group substituted by an R.sup.5 group, wherein R.sup.5 stands for hydrogen, chlorine or bromine atom, or a methoxy, nitro or methylsulphonyl group - is reacted with an amine having the general formula IIIR.sup.2 R.sup.3 NH (III)wherein R.sup.2 and R.sup.3 are as defined above - and the compound thus obtained having the general formula IV ##STR3## wherein R.sup.1, R.sup.2, R.sup.3 and A are as defined above - is subjected to acidic hydrolysis.The 6-(substituted amino)-3-pyridazinylhydrazines having the general formula I and prepared by the novel process of invention, possess a significant hypotensive effect as well as they are used as starting materials for the preparation of 6-(substituted amino)-3-pyridazinylhydrazines having a very significant hypotensive action.

公开(公告)号：US5854250A

公开(公告)日：1998-12-29

申请号：US908602

申请日：1997-08-08

申请人： Peter Matyus ,  Erzsebet Zara ,  Lajos Farkas ,  Agnes Papp ,  Antal Simay ,  Lajos Toldy ,  Ferenc Andrasi ,  Katalin Goldschmidt ,  Eszter Hodula ,  Ildiko Mathe ,  Klara Sutka ,  Zsuzsanna Fittler ,  Valeria Vitkoczi ,  Laszlo Sebestyen ,  Istvan Sziraki ,  Marta Rusz ,  Eva Gal

发明人： Peter Matyus ,  Erzsebet Zara ,  Lajos Farkas ,  Agnes Papp ,  Antal Simay ,  Lajos Toldy ,  Ferenc Andrasi ,  Katalin Goldschmidt ,  Eszter Hodula ,  Ildiko Mathe ,  Klara Sutka ,  Zsuzsanna Fittler ,  Valeria Vitkoczi ,  Laszlo Sebestyen ,  Istvan Sziraki ,  Marta Rusz ,  Eva Gal

IPC分类号： C07C235/60 ,  C07C237/22 ,  C07C259/06 ,  C07D207/26 ,  C07D207/263 ,  C07D239/50 ,  C07D295/185 ,  A61K31/495 ,  A61K31/505 ,  C07D241/04

CPC分类号： C07D207/27 ,  C07C235/60 ,  C07C237/22 ,  C07C259/06 ,  C07D239/50 ,  C07D295/185

摘要： An N-benzoylamino acid compound of the formula (I), ##STR1## wherein R.sup.3 is an NR.sup.4 R.sup.5 group where R.sup.4 and R.sup.5 which are the same or different are selected from the group consisting of hydrogen, a hydroxyl group, a C.sub.1-12 alkyl group, a C.sub.1-4 alkyl group substituted by a hydroxyl group and a C.sub.1-4 alkyl group substituted by an amino group; R.sup.4 and R.sup.5 when taken together with the adjacent nitrogen form a substituted or unsubstituted 5- or 6-membered heterocyclic group, a 5- or 6-membered heterocyclic group containing an additional nitrogen atom, a 5- or 6-membered heterocyclic group containing an additional nitrogen atom and being substituted by an oxo group, a phenyl-substituted C.sub.1-4 alkyl group or C.sub.3-5 alkenyl group; with the proviso that when the heterocyclic group is piperazine, this heterocyclic group may also be substituted by a diaminopyrimidinyl or di(pyrrolidino)-pyrimidinyl group; n is an integer from 2 to 15; and their tautomers, racemates and the pure optically active individual isomers or mixtures thereof, and a pharmaceutically acceptable salt thereof is described. These compounds are useful for the treatment of patients suffering from disorders being in an indirect or direct connection with pathological oxidation processes occurring in the organism, particularly ischaemic and reperfusion tissue injuries, inflammations, atherosclerosis, or degenerative neurological disorders.

摘要翻译： 式（I）的N-苯甲酰氨基酸化合物，其中R 3是NR 4 R 5基团，其中R 4和R 5相同或不同，选自氢，羟基，C 1-12烷基 基团，被羟基取代的C 1-4烷基和被氨基取代的C 1-4烷基; R 4和R 5与相邻的氮原子一起形成取代或未取代的5元或6元杂环基，含有另外的氮原子的5元或6元杂环基，含有 另外的氮原子被氧代基取代，苯基取代的C 1-4烷基或C 3-5烯基; 条件是当杂环基为哌嗪时，该杂环基也可以被二氨基嘧啶基或二（吡咯烷子基） - 嘧啶基取代; n为2〜15的整数。 及其互变异构体，外消旋体和纯的光学活性单体异构体或其混合物及其药学上可接受的盐。 这些化合物可用于治疗患有与生物体内发生的病理氧化过程间接或直接相关的疾病的患者，特别是缺血和再灌注组织损伤，炎症，动脉粥样硬化或退行性神经障碍。

公开(公告)号：US5705529A

公开(公告)日：1998-01-06

申请号：US540924

申请日：1995-10-11

申请人： Peter Matyus ,  Erzsebet Zara ,  Lajos Farkas ,  Agnes Papp ,  Antal Simay ,  Lajos Toldy ,  Ferenc Andrasi ,  Katalin Goldschmidt ,  Eszter Hodula ,  Ildiko Mathe ,  Klara Sutka ,  Zsuzsanna Fittler ,  Valeria Vitkoczi ,  Laszlo Sebestyen ,  Istvan Sziraki ,  Marta Rusz ,  Eva Gal

发明人： Peter Matyus ,  Erzsebet Zara ,  Lajos Farkas ,  Agnes Papp ,  Antal Simay ,  Lajos Toldy ,  Ferenc Andrasi ,  Katalin Goldschmidt ,  Eszter Hodula ,  Ildiko Mathe ,  Klara Sutka ,  Zsuzsanna Fittler ,  Valeria Vitkoczi ,  Laszlo Sebestyen ,  Istvan Sziraki ,  Marta Rusz ,  Eva Gal

IPC分类号： A61K31/165 ,  A61K31/19 ,  A61K31/215 ,  A61K31/505 ,  A61P3/06 ,  C07C231/02 ,  C07C235/52 ,  C07C235/60 ,  C07C237/22 ,  C07C259/06 ,  C07D207/26 ,  C07D207/263 ,  C07D239/50 ,  C07D295/185 ,  C07C229/14

CPC分类号： C07D207/27 ,  C07C235/60 ,  C07C237/22 ,  C07C259/06 ,  C07D239/50 ,  C07D295/185

摘要： The invention relates to novel N-benzoylamino acid derivatives of the general formula (I), ##STR1## wherein R.sup.1 and R.sup.2, which are the same or different, stand for a hydroxyl group optionally bearing an acetyl group; or a C.sub.1-6 alkoxy group optionally substituted by a phenyl group; n means an integer from 2 to 15 as well as their tautomers, racemates and optically active individual (pure) isomers or mixtures thereof and the salts of these compounds and pharmaceutical compositions containing these compounds. The invention relates also to a process for the preparation of compounds of the general formula (I). The compounds of general formula (I) inhibit the peroxidation of lipids and therefore, they are expected to be useful for the treatment of diseases being in an indirect or direct connection with pathological oxidation processes, chiefly for the treatment and/or prevention of ischaemic and reperfusion tissue injuries, inflammatory reactions, atherosclerosis, various degenerative neurological disorders as well as for delaying the natural process of the ageing of cells.

摘要翻译： 本发明涉及通式（I）的新型N-苯甲酰氨基酸衍生物，其中R1和R2相同或不同，代表任选带有乙酰基的羟基; 或任选被苯基取代的C 1-6烷氧基; n表示2至15的整数，以及它们的互变异构体，外消旋体和光学活性个体（纯）异构体或其混合物，以及这些化合物的盐和含有这些化合物的药物组合物。 本发明还涉及制备通式（I）化合物的方法。 通式（I）的化合物抑制脂质的过氧化，因此预期它们可用于治疗与病理氧化过程间接或直接相关的疾病，主要用于治疗和/或预防缺血和 再灌注组织损伤，炎症反应，动脉粥样硬化，各种退行性神经障碍以及延缓细胞老化的自然过程。

公开(公告)号：US06602865B1

公开(公告)日：2003-08-05

申请号：US09439847

申请日：1999-11-15

申请人： Ferenc Andrasi ,  Agnes Angyal nee Pataky ,  Pal Berzsenyi ,  Sandor Boros ,  Laszlo Harsing ,  Katalin Horvath ,  Peter Matyus ,  Imre Moravcsik ,  Agnes Papp nee Behr ,  Antal Simay ,  Erzsebet Szabo nee Bagdy ,  Katalin Szabo nee Pusztai ,  Istvan Tarnawa ,  Ildiko Varga

发明人： Ferenc Andrasi ,  Agnes Angyal nee Pataky ,  Pal Berzsenyi ,  Sandor Boros ,  Laszlo Harsing ,  Katalin Horvath ,  Peter Matyus ,  Imre Moravcsik ,  Agnes Papp nee Behr ,  Antal Simay ,  Erzsebet Szabo nee Bagdy ,  Katalin Szabo nee Pusztai ,  Istvan Tarnawa ,  Ildiko Varga

IPC分类号： A61K3155

CPC分类号： C07D513/04 ,  A61K31/55 ,  A61K31/551 ,  A61K31/553 ,  A61K31/554

摘要： Pyridazino(4,5-b)(1,5)oxazepinone, thiazepinone and diazepinone compounds of formula(I) and their tautomers and the acid-addition salts of all these compounds show memory-enhancing and neuroprotective properties.

摘要翻译： 式（I）的哒嗪（4,5-b）（1,5）恶唑酮，噻替酮和二氮杂酮化合物及其互变异构体和所有这些化合物的酸加成盐显示记忆增强和神经保护性质。