公开(公告)号：US4868184A

公开(公告)日：1989-09-19

申请号：US41233

申请日：1987-04-22

申请人： Edith Toth ,  Bela Kiss ,  Jozsef Torley ,  Eva Palosi ,  Istvan Hajdu ,  Laszlo Szporny ,  Dora Groo ,  Erzsebet Lapis ,  Istvan Laszlovszky

发明人： Edith Toth ,  Bela Kiss ,  Jozsef Torley ,  Eva Palosi ,  Istvan Hajdu ,  Laszlo Szporny ,  Dora Groo ,  Erzsebet Lapis ,  Istvan Laszlovszky

IPC分类号： C07D295/08 ,  A61K31/495 ,  A61P25/00 ,  A61P25/24 ,  A61P25/26 ,  C07D295/088

CPC分类号： C07D295/088

摘要： The invention relates to novel benzhydryl-piperazine derivatives of the general formula (I) and the acid addition and quaternary ammonium salts thereof, pharmaceutical compositions containing them and a process for their preparation. In the general formula (I) ##STR1## R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are the same or different and stand for hydrogen or halogen, or a trihalomethyl, C.sub.1-4 alkyl or C.sub.1-4 alkoxy group;R.sub.6 means hydrogen or a C.sub.1-4 alkyl group; andn is 2 or 3.The compounds of the general formula (I) are useful for treating diseases arising from a decrease in the dopamine level, i.e. from a hypofunction of the dopaminergic system, and have low toxicity.

摘要翻译： 本发明涉及通式（I）的新型二苯甲基 - 哌嗪衍生物及其酸加成盐和季铵盐，含有它们的药物组合物及其制备方法。 在通式（I）中，R 1，R 2，R 3，R 4和R 5相同或不同，代表氢或卤素，或三卤甲基，C 1-4烷基或C 1-4烷氧基; R6表示氢或C1-4烷基; n为2或3.通式（I）的化合物可用于治疗多巴胺水平降低引起的疾病，即多巴胺能系统的功能低下，毒性低。

公开(公告)号：US4874765A

公开(公告)日：1989-10-17

申请号：US41206

申请日：1987-04-22

申请人： Erzsebet Lapis ,  Edit Toth ,  Bela Kiss ,  Jozsef Torley ,  Eva Palosi ,  Istvan Hajdu ,  Laszlo Szporny ,  Dora Groo ,  Istvan Laszlovszky

发明人： Erzsebet Lapis ,  Edit Toth ,  Bela Kiss ,  Jozsef Torley ,  Eva Palosi ,  Istvan Hajdu ,  Laszlo Szporny ,  Dora Groo ,  Istvan Laszlovszky

IPC分类号： C07D295/08 ,  A61K31/495 ,  A61P25/00 ,  A61P25/24 ,  A61P25/26 ,  C07D295/088 ,  C07D295/18 ,  C07D295/185 ,  C07D295/10

CPC分类号： C07D295/185 ,  C07D295/088

摘要： The invention relates to novel 1,4-disubstituted piperazine derivatives of the general formula (I), pharmaceutically acceptable acid addition and quaternary ammonium salts thereof, pharmaceutical compositions containing them and a process for their preparation. In the general formula (I) ##STR1## R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are the same or different and stand for hydrogen or halogen or a trihalomethyl, lower alkyl, lower alkoxy, nitro, hydroxyl, aralkyloxy or an 1-(2-propenyl-4-piperazinyl) group;R.sub.5 stands for hydrogen or a C.sub.1-4 alkyl group;R.sub.6 represents a C.sub.3-6 alkyl, alkenyl, alkynyl group or a ##STR2## group, wherein R.sub.7 means a C.sub.2-5 alkyl, alkenyl or alkinyl group; andis 2 or 3,with the provisos that:R.sub.6 is different from isopropyl, n-butyl and isobutyl group when R.sub.2, R.sub.3, R.sub.4 and R.sub.5 stand for hydrogen, R.sub.1 means 2-chloro and n is 2;R.sub.6 is different from isopropyl group when R.sub.2, R.sub.3, R.sub.4 and R.sub.5 stand for hydrogen, R.sub.1 means 2-chloro and n is 2; or when R.sub.2, R.sub.3, R.sub.4 and R.sub.5 stand for hydrogen, R.sub.1 means 2-methyl group and n is 2; andR.sub.6 is different from propionyl group when R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are hydrogen and n means 2.The compounds of the general formula (I) are therapeutically useful for the treatment of diseases arising from a hypofunction of the dopaminergic system.

摘要翻译： 本发明涉及通式（I）的新的1,4-二取代哌嗪衍生物，其药学上可接受的酸加成盐和季铵盐，含有它们的药物组合物及其制备方法。 在通式（I）中，R 1，R 2，R 3和R 4相同或不同，代表氢或卤素或三卤代甲基，低级烷基，低级烷氧基，硝基，羟基，芳烷氧基或1- （2-丙烯基-4-哌嗪基）基团; R5代表氢或C1-4烷基; R6表示C3-6烷基，烯基，炔基或者IMAGE基团，其中R7表示C2-5烷基，烯基或炔基; 并且为2或3，条件是：当R 2，R 3，R 4和R 5代表氢时，R 6不同于异丙基，正丁基和异丁基，R 1表示2-氯且n为2; 当R2，R3，R4和R5代表氢时，R6不同于异丙基，R1表示2-氯，n是2; 或当R2，R3，R4和R5代表氢时，R1表示2-甲基，n表示2; 当R 1，R 2，R 3，R 4和R 5为氢且n表示2时，R 6与丙酰基不同。通式（I）的化合物可治疗用于治疗多巴胺能系统功能低下的疾病。

公开(公告)号：US5157038A

公开(公告)日：1992-10-20

申请号：US566274

申请日：1990-08-10

申请人： Edit Toth ,  Jozsef Torley ,  Bela Hegedus ,  Laszlo Szporny ,  Bela Kiss ,  Eva Palosi ,  Dora Groo ,  Istvan Laszlovszky ,  Erzsebet Lapis ,  Ferenc Auth ,  Laszlo Gaal

发明人： Edit Toth ,  Jozsef Torley ,  Bela Hegedus ,  Laszlo Szporny ,  Bela Kiss ,  Eva Palosi ,  Dora Groo ,  Istvan Laszlovszky ,  Erzsebet Lapis ,  Ferenc Auth ,  Laszlo Gaal

IPC分类号： A61K31/42 ,  A61K31/445 ,  A61K31/4465 ,  A61P3/00 ,  A61P25/00 ,  A61P43/00 ,  C07D211/48 ,  C07D491/10 ,  C07D491/107 ,  C07D491/113 ,  C07D493/10 ,  C07D498/10

CPC分类号： C07D491/10

摘要： The invention relates to novel 2-oxo-1-oxa-8-azaspiro[4,5]decane derivatives of the formula (I), ##STR1## wherein X means oxygen or an >NR group, whereinR stands for hydrogen; a C.sub.1-12 alkyl; C.sub.3-6 cycloalkyl; carbocyclic C.sub.6-10 aryl or carbocyclic C.sub.6-10 aryl-C.sub.1-4 alkyl group, the two latter two substituents optionally substituted on their aromatic moiety by one or more, same or different halogen, one or more C.sub.1-4 alkyl, C.sub.1-4 alkoxy or trihalomethyl group; or a tosyl group;R.sup.1 and R.sup.2 together represent a methylene group or, when X stands for an >NR group wherein R is as defined above, one of R.sup.1 and R.sup.2 m may represent a hydroxyl group and the other one is a methyl group; andR.sup.3 means hydrogen, benzyl, (C.sub.1-4 alkoxy)carbonyl, phenoxycarbonyl, benzyloxycarbonyl, formyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-(2-hydroxethyl)piperazin-1-ylcarbonyl, 2-chloro-3-nicotinoylcarbamoyl or C.sub.1-6 alkylcarbamoyl group,as well as their acid addition and quaternary ammonium salts.

公开(公告)号：US4866062A

公开(公告)日：1989-09-12

申请号：US41234

申请日：1987-04-22

申请人： Edit Toth ,  Bela Kiss ,  Jozsef Turley ,  Eva Palosi ,  Istvan Hajdu ,  Laszlo Szporny ,  Dora Groo ,  Erzsebet Lapis ,  Istvan Laszlovszky

发明人： Edit Toth ,  Bela Kiss ,  Jozsef Turley ,  Eva Palosi ,  Istvan Hajdu ,  Laszlo Szporny ,  Dora Groo ,  Erzsebet Lapis ,  Istvan Laszlovszky

IPC分类号： C07D295/08 ,  A61K31/495 ,  A61P25/00 ,  A61P25/24 ,  A61P25/26 ,  A61P43/00 ,  C07D295/088

CPC分类号： C07D295/088

摘要： The invention relates to novel 1,4-disubstituted piperazine derivatives of the general formula (I), pharmaceutically acceptable acid addition salts thereof, pharmaceutical compositions containing them and a process for their preparation.In the general formula (I) ##STR1## R.sub.1 and R.sub.2 are the same or different and stand for hydrogen or halogen or a lower alkyl, trihalomethyl or lower alkoxy group.The compounds of the general formula (I) are therapeutically useful for the treatment of diseases arising from a hypofunction of the dopaminergic system.

摘要翻译： 本发明涉及通式（I）的新的1,4-二取代哌嗪衍生物，其药学上可接受的酸加成盐，含有它们的药物组合物及其制备方法。 在通式（I）中，R 1和R 2相同或不同，代表氢或卤素或低级烷基，三卤代甲基或低级烷氧基。 通式（I）的化合物可用于治疗由多巴胺能系统功能低下引起的疾病。

公开(公告)号：US5132303A

公开(公告)日：1992-07-21

申请号：US566278

申请日：1990-08-10

申请人： Edit Toth ,  Jozsef Torley ,  Sandor Gorog ,  Laszlo Szporny ,  Bela Kiss ,  Eva Palosi ,  Dora Groo ,  Istvan Laszlovszky ,  Erzsebet Lapis ,  Ferenc Auth ,  Laszlo Gaal

发明人： Edit Toth ,  Jozsef Torley ,  Sandor Gorog ,  Laszlo Szporny ,  Bela Kiss ,  Eva Palosi ,  Dora Groo ,  Istvan Laszlovszky ,  Erzsebet Lapis ,  Ferenc Auth ,  Laszlo Gaal

IPC分类号： A61K31/42 ,  A61K31/445 ,  A61P25/18 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  C07D211/22 ,  C07D491/10 ,  C07D491/113 ,  C07D498/10

CPC分类号： C07D491/10

摘要： The invention relates to novel, therapeutically active 4-methylene-2-oxo-8-azaspiro[4,5]decane derivatives of the compound, ##STR1## wherein X means oxygen or an >NR group, whereinR stands for hydrogen, C.sub.1-12 alkyl, C.sub.3-6 cycloalkyl, carbocyclic C.sub.6-10 aryl or carbocyclic C.sub.6-10 arylC.sub.1-4 alkyl group, the latter two being optionally substituted on their aromatic moiety by one or more, same or different halogen(s) or one or more C.sub.1-4 alkyl group(s) or by one or more C.sub.1-4 alkoxy group(s);R.sup.3 and R.sup.4, which are the same or different, represent hydrogen, one or more halogen(s), C.sub.1-4 alkyl, C.sub.1-4 alkoxy, trihalomethyl group or hydroxyl group optionally esterified by a C.sub.1-4 alkanoic acid; andis 1 or 2,their isomers, solvates, hydrates, acid addition and quaternary ammonium salts.

公开(公告)号：US5132309A

公开(公告)日：1992-07-21

申请号：US566279

申请日：1990-08-10

申请人： Edit Toth ,  Jozsef Torley ,  Sandor Gorog ,  Laszlo Szporny ,  Bela Kiss ,  Eva Palosi ,  Dora Groo ,  Istvan Laszlovszky ,  Erzsebet Lapis ,  Ferenc Auth ,  Laszlo Haal

发明人： Edit Toth ,  Jozsef Torley ,  Sandor Gorog ,  Laszlo Szporny ,  Bela Kiss ,  Eva Palosi ,  Dora Groo ,  Istvan Laszlovszky ,  Erzsebet Lapis ,  Ferenc Auth ,  Laszlo Haal

IPC分类号： A61K31/42 ,  A61K31/445 ,  A61P25/18 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  C07D211/22 ,  C07D491/10 ,  C07D491/113 ,  C07D498/10

CPC分类号： C07D491/10

摘要： The invention relates to, therapeutically active 2-oxo-3,8-diazaspiro[4,5]decane derivatives (I), ##STR1## wherein R means hydrogen, a C.sub.1-12 alkyl, C.sub.3-6 cycloalkyl, carbocyclic C.sub.6-10 aryl or carbocyclic C.sub.6-10 aryl-C.sub.1-4 alkyl group, the latter two optionally being substituted on their aromatic moiety by one or more, same or different halogen(s) or one or more C.sub.1-4 alkyl or C.sub.1-4 alkoxy group(s);one of R.sup.1 and R.sup.2 stands for a hydroxyl group whereas the other means a methyl gorup;R.sup.3 and R.sup.4, which are the same or different, represent hydrogen, one or more halogen(s), C.sub.1-4 alkyl, C.sub.1-4 alkoxy, trihalomethyl group or a hydroxyl group optionally esterified by a C.sub.1-4 alkanoic acid; andn is 1 or 2,their isomers, solvates, hydrates, acid addition and quaternary ammonium salts.

公开(公告)号：US4859682A

公开(公告)日：1989-08-22

申请号：US40938

申请日：1987-04-21

申请人： Tibor Keve ,  Gabor Megyeri ,  Bela Stefko ,  Lajos Kovacs, Jr. ,  Anna Kassai nee Zieger ,  Bela Kiss ,  Istvan Laszlovszky ,  Erzsebet Lapis ,  Eva Palosi ,  Dora Groo ,  Laszlo Szporny

发明人： Tibor Keve ,  Gabor Megyeri ,  Bela Stefko ,  Lajos Kovacs, Jr. ,  Anna Kassai nee Zieger ,  Bela Kiss ,  Istvan Laszlovszky ,  Erzsebet Lapis ,  Eva Palosi ,  Dora Groo ,  Laszlo Szporny

IPC分类号： A61K31/48 ,  A61P9/00 ,  A61P25/18 ,  C07D457/02

CPC分类号： C07D457/02

摘要： The invention relates to novel 2-halogenated 8- and 1,8-substituted ergolene 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 X stands for a halogen;R stands for a C.sub.1-4 alkyl group andR" means a hydroxyl group; orR stands for an acyl or substituted acyl group andR" represents a halogen or an --OR' group, whereinR' stands for an acyl or substituted acyl group; orR stands for hydrogen andR" means a halogen or an --OR' group, wherein R' stands for an acyl or substituted acyl group; and the dotted line means a double bond between the 8-9 or 9-10 positions.The compounds of the formula (I) possess an antipsychotic and antihypoxic action and a negligable extrapyramidal side-effect.

摘要翻译： 本发明涉及式（I）的新型2-卤代8-和1,8-取代的麦角烯衍生物及其酸加成盐，含有它们的药物组合物及其制备方法。 在式（I）中，其中X代表卤素; R代表C 1-4烷基，R“表示羟基; 或R表示酰基或取代的酰基，R“表示卤素或-OR'基团，其中R'表示酰基或取代的酰基; 或R表示氢，R“表示卤素或-OR'基团，其中R'表示酰基或取代的酰基; 虚线表示8-9或9-10位之间的双键。 式（I）的化合物具有抗精神病和抗低氧作用和可忽略的锥体束外副作用。

公开(公告)号：US4681887A

公开(公告)日：1987-07-21

申请号：US877298

申请日：1986-06-23

申请人： Gabor Megyeri ,  Tibor Keve ,  Bela Stefko ,  Erik Bogsch ,  Janos Galambos ,  Anna Kassainee Zieger ,  Ferenc Trischler ,  Eva Palosi ,  Dora Groo ,  Egon Karpati ,  Zsolt Szombathelyi ,  Laszlo Szporny ,  Bela Kiss ,  Istvan Laszlovszky ,  Erzsebet Lapis

发明人： Gabor Megyeri ,  Tibor Keve ,  Bela Stefko ,  Erik Bogsch ,  Janos Galambos ,  Anna Kassainee Zieger ,  Ferenc Trischler ,  Eva Palosi ,  Dora Groo ,  Egon Karpati ,  Zsolt Szombathelyi ,  Laszlo Szporny ,  Bela Kiss ,  Istvan Laszlovszky ,  Erzsebet Lapis

IPC分类号： A61K31/48 ,  A61P25/18 ,  A61P25/20 ,  A61P43/00 ,  C07D457/02 ,  A61K31/44

CPC分类号： A61K31/48 ,  C07D457/02

摘要： The invention relates to pharmaceutical compositions with a neuroleptic action as well as to a process for preparing these compositions.The active ingredients of the compositions of the invention are 2-halo-6-methyl-9-ergolene derivatives of the formula (I), ##STR1## wherein X represents a chlorine, bromine or iodine atom as well as their acid addition salts.The compositions of the invention contain an effective dose of compound of the general formula (I) or an acid addition salt thereof.

摘要翻译： 本发明涉及具有精神抑制作用的药物组合物以及制备这些组合物的方法。 本发明组合物的活性成分是式（I）的2-卤代-6-甲基-9-麦角烯衍生物，其中X代表氯，溴或碘原子，以及它们的酸 加成盐。 本发明的组合物含有有效剂量的通式（I）化合物或其酸加成盐。

公开(公告)号：US5118687A

公开(公告)日：1992-06-02

申请号：US566275

申请日：1990-08-10

申请人： Edit Toth ,  Jozsef Torley ,  Laszlo Szporny ,  Bela Kiss ,  Egon Karpati ,  Eva Palosi ,  Dora Groo ,  Istvan Laszlovszky ,  Zsolt Szombathelyi ,  Adam Sarkadi ,  Aniko Gere ,  Katalin Csomor ,  Mihaly Bodo ,  Judit Laszy ,  Zsolt Szentirmay

发明人： Edit Toth ,  Jozsef Torley ,  Laszlo Szporny ,  Bela Kiss ,  Egon Karpati ,  Eva Palosi ,  Dora Groo ,  Istvan Laszlovszky ,  Zsolt Szombathelyi ,  Adam Sarkadi ,  Aniko Gere ,  Katalin Csomor ,  Mihaly Bodo ,  Judit Laszy ,  Zsolt Szentirmay

IPC分类号： A61K31/33 ,  A61K31/335 ,  A61K31/42 ,  A61K31/435 ,  A61K31/445 ,  A61P3/00 ,  A61P9/00 ,  A61P9/10 ,  A61P25/28 ,  C07D221/00 ,  C07D263/00 ,  C07D317/00 ,  C07D491/10 ,  C07D491/107 ,  C07D491/113 ,  C07D493/10 ,  C07D498/10

CPC分类号： C07D491/10

摘要： The invention relates to novel compounds 1-oxa-2-oxo-8- of the formula (I), ##STR1## wherein X means oxygen or an >NR group, whereinR stands for hydrogen, a C.sub.1-12 alkyl, C.sub.3-6 cycloalkyl, carbocyclic C.sub.6-10 aryl or carbocyclic C.sub.6-10 aryl-C.sub.10-4 alkyl group, the latter two groups are optionally substituted on their aromatic moiety by one or more, same or different halogen(s), one or more C.sub.1-4 alkyl or C.sub.1-4 alkoxy group(s);R.sup.1 and R.sup.2 together represent a methylene group or, when X stands for an >NR group, wherein R is as defined above, one of R.sup.1 and R.sup.2 may represent a hydroxyl group whereas the other is a methyl group;R.sup.3 stands for hydrogen or a phenyl group optionally substituted by one or more halogen(s), one or more C.sub.1-4 alkyl or C.sub.1-4 alkoxy or hydroxyl group(s);R.sup.4 means hydrogen, one or more halogen(s), C.sub.1-4 alkyl, C.sub.1-4 alkoxy, hydroxyl or trihalomethyl group(s); andn is 1, 2 or 3as well as their acid addition and quaternary ammonium salts.

公开(公告)号：US4753949A

公开(公告)日：1988-06-28

申请号：US877294

申请日：1986-06-23

申请人： Gabor Megyeri ,  Tibor Keve ,  Bala Stefko ,  Erik Bogsch ,  Janos Galambos ,  Anna Kassi nee Zieger ,  Ferenc Trischler ,  Eva Palosi ,  Dora Groo ,  Egon Karpati ,  Zsolt Szombathelyi ,  Laszlo Szporny ,  Bela Kiss ,  Istvan Laszlovszky ,  Erzsebet Lapis

发明人： Gabor Megyeri ,  Tibor Keve ,  Bala Stefko ,  Erik Bogsch ,  Janos Galambos ,  Anna Kassi nee Zieger ,  Ferenc Trischler ,  Eva Palosi ,  Dora Groo ,  Egon Karpati ,  Zsolt Szombathelyi ,  Laszlo Szporny ,  Bela Kiss ,  Istvan Laszlovszky ,  Erzsebet Lapis

IPC分类号： A61K31/48 ,  A61P3/00 ,  A61P3/14 ,  A61P9/00 ,  A61P25/02 ,  A61P25/28 ,  C07D457/02

CPC分类号： C07D457/02

摘要： The invention relates to a novel process for the preparation of partially new 2-halonicergoline derivatives of the formula (I), ##STR1## wherein X stands for chlorine, bromine or iodine atom, as well as their acid addition salts.The process of the invention comprises esterifying a novel 2-halo-1-methyllumilysergol of the formula (II), ##STR2## wherein X is the same as defined above, or an acid addition salt thereof and, if desired, converting the thus-obtained 2-halonicergoline derivative of the formula (I) to an acid addition salt.The compounds of the invention improve the cognitive function of the brain and show an antihypoxic as well as a strong .alpha.-adrenerg blocking and calcium-antagonistic action.

摘要翻译： 本发明涉及制备式（I）的部分新的2-卤代麦角灵衍生物的新方法，其中X代表氯，溴或碘原子，以及它们的酸加成盐。 本发明的方法包括酯化式（II）的新的2-卤代-1-甲基烯丙基谷维素，其中X与上述定义相同，或其酸加成盐，如果需要，转化 将由此获得的式（I）的2-卤代麦角灵衍生物与酸加成盐反应。 本发明的化合物改善了脑的认知功能，并且显示出抗低氧以及强的α-肾上腺素能阻断和钙拮抗作用。