公开(公告)号：US4027024A

公开(公告)日：1977-05-31

申请号：US649237

申请日：1976-01-15

Applicant: Jozsef Knoll ,  Zsuzsanna Furst ,  Zoltan Meszaros ,  Peter Szentmiklosi ,  Agoston David ,  Istvan Hermecz ,  Attila Mandi ,  Rezso Bognar ,  Sandor Makleit ,  Gyula Valovics ,  Laszlo Szavik ,  Sandor Nagy

Inventor： Jozsef Knoll ,  Zsuzsanna Furst ,  Zoltan Meszaros ,  Peter Szentmiklosi ,  Agoston David ,  Istvan Hermecz ,  Attila Mandi ,  Rezso Bognar ,  Sandor Makleit ,  Gyula Valovics ,  Laszlo Szavik ,  Sandor Nagy

IPC: A61K31/655 ,  A61K31/485 ,  A61K31/505

CPC classification number: A61K31/655

Abstract: Pharmaceutical compositions of synergistic analgesic activity are provided which comprise an azido compound of the following formula: ##STR1## or a salt thereof wherein R is hydrogen, methyl, ethyl, acetyl or morpholino-methyl and a compound of the formula: ##STR2## wherein R.sup.1, R.sup.2, R.sup.3 are hydrogen or lower alkyl and the dotted lines represent hydrogenated bonds or olefinic bonds and pharmaceutically acceptable salts and quaternary salts thereof, in admixture with suitable inert solid or liquid carriers or dilutents.

Abstract translation: 提供协同镇痛活性的药物组合物，其包含下式的叠氮化合物：其中R是氢，甲基，乙基，乙酰基或吗啉代甲基的下式的化合物：其中 R1，R2，R3是氢或低级烷基，虚线代表氢化键或烯键及其药学上可接受的盐和季盐，与合适的惰性固体或液体载体或稀释剂混合。

公开(公告)号：US4035491A

公开(公告)日：1977-07-12

申请号：US700782

申请日：1976-06-29

Applicant: Jozsef Knoll ,  Zsuzsanna Furst ,  Zoltan Meszaros ,  Gabor Nagy ,  Agoston David ,  Rezso Bognar ,  Sandor Makleit ,  Gyula Valovics

Inventor： Jozsef Knoll ,  Zsuzsanna Furst ,  Zoltan Meszaros ,  Gabor Nagy ,  Agoston David ,  Rezso Bognar ,  Sandor Makleit ,  Gyula Valovics

IPC: A61K31/655 ,  A61K31/485 ,  A61K31/505

CPC classification number: A61K31/655

Abstract: A pharmaceutical composition with synergistic analgesic effect which comprises an effective amount of 6-desoxy-6-azido-14-hydroxy-7,8-dihydro morphine or codeine or an analgesically effective salt thereof and an effective amount of a compound ##STR1## wherein R.sup.1 and R.sup.2 are lower alkyl and R.sup.3 is hydrogen or lower alkyl, and the dotted lines represent hydrogenated or unsaturated bonds or an analgesically effective salt or quaternary compound thereof.

Abstract translation: 具有协同镇痛作用的药物组合物，其包含有效量的6-脱氧-6-叠氮基-14-羟基-7,8-二氢吗啡或可待因或其镇痛有效盐和有效量的化合物（IMAGE）（ II）其中R1和R2是低级烷基，R3是氢或低级烷基，虚线代表氢化或不饱和键或其镇痛有效的盐或季铵化合物。

公开(公告)号：US5232926A

公开(公告)日：1993-08-03

申请号：US957642

申请日：1992-10-06

Applicant: Sandor Hosztafi ,  Sandor Makleit ,  Laszlo Szilagyi ,  Kalmany Zsupan

Inventor： Sandor Hosztafi ,  Sandor Makleit ,  Laszlo Szilagyi ,  Kalmany Zsupan

IPC: C07D489/08

CPC classification number: C07D489/08

Abstract: The present invention relates to novel morphinane-skeletoned compounds of the formula (I) ##STR1## wherein Y in-NH phenyl or --NH dintro phenyl, Z is --CH.sub.2 -- CH.sub.2, R.sub.2 is hydroxyl and R.sub.3 is H or methyl, the steric isomers and the pharmaceutically acceptable salts thereof, a novel process for producing the same and pharmaceutical compositions comprising the same as active ingredients.The novel compounds can be used in the therapy as analgetic or morphine-antagonistic agents.

Abstract translation: 本发明涉及式（I）的新的吗啡烷骨架化合物其中Y为-NH苯基或-NH二苯基苯基，Z为-CH 2 -CH 2，R 2为羟基，R 3为H或甲基 ，空间异构体及其药学上可接受的盐，其制备方法和包含其的活性成分的药物组合物。 新化合物可用于治疗作为止痛或吗啡拮抗剂。

公开(公告)号：US4144236A

公开(公告)日：1979-03-13

申请号：US795443

申请日：1977-05-10

Applicant: Reszo Bognar ,  Sandor Makleit ,  Geza Kiss ,  Sandor Berenyi ,  Terez Mile ,  Jozsef Knoll ,  Sandor Elek ,  Istvan Gyoker ,  Attila Zoltai ,  Gyorgy Toth ,  Laszlo Litkei

Inventor： Reszo Bognar ,  Sandor Makleit ,  Geza Kiss ,  Sandor Berenyi ,  Terez Mile ,  Jozsef Knoll ,  Sandor Elek ,  Istvan Gyoker ,  Attila Zoltai ,  Gyorgy Toth ,  Laszlo Litkei

IPC: C07D489/00 ,  C07D489/02 ,  C07D489/08 ,  C07D489/06 ,  A61K31/485

CPC classification number: C07D489/00 ,  C07D489/02 ,  C07D489/08 ,  Y10S514/849

Abstract: A process for the preparation of pharmaceutically acceptable 3-protected derivatives of 6-deoxy-6-azido-14-hydroxy-7, 8-dihydroisomorphine, selected from the group which consists of 3-O-acetyl-6-deoxy-6-azido-14-hydroxy-7, 8-dihydroisomorphine, 3-O-tetrahydropyranyl-6-deoxy-6-azido-14-hydroxy-7, 8-dihydroisomorphine and 3-O-methylenemethoxy-6-deoxy-6-azido-14-hydroxy-7, 8-dihydroisomorphine, and the salts of these compounds which comprise the following steps:Blockin the hydroxy in position 3 of 14-hydroxy-7, 8-dihydromorphine with a moiety selected from the group which consists of acetyl, tetrahydropyranyl, and methylenemethoxy; andAzidiylating position 6 of the compounds formed in a step (a) thereby removing the hydroxy formerly in that position.

Abstract translation: 制备6-脱氧-6-叠氮基-14-羟基-7,8-二氢异吗啡的药学上可接受的3-保护的衍生物的方法，该衍生物选自由3-O-乙酰基-6-脱氧-6- 叠氮基-14-羟基-7,8-二氢异吗啡，3-O-四氢吡喃基-6-脱氧-6-叠氮基-14-羟基-7,8-二氢异吗啡和3-O-亚甲基甲氧基-6-脱氧-6-叠氮基 - 14-羟基-7,8-二氢异吗啡和这些化合物的盐，其包括以下步骤：

公开(公告)号：US3969519A

公开(公告)日：1976-07-13

申请号：US536402

申请日：1974-12-26

Applicant: Jozsef Knoll ,  Zsuzsanna Furst ,  Zoltan Meszaros ,  Gabor Nagy ,  Agoston David ,  Rezso Bognar ,  Sandor Makleit ,  Gyula Valovics

Inventor： Jozsef Knoll ,  Zsuzsanna Furst ,  Zoltan Meszaros ,  Gabor Nagy ,  Agoston David ,  Rezso Bognar ,  Sandor Makleit ,  Gyula Valovics

IPC: A61K31/655 ,  A61K31/505 ,  A61K31/485

CPC classification number: A61K31/655

Abstract: A pharmaceutical composition having synergistic analgesic effect which includes an azido compound of the formula: ##SPC1## namely an azido morphine or an azido codeine, and at least one compound of the formula: ##SPC2##The synergistic composition has been found to have less narcotic side effects than morphine and equal or better analgesic properties.

Abstract translation: 一种具有协同止痛效果的药物组合物，其包含下式的叠氮化合物：

公开(公告)号：US4511736A

公开(公告)日：1985-04-16

申请号：US456383

申请日：1983-01-07

Applicant: Ferenc Mogyorodi ,  Eniko Koppany ,  Tibor Bodi ,  Karoly Balogh ,  Istvan Toth ,  Rezso Bognar ,  Sandor Makleit ,  Gyorgy Litkei ,  Miklos Rakosi ,  Zoltan Dinya

Inventor： Ferenc Mogyorodi ,  Eniko Koppany ,  Tibor Bodi ,  Karoly Balogh ,  Istvan Toth ,  Rezso Bognar ,  Sandor Makleit ,  Gyorgy Litkei ,  Miklos Rakosi ,  Zoltan Dinya

IPC: C07C233/07 ,  A01N20060101 ,  A01N37/28 ,  C07C20060101 ,  C07C102/00 ,  C07C102/06

CPC classification number: C07C231/02 ,  A01N37/22

Abstract: The invention relates to a novel process for preparing chloroacetanilides of the formula ##STR1## wherein: R.sub.1 and R.sub.2 represent independently from each other a hydrogen atom or a C.sub.1-8 alkyl or C.sub.1-8 alkoxy group; andR.sub.3 stands for a straight chained or branched C.sub.1-8 alkoxy group.Said process is characterized by chloroacetylating a 2,6-dialkylaniline of the formula ##STR2## wherein R.sub.1 and R.sub.2 are as defined above, at a temperature of 10.degree. to 120.degree. C., optionally in a solvent medium in the presence of an acid binding agent, then reacting a thus-obtained intermediate with chloromethyl chloroformiate or, alternatively, reacting a compound of the formula (II) first with chloromethyl chloroformiate and subjecting then to chloroacetylation, thereafter reacting a thus-obtained intermediate with an alcohol of the formulaR.sub.3 --OH (III),wherein R.sub.3 is as defined above, optionally in a solvent medium in the presence of an acid binding agent, and recovering a product of the formula (I) in a known manner.The process of the invention enables the more simple and economic preparation of the compounds of formula (I) of improved purity.

Abstract translation: 本发明涉及一种制备式（I）的氯乙酰苯胺的新方法，其中：R1和R2彼此独立地表示氢原子或C1-8烷基或C1-8烷氧基; R3代表直链或支链C 1-8烷氧基。 所述方法的特征在于在10℃至120℃的温度下，任选在存在的溶剂介质中氯代乙酰化式（II）的2,6-二烷基苯胺，其中R 1和R 2如上定义 然后使由此获得的中间体与氯甲基氯甲酸酯反应，或者使式（II）的化合物首先与氯甲酸氯甲酯反应，然后进行氯乙酰化，然后使由此得到的中间体与醇的醇反应 任选地在酸性结合剂存在下在溶剂介质中，以已知方式回收式（I）的产物，其中R3如上所定义的式R3-OH（III）。 本发明的方法使得可以更简单和经济地制备具有改进纯度的式（I）化合物。

公开(公告)号：US4167636A

公开(公告)日：1979-09-11

申请号：US891195

申请日：1978-03-29

Applicant: Rezso Bognar ,  Sandor Makleit ,  Geza Kiss ,  Sandor Berenyi ,  Terez Mile ,  Jozsef Knoll ,  Sandor Elek ,  Istvan Gyoker ,  Attila Zoltai ,  Gyorgy Toth ,  Laszlo Litkei

Inventor： Rezso Bognar ,  Sandor Makleit ,  Geza Kiss ,  Sandor Berenyi ,  Terez Mile ,  Jozsef Knoll ,  Sandor Elek ,  Istvan Gyoker ,  Attila Zoltai ,  Gyorgy Toth ,  Laszlo Litkei

IPC: C07D489/00 ,  C07D489/02 ,  A61K31/485

CPC classification number: C07D489/02 ,  C07D489/00 ,  Y10S514/849

Abstract: Azidoethylmorphine, a new 7,8-dihydroisomorphine derivative, has excellent antitussive effects without respiration depression.

Abstract translation: 新的7,8-二氢异吗啡衍生物叠氮乙基吗啡具有无呼吸抑制的优异的镇咳作用。

公开(公告)号：US3954986A

公开(公告)日：1976-05-04

申请号：US415749

申请日：1973-11-14

Applicant: Jozsef Knoll ,  Zsuzsanna Furst ,  Zoltan Meszaros ,  Peter Szentmiklosi ,  Agoston David ,  Istvan Hermecz ,  Attila Mandi ,  Rezso Bognar ,  Sandor Makleit ,  Gyula Valovics ,  Laszlo Szlavik ,  Sandor Nagy

Inventor： Jozsef Knoll ,  Zsuzsanna Furst ,  Zoltan Meszaros ,  Peter Szentmiklosi ,  Agoston David ,  Istvan Hermecz ,  Attila Mandi ,  Rezso Bognar ,  Sandor Makleit ,  Gyula Valovics ,  Laszlo Szlavik ,  Sandor Nagy

IPC: A61K31/655 ,  A61K31/505 ,  A61K31/485

CPC classification number: A61K31/655

Abstract: An analgesic substitute for morphine comprising the synergistic combination of azidomorphine or azidocodeine with a pyrimidazolium.

Abstract translation: 吗啡的止痛剂替代物，其包含叠氮吗啡或叠氮基与佐剂的协同组合。