公开(公告)号：WO2007137593A1

公开(公告)日：2007-12-06

申请号：PCT/EE2007/000009

申请日：2007-05-25

Applicant: TALLINN UNIVERSITY OF TECHNOLOGY ,  AS VÄHIUURINGUTE TEHNOLOOGIA ARENDUSKESKUS ,  AS PROSYNTEST ,  LOPP, Margus ,  PAJU, Anne ,  EEK, Margus ,  LAOS, Marit ,  PEHK, Tõnis ,  JÄÄLAID, Raissa

Inventor： LOPP, Margus ,  PAJU, Anne ,  EEK, Margus ,  LAOS, Marit ,  PEHK, Tõnis ,  JÄÄLAID, Raissa

IPC: C07C69/738 ,  C07D307/33

CPC classification number: C07C69/738 ,  C07C2601/10 ,  C07D307/33

Abstract: Archiral (2-hydroxy-3-oxo-cyclopent-1-enyl) acetic acid) alkyl, alkylphenyl and phenyl esters, and a simple and efficient method for the synthesis of both enantiomers of homocitric acid gamma-lactone and the corresponding salts from these esters are described. The method is based on asymmetric oxidation of esters, and the steps of basic and acidic hydrolysis and final acidic lactonization of the homocitric acid into homocitric acid gamma-lactone. The homocitric acid salts are obtained after basic treatment of homocitric acid gamma-lactone. The esters, conditions and reagents used in chemical conversion and separating products are important constituents affording efficient and simple method for production of homocitric acid gamma-lactone and homocitric acid salts.

Abstract translation: 丙酮（2-羟基-3-氧代 - 环戊-1-烯基）乙酸）烷基，烷基苯基和苯基酯，以及用于合成高柠檬酸γ-内酯和它们的相应盐的两种对映异构体的简单而有效的方法 酯描述。 该方法基于酯的不对称氧化，以及将高酸性碱性和酸性水解和最终酸性内酯化为高柠檬酸γ-内酯的步骤。 在高碱性γ-内酯进行碱处理后得到高氯酸盐。 化学转化和分离产物中使用的酯，条件和试剂是提供生产高立高酸γ-内酯和高磷酸盐的有效和简单方法的重要成分。

公开(公告)号：WO2016003919A8

公开(公告)日：2016-01-07

申请号：PCT/US2015/038349

申请日：2015-06-29

Applicant: TEVA PHARMACEUTICAL INDUSTRIES LTD. ,  TEVA PHARMACEUTICALS USA, INC. ,  SCHMIDT, Malle ,  PÄRI, Malle ,  LAOS, Marit ,  MAASALU, Ants ,  KALJUSTE, Kalle

Inventor： SCHMIDT, Malle ,  PÄRI, Malle ,  LAOS, Marit ,  MAASALU, Ants ,  KALJUSTE, Kalle

IPC: A61K31/451

Abstract: This invention provides an isolated compound having the structure: The invention also provides for a process for preparing 4-(3-(methylsulfonyl)phenyl)-1-propylpiperidin-4-ol, 1-(3,3-bis(3-(methylsulfonyl)phenyl)propyl)-4-(3-(methylsulfonyl) phenyl)piperidone, 1,4-bis((3-(1 -propylpiperidin-4-yl)phenyl)sulfonyl)butane, (3R,4S)-4-(3-(methylsulfonyl)phenyl)-1-propylpiperidin-3-ol, 4-(3-(methylsulfonyl)phenyl)-l-propylpiperidine 1- oxide, 1-(2-methylpentyl)-4-(3-(methylsulfonyl)phenyl)piperidine, 4-(3-(methylsulfinyl)phenyl)-1-propyl-1,2,3,6-tetrahydropyridine, and 4-(3-(methylsulfonyl)phenyl)-1-propyl-1,2,3,6-tetrahydropyridine. This invention also provides an impurity or a salt thereof for use, as a reference standard to detect trace amounts of the impurity in a pharmaceutical composition comprising pridopidine or a pharmaceutically acceptable salt thereof. This invention further provides a process for producing a pridopidine drug product comprising obtaining a pridopidine drug substance and mixing the pridopidine drug substance with suitable excipients so as to produce the pridopidine drug product. This invention also provides a process for producing a pridopidine drug product. This invention also provides a process of distributing a pridopidine drug product.

公开(公告)号：WO2016003919A1

公开(公告)日：2016-01-07

申请号：PCT/US2015/038349

申请日：2015-06-29

Applicant: TEVA PHARMACEUTICAL INDUSTRIES LTD. ,  TEVA PHARMACEUTICALS USA, INC. ,  SCHMIDT, Malle ,  PÄRI, Malle ,  LAOS, Marit ,  MAASALU, Ants ,  KALJUSTE, Kalle

Inventor： SCHMIDT, Malle ,  PÄRI, Malle ,  LAOS, Marit ,  MAASALU, Ants ,  KALJUSTE, Kalle

IPC: A61K31/451

CPC classification number: A61K31/451 ,  C07D211/24 ,  C07D211/42 ,  C07D211/52 ,  G01N30/88 ,  G01N2030/8872

Abstract: This invention provides an isolated compound having the structure: The invention also provides for a process for preparing 4-(3-(methylsulfonyl)phenyl)-1-propylpiperidin-4-ol, 1-(3,3-bis(3-(methylsulfonyl)phenyl)propyl)-4-(3-(methylsulfonyl) phenyl)piperidone, 1,4-bis((3-(1 -propylpiperidin-4-yl)phenyl)sulfonyl)butane, (3R,4S)-4-(3-(methylsulfonyl)phenyl)-1-propylpiperidin-3-ol, 4-(3-(methylsulfonyl)phenyl)-l-propylpiperidine 1- oxide, 1-(2-methylpentyl)-4-(3-(methylsulfonyl)phenyl)piperidine, 4-(3-(methylsulfinyl)phenyl)-1-propyl-1,2,3,6-tetrahydropyridine, and 4-(3-(methylsulfonyl)phenyl)-1-propyl-1,2,3,6-tetrahydropyridine. This invention also provides an impurity or a salt thereof for use, as a reference standard to detect trace amounts of the impurity in a pharmaceutical composition comprising pridopidine or a pharmaceutically acceptable salt thereof. This invention further provides a process for producing a pridopidine drug product comprising obtaining a pridopidine drug substance and mixing the pridopidine drug substance with suitable excipients so as to produce the pridopidine drug product. This invention also provides a process for producing a pridopidine drug product. This invention also provides a process of distributing a pridopidine drug product.

Abstract translation: 本发明提供具有以下结构的分离的化合物：本发明还提供了制备4-（3-（甲基磺酰基）苯基）-1-丙基哌啶-4-醇，1-（3,3-双（3-（ 甲基磺酰基）苯基）丙基）-4-（3-（甲基磺酰基）苯基）哌啶酮，1,4-双（（3-（1-丙基哌啶-4-基）苯基）磺酰基）丁烷，（3R，4S） - （3-（甲基磺酰基）苯基）-1-丙基哌啶-3-醇，4-（3-（甲基磺酰基）苯基）-1-丙基哌啶1-氧化物，1-（2-甲基戊基）-4-（3- 甲基磺酰基）苯基）哌啶，4-（3-（甲基亚磺酰基）苯基）-1-丙基-1,2,3,6-四氢吡啶和4-（3-（甲基磺酰基）苯基）-1-丙基-1,2 ，3,6四氢吡啶。 本发明还提供了一种杂质或其盐作为用于检测药物组合物中微量杂质的参考标准，其包含派多啶或其药学上可接受的盐。 本发明进一步提供了一种制备哌多啶药物产品的方法，包括获得一种派多凡定药物，并将该丙泊德吡啶药物与合适的赋形剂混合，从而产生格列方啶药物。 本发明还提供了制备格列方啶药物的方法。 本发明还提供了分布丙泊德苷药物的方法。