公开(公告)号：WO2009067960A2

公开(公告)日：2009-06-04

申请号：PCT/CZ2008/000136

申请日：2008-11-05

Applicant: ZENTIVA, A.S. ,  STEPANKOVA, Hana ,  HAJICEK, Josef ,  SLAVIKOVA, Marketa ,  ZEZULA, Josef

Inventor： STEPANKOVA, Hana ,  HAJICEK, Josef ,  SLAVIKOVA, Marketa ,  ZEZULA, Josef

IPC: C07C251/24 ,  C07D205/08 ,  C07D407/06 ,  C07D413/06

CPC classification number: C07C251/24 ,  C07D205/08 ,  C07D405/06 ,  C07D413/06 ,  Y02P20/55

Abstract: A method of manufacturing (3 R ,4 S )-l-(4-fluorophenyl)-3-[(3 S )-3-(4-fluorophenyl)-3- hydroxypropyl)]-4-(4-hydroxyphenyl)-2-azetidinone (ezetimibe) of formula I, in which a protected ketone of general formula II, wherein R stands for a protective group, such as benzyloxycarbonyl, tert -butoxycarbonyl, benzhydryl or trityl, is reduced with asymmetrical borane agents in an inert organic solvent in the temperature range of -30 to +40 °C, and finally the obtained protected alcohol of general formula III, wherein R has the same meaning as above, is deprotected by the action of hydro genolytic or acidic agents in an inert organic solvent.

Abstract translation: 制备（3R，4S）-1-（4-氟苯基）-3 - [（3S）-3-（4-氟苯基）-3-羟丙基）] - 4-（4-羟基苯基）-2-氮杂环丁酮 （ezetimibe）其中R代表保护基团的通式II的受保护酮如苄氧羰基，叔丁氧基羰基，二苯甲基或三苯甲基，在不饱和硼烷试剂中在惰性有机溶剂中还原 -30℃〜+ 40℃的温度范围内，最后得到的通式III的保护醇，其中R具有与上述相同的含义，在惰性有机溶剂中由氢解酸或酸性剂的作用脱保护。

公开(公告)号：WO2009006859A2

公开(公告)日：2009-01-15

申请号：PCT/CZ2008/000079

申请日：2008-07-08

Applicant: ZENTIVA A.S. ,  STEPANKOVA, Hana ,  HAJICEK, Josef

Inventor： STEPANKOVA, Hana ,  HAJICEK, Josef

CPC classification number: C07D495/02

Abstract: A method of manufacturing 5-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4,5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl acetate, known under the INN name prasugrel of formula (I), in which the substance of formula (VI) is reacted with a cyclopropyl magnesium halide to produce the substance of formula (V), which reacted with methanesulfonyl chloride to give the methanesulfonate of formula (IV), which is further reacted with the compound of formula (III) to be converted the substance of formula (II) and the latter is converted to the substance of formula (I) with an acetylation agent.

Abstract translation: 制备5- [2-环丙基-1-（2-氟苯基）-2-氧代乙基] -4,5,6,7-四氢噻吩并[3,2-c]吡啶-3-酮的方法， （I）的INN名称普拉格雷已知其中式（VI）的物质与环丙基卤化镁反应以产生式（V）的物质，其与甲磺酰氯反应得到 （IV）的甲磺酸盐，其进一步与式（III）的化合物反应以转化为式（II）的物质，并且后者用乙酰化剂转化为式（I）的物质。 p>

公开(公告)号：WO2008104135A1

公开(公告)日：2008-09-04

申请号：PCT/CZ2008/000022

申请日：2008-02-25

Applicant: ZENTIVA, A.S. ,  VOSLAR Michal ,  ZATOPKOVA Monika ,  PETRICKOVA Hana ,  TISOVSKA Lucie

Inventor： VOSLAR Michal ,  ZATOPKOVA Monika ,  PETRICKOVA Hana ,  TISOVSKA Lucie

IPC: C07D413/06

CPC classification number: C07D413/06

Abstract: A method for the preparation of zolmitriptan or its pharmaceutically acceptable salts, comprising isolation of a crystalline salt of zolmitriptan, its optional re-purification and conversion to the substance of formula (III). Zolmitriptan hydrochloride in the crystalline state.

Abstract translation: 制备佐米曲坦或其药学上可接受的盐的方法，包括分离佐米曲坦的结晶盐，其任选的再纯化和转化为式（III）物质。 盐酸佐米曲坦在结晶状态。

公开(公告)号：WO2008083635A1

公开(公告)日：2008-07-17

申请号：PCT/CZ2008/000002

申请日：2008-01-08

Applicant: ZENTIVA, A.S. ,  HALAMA, Ales ,  JIRMAN, Josef

Inventor： HALAMA, Ales ,  JIRMAN, Josef

IPC: C07D215/18 ,  C07D323/00

CPC classification number: C07D215/18 ,  C07D323/00

Abstract: A method of preparation of Montelukast of formula (I) by reaction of the compound of formula (III) and a compound of formula (IX), characterized in that the reaction is carried out in the presence of a base, an inert solvent and a component increasing selectivity of the process, especially of a polyether of general formula (XIII), wherein R stands for hydrogen or an alkyl and the value of n varies from 1 to 40, polyethyleneglycol of general formula (XIV), wherein n=l to 40 or a crown-ether of formulae (XV), (XVI) or (XVII).

Abstract translation: 通过式（III）化合物和式（IX）化合物的反应制备式（I）孟鲁司特的方法，其特征在于该反应在 （其中R代表氢或烷基并且n的数值在1至40之间变化），通式（XIII）的聚乙二醇，通式（XIII）的聚乙二醇， XIV），其中n = 1至40或式（XV），（XVI）或（XVII）的冠醚。

公开(公告)号：WO2007048361A1

公开(公告)日：2007-05-03

申请号：PCT/CZ2006/000073

申请日：2006-10-25

Applicant: ZENTIVA, A.S. ,  RADL, Stanislav ,  STACH, Jan

Inventor： RADL, Stanislav ,  STACH, Jan

IPC: C07D403/10 ,  C07D405/14

CPC classification number: C07D403/10 ,  C07D405/14 ,  Y02P20/55

Abstract: A method of removing the triphenylmethane protecting group from precursors of antihypertensive drugs of general formula I, wherein R is a metabolically degradable group, B is a heterocyclic moiety with one or two 5- or 6-membered rings at least one of which contains two nitrogen heteroatoms, in which the compound of formula I is reacted with water in the presence of a solvent which is partially or completely miscible with water.

Abstract translation: 从通式I的抗高血压药物的前体除去三苯甲烷保护基团的方法，其中R是可代谢降解的基团，B是具有一个或两个5-或6-元环的杂环部分，其中至少一个含有两个氮 杂原子，其中式I化合物在与水部分或完全混溶的溶剂的存在下与水反应。

公开(公告)号：WO2007028347A2

公开(公告)日：2007-03-15

申请号：PCT/CZ2006/000056

申请日：2006-09-05

Applicant: ZENTIVA, A.S. ,  ETRYCH, Tomas ,  CHYTIL, Petr ,  STUDENOVSKY, Martin ,  PECHAR, Michal ,  ULBRICH, Karel ,  RIHOVA, Blanka

Inventor： ETRYCH, Tomas ,  CHYTIL, Petr ,  STUDENOVSKY, Martin ,  PECHAR, Michal ,  ULBRICH, Karel ,  RIHOVA, Blanka

IPC: A61K47/48

CPC classification number: A61K47/58

Abstract: A method for the preparation of polymeric conjugates of N-(2- hydroxypropyl)methacrylamide and a methacryloylaminoacylhydrazone of doxorubicin with pH-controlled release of the drug, comprising the following three steps of synthesis: a. preparation of a monomeric methacryloylaminoacylhydrazine, wherein the aminoacyl is derived from an amino acid or oligopeptide, by reaction of a methacryloyl halide with the respective peptide, amino acid, or a derivative thereof, and subsequent hydrazinolysis, b. synthesis of a polymeric precursor by direct copolymerization of N-(2- hydroxypropyl)methacrylamide with the methacryloylaminoacylhydrazine, and c. binding of doxorubicin to the polymeric precursor by reaction thereof with doxorubicin hydrochloride.

Abstract translation: 一种制备N-（2-羟基丙基）甲基丙烯酰胺和多柔比星的甲基丙烯酰基氨基酰腙与pH控制释放药物的聚合物共轭物的方法，包括以下三个合成步骤：a。 b。通过甲基丙烯酰卤与相应的肽，氨基酸或其衍生物的反应以及随后的肼解解，制备单体甲基丙烯酰氨基酰肼，其中氨酰基衍生自氨基酸或寡肽。 通过N-（2-羟丙基）甲基丙烯酰胺与甲基丙烯酰氨基酰肼的直接共聚合成聚合物前体，和c。 通过与多柔比星盐酸盐的反应将多柔比星与聚合物前体结合。

公开(公告)号：WO2005082915A1

公开(公告)日：2005-09-09

申请号：PCT/CZ2005/000024

申请日：2005-02-28

Applicant: ZENTIVA, A.S. ,  RICHER, Jindrich ,  JIRMAN, Josef ,  PETRICKOVA, Hana

Inventor： RICHER, Jindrich ,  JIRMAN, Josef ,  PETRICKOVA, Hana

IPC: C07F9/58

CPC classification number: C07F9/582

Abstract: The monosodium salt of 3-pyridyl-1-hydroxyethylidene-1,1-bisphosphonic acid in new amorphous forms, methods of preparation and a pharmaceutical formulation.

Abstract translation: 新的无定形形式的3-吡啶基-1-羟基亚乙基-1,1-二膦酸的单钠盐，制备方法和药物制剂。

公开(公告)号：WO2005075415A1

公开(公告)日：2005-08-18

申请号：PCT/CZ2005/000010

申请日：2005-02-03

Applicant: ZENTIVA, A.S. ,  HAJICEK, Josef ,  SLAVIKOVA, Marketa

Inventor： HAJICEK, Josef ,  SLAVIKOVA, Marketa

IPC: C07C303/40

CPC classification number: C07C311/46 ,  C07B2200/07 ,  C07C303/38 ,  Y02P20/55 ,  C07C311/37

Abstract: A method of preparation of (R)-(-)-5-(2-aminopropyl)-2-methoxybenzenesulfonamide of formula I and its use for production tamsulosin. A protective group is introduced to N-[(1R)-2­(4-methoxyphenyl)-1-methylethyl]-N- [(1 R)-1-phenylethyl)]amine and the resulting amide of formula IX is chlorosulfonated and the resulting sulfochloride is converted to a sulfonamide of formula X, from which the compound of formula I is obtained by hydrogenation.

Abstract translation: 制备式I的（R） - （ - ） - 5-（2-氨基丙基）-2-甲氧基苯磺酰胺及其用于生产坦索罗辛的方法。 将保护基引入到N - [（1R）-2-（4-甲氧基苯基）-1-甲基乙基] -N- [（1R）-1-苯乙基）]胺中，得到式IX的酰胺氯磺化， 得到的磺酰氯转化成式X的磺酰胺，通过氢化获得式I化合物。

公开(公告)号：WO2005054211A1

公开(公告)日：2005-06-16

申请号：PCT/SK2004/000015

申请日：2004-11-30

Applicant: ZENTIVA, A.S. ,  LOPUCH, Jozef ,  PROKSA, Bohumil ,  VANDAK, Dusan

Inventor： LOPUCH, Jozef ,  PROKSA, Bohumil ,  VANDAK, Dusan

IPC: C07D243/24

CPC classification number: C07D243/24

Abstract: A new method of purification of Lorazepam is disclosed that consists in removing products of synthesis, decomposition products, water or other solvent that forms a solvate with Lorazepam, by crystallization or stirring in an organic solvent of the ether, ester or ketone type. Lorazepam prepared via this method can be utilized in the pharmaceutical industry for the manufacture of pharmaceuticals.

Abstract translation: 公开了一种纯化劳拉西泮的新方法，其包括除去合成产物，分解产物，水或其它与劳拉西泮形成溶剂化物的溶剂，通过在醚的有机溶剂中结晶或搅拌 ，酯或酮类型。 通过这种方法制备的劳拉西泮可用于制药工业中用于制造药物。

公开(公告)号：WO2004046080A1

公开(公告)日：2004-06-03

申请号：PCT/SK2003/000022

申请日：2003-11-11

Applicant: ZENTIVA, a.s. ,  VEVERKA, Miroslav ,  BOHÁC, Andrej ,  ALMÁSSY, Ambroz ,  ADDOVÁ, Gabriela ,  VARGA, Ivan

Inventor： VEVERKA, Miroslav ,  BOHÁC, Andrej ,  ALMÁSSY, Ambroz ,  ADDOVÁ, Gabriela ,  VARGA, Ivan

IPC: C07C67/475

CPC classification number: C07C67/27 ,  C07C2601/02 ,  C07C69/612 ,  C07C69/616 ,  C07C69/736 ,  C07C69/65

Abstract: The invention relates to a new preparation method of derivatives of substituted 2-­arylaikanoic acids. The compounds are used for the preparation of histaminically active compounds and antiphlogistics. The compounds are prepared by reaction of suitably substituted a-halogen acetophenones with orthoformates with catalysis by mineral and Lewis acids.

Abstract translation: 本发明涉及取代的2-芳基酸的衍生物的新的制备方法。 该化合物用于制备组胺活性化合物和消炎药。 通过适当取代的α-卤代苯乙酮与原甲酸酯与矿物和路易斯酸的催化反应来制备化合物。