公开(公告)号：EP1161236A1

公开(公告)日：2001-12-12

申请号：EP00907111.9

申请日：2000-02-02

申请人： Merck & Co., Inc.

发明人： TILLYER, Richard, D. ,  REIDER, Paul, J. ,  GRABOWSKI, Edward, J., J. ,  XU, Feng ,  VEGA, Jose, M.

IPC分类号： A61K31/22 ,  A61P3/06 ,  A61K9/28

CPC分类号： A61K9/2833

摘要： The instant invention provides methods and pharmaceutical compositions for inhibiting HMG-CoA reductase, as well as for treating and/or reducing the risk for diseases and conditions affected by inhibition of HMG-CoA reductase, comprising orally administering a therapeutically effective amount of a compound selected from a dihydroxy open acid statin and a pharmaceutically acceptable salt or ester thereof in a delayed-release pharmaceutical dosage form to a patient in need of such treatment wherein substantial release of the compound from the dosage form is delayed until after passage of the dosage form through the stomach.

公开(公告)号：EP1071685A1

公开(公告)日：2001-01-31

申请号：EP99916629.1

申请日：1999-04-12

申请人： MERCK & CO., INC.

发明人： PYE, Philip, J. ,  REIDER, Paul, J. ,  ROSSEN, Kai ,  VOLANTE, Ralph, P.

IPC分类号： C07D477/14

CPC分类号： C07D477/04 ,  C07D205/08

摘要： An efficient method for the synthesis of a compound of formula (2) is disclosed which comprises reacting a 4-acyl-2-azetidinone with a titanium, zirconium or hafnium enolate of a 1-hydroxy-2-butanone derivative.

公开(公告)号：EP0823904A1

公开(公告)日：1998-02-18

申请号：EP96911786.0

申请日：1996-04-15

申请人： MERCK & CO., INC.

发明人： ASKIN, David ,  MALIGRES, Peter, E. ,  REIDER, Paul, J. ,  ROSSEN, Kai ,  SAGER, Jess ,  UPADHYAY, Veena ,  VOLANTE, Ralph, P. ,  WELLS, Kenneth, M.

IPC分类号： C07D471

CPC分类号： C07D471/10 ,  Y02P20/55

摘要： The present invention is directed to a novel process for the preparation of a spiroindoline sulfonamides of formula (I), wherein L is hydrogen or an amino protecting group. These compounds are useful in the preparation of certain spiro compounds which have the ability to stimulate the release of natural or endogeneous growth hormone. The spiro compounds may be used to treat conditions which require the stimulation of growth hormone production or secretion such as in humans with a deficiency of natural growth hormone or in animals used for food or wool production where the stimulation of growth hormone will result in a larger, more productive animal.

公开(公告)号：EP1007511B1

公开(公告)日：2003-07-02

申请号：EP98943349.5

申请日：1998-08-24

申请人： MERCK & CO., INC.

发明人： CHOI, Woo-Baeg ,  LEE, Jaemoon ,  LYNCH, Joseph, E. ,  REIDER, Paul, J. ,  VOLANTE, Ralph, P.

IPC分类号： C07D205/08 ,  C07F7/18

CPC分类号： C07D205/08 ,  C07F7/186 ,  Y02P20/55

摘要： The instant invention relates to a compound of formula (I) wherein Ra and P are: (a) hydrogen, (b) methyl, or (c) a hydroxy protecting group and an efficient process for its synthesis.

公开(公告)号：EP0748319B1

公开(公告)日：2001-12-12

申请号：EP95911105.5

申请日：1995-02-27

申请人： Merck & Co., Inc.

发明人： ASKIN, David ,  ENG, Kan, K. ,  MALIGRES, Peter, E. ,  REIDER, Paul, J. ,  ROSSEN, Kai ,  VOLANTE, Ralph, P. ,  UPADHYAY, Veena

IPC分类号： C07D413/06 ,  C07D263/52 ,  C07D413/04

CPC分类号： C07D263/52 ,  C07D413/06

摘要： A process for synthesizing the epoxide of formula (I) consists of, at a minimum, formation of a halohydrin form the allyl acetonide reactant, followed by base-induced cyclization, the epoxide product (I) being useful as an intermediate for the synthesis of inhibitors of renin or HIV protease or other proteases.

公开(公告)号：EP1115741A2

公开(公告)日：2001-07-18

申请号：EP99948329.0

申请日：1999-09-20

申请人： MERCK & CO., INC.

发明人： HUFFMAN, Mark, A. ,  REIDER, Paul, J. ,  LEBLOND, Carl ,  SUN, Yongkui

IPC分类号： C07K5/02

CPC分类号： C07D207/16 ,  A61K38/00 ,  C07K5/0222

摘要： The invention relates to an improved stereoselective heterogenous catalytic reductive amination between ethyl 2-oxo-4-phenylbutyrate and alanylproline using hydrogen, a catalyst and one or more additives to produce the ACE inhibitor, enalapril.

公开(公告)号：EP0912517B1

公开(公告)日：2000-10-25

申请号：EP97922629.7

申请日：1997-05-05

申请人： MERCK & CO., INC.

发明人： CHOI, Woo-Baeg ,  CHURCHILL, Hywyn, R., D. ,  LYNCH, Joseph, E. ,  REIDER, Paul, J. ,  VOLANTE, Ralph, P.

IPC分类号： C07D213/30 ,  C07D213/54 ,  A61K31/44

CPC分类号： C07D213/30 ,  C07D213/38

摘要： A process for the preparation of Phosphodiesterase IV inhibitors of structural formula VIII, wherein R' is (substituted) phenyl, is described. The process consists of eight chemical steps involving five isolations to prepare the title compound from readily available isovanillin in 35 % overall yield (Scheme 1). The process is highlighted by: a) a highly diastereoselective Michael addition of phenyllithium using (1R, 2S) cis-aminoindanol as a chiral auxiliary, b) highly crystalline intermediates providing for efficient purifications, c) crystallization of the final compound as its CSA salt for excellent enantiomeric purity.

公开(公告)号：EP1017666B1

公开(公告)日：2003-11-05

申请号：EP98942339.7

申请日：1998-09-01

申请人： MERCK & CO., INC.

发明人： CHEN, Cheng, Yi ,  REIDER, Paul, J. ,  GRABOWSKI, Edward, J., J. ,  TAN, Lushi ,  TILLYER, Richard, D.

IPC分类号： C07C209/88 ,  C07C211/46 ,  C07C211/52 ,  C07C213/10 ,  C07B57/00

CPC分类号： C07C213/10 ,  C07B2200/07 ,  C07C2601/02 ,  C07C215/70

摘要： A process for enhancing the purity of 2R-[1-hydroxy- 1-trifluoromethyl- 3-cyclopropylpropyn-2-yl] -4-chloroaniline comprising the formation of an acid addition salt which is capable of rejecting the racemate in the selected organic solvent.

摘要翻译： 一种用于增强2R-的纯度工艺[1-羟基-1-三氟甲基-3- cyclopropylpropyn -2-基] -4-氯苯胺，包括酸加成盐的所有其能够在所选择的有机溶剂中拒绝所述外消旋物的形成 ，

公开(公告)号：EP1324972A1

公开(公告)日：2003-07-09

申请号：EP01968480.2

申请日：2001-09-05

申请人： Merck & Co., Inc.

发明人： TILLYER, Richard, D. ,  REIDER, Paul, J. ,  GRABAOWSKI, Edward, J. J. ,  XU, Feng ,  WENSLOW, Robert, M. ,  VEGA, Jose, M. ,  VARSOLONA, Richard, J.

IPC分类号： C07C69/30 ,  C07C67/28 ,  A61K9/28 ,  A61K31/22

CPC分类号： A61K31/366 ,  A61K9/0004 ,  A61K31/22 ,  C07C69/30 ,  C07C2602/28 ,  C07D309/30

摘要： The instant invention provides methods and pharmaceutical compositions for inhibiting HMG-CoA reductase, as well as for treating and/or reducing the risk for diseases and conditions affected by inhibition of HMG-CoA reductase, comprising orally administering a therapeutically effective amount of a crystalline hydrated form of the calcium salt of dihydroxy open acid simvastatin to a patient in need of such treatment. Methods for making the calcium salt of dihydroxy open acid simvastatin are also provided.

公开(公告)号：EP1163203A1

公开(公告)日：2001-12-19

申请号：EP00904644.2

申请日：2000-02-02

申请人： Merck & Co., Inc.

发明人： TILLYER, Richard, D. ,  REIDER, Paul, J. ,  GRABOWSKI, Edward, J., J. ,  XU, Feng

IPC分类号： C07C69/30 ,  C07C67/28 ,  A61K31/22 ,  A61P3/06

CPC分类号： C07D309/30 ,  A61K9/0004 ,  A61K31/22 ,  C07C69/30 ,  C07C2602/28

摘要： The instant invention provides methods and pharmaceutical compositions for inhibiting HMG-CoA reductase, as well as for treating and/or reducing the risk for diseases and conditions affected by inhibition of HMG-CoA reductase, comprising orally administering a therapeutically effective amount of a crystalline hydrated form of the calcium salt of dihydroxy open acid simvastatin to a patient in need of such treatment. Methods for making the calcium salt of dihydroxy open acid simvastatin are also provided.

摘要翻译： 本发明提供二羟基开酸辛伐他汀的钙盐的结晶水合物，其可用于抑制HMG-CoA还原酶，以及用于治疗和/或降低受HMG-CoA还原酶抑制影响的疾病和病症的风险。 描述了制备二羟基开酸辛伐他汀钙盐的特定结晶水合物的方法。 还提供了活性剂的常规制剂，包括快速释放，时间释放和延迟释放制剂。