公开(公告)号：EP1912642A2

公开(公告)日：2008-04-23

申请号：EP06788290.2

申请日：2006-07-24

申请人： Merck & Co., Inc. ,  BANYU PHARMACEUTICAL CO., LTD.

发明人： FERLITA, Russell, R. ,  HAGA, Yuji ,  ISHIKAWA, Makoto ,  KAMEI, Keisuke ,  KATO, Shinji ,  KOJIMA, Hisaki ,  MOMENT, Aaron ,  NONOYAMA, Nobuaki ,  SATAKE, Nobuya ,  SHIGEMORI, Kazuki ,  WADA, Toshihiro ,  WANG, Yaling ,  WEISSMAN, Steven, A. ,  WENSLOW, Robert, M.

IPC分类号： A61K31/4355 ,  C07D491/048

CPC分类号： C07D491/10

摘要： The present invention relates to a process for producing crystalline trans-N-[l-(2-fluorophenyl)- S-pyrazoly]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide and novel salts, hydrates and polymorphs thereof.

公开(公告)号：EP1442038A2

公开(公告)日：2004-08-04

申请号：EP02768879.5

申请日：2002-09-20

申请人： Merck & Co., Inc.

发明人： BRANDS, Karel, M., J. ,  CVETOVICH, Raymond ,  CROCKER, Louis, S. ,  WARD, Michael, D. ,  MAHAJAN, Amar, J. ,  WENSLOW, Robert, M. ,  WILLIAMS, John, M. ,  SIDLER, Daniel, R. ,  FISHER, Elizabeth, S. ,  JOBSON, Ronald ,  ORELLA, Charles

IPC分类号： C07D477/20

CPC分类号： C07D477/20

摘要： A process for preparing a crystalline, carbapenem monosodium salt of formula IIa, characterized by the steps a) adding about 10 to 30 % of an organic solvent to an aqueous solution of the carbapenem, b) cooling the resulting solution to less than -5 °C, c) adjusting the pH using a solution containing an acid in an organic solvent to give the appropriate pH for crystallization, and d) crystallizing the compound by adding methanol, and a C2-5 alcohol at between -5 and -25 °C.

公开(公告)号：EP1667524A2

公开(公告)日：2006-06-14

申请号：EP04784324.8

申请日：2004-09-17

申请人： Merck & Co., Inc.

发明人： CHEN, Alex, M. ,  WENSLOW, Robert, M.

IPC分类号： A01N43/58 ,  A01N43/60 ,  A61K31/495 ,  A61K31/50

CPC分类号： C07D487/04

摘要： The present invention relates to a novel crystalline anhydrate polymorph of the dihydrogenphosphate salt of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-a mine as well as a process for their preparation, pharmaceutical compositions containing this novel form, and methods of use of the novel form and pharmaceutical compositions for the treatment of diabetes, obesity, and high blood pressure.

公开(公告)号：EP1662876A2

公开(公告)日：2006-06-07

申请号：EP04782460.2

申请日：2004-08-27

申请人： Merck & Co., Inc.

发明人： WENSLOW, Robert, M. ,  ARMSTRONG, Joseph, D., III ,  CHEN, Alex, M. ,  CYPES, Stephen ,  FERLITA, Russell, R. ,  HANSEN, Karl ,  LINDEMANN, Christopher, M. ,  SPARTALIS, Evangelia

IPC分类号： A01N43/58 ,  A01N43/60 ,  A61K31/495 ,  A61K31/50

CPC分类号： C07D487/04

摘要： The present invention relates to crystalline anhydrate polymorphs of the dihydrogenphosphate salt of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-α]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine as well as a process for their preparation, pharmaceutical compositions containing these novel forms, and methods of use of the novel forms and pharmaceutical compositions for the treatment of diabetes, obesity, and high blood pressure. The invention also concerns novel crystalline solvates of the dihydrogenphosphate salt of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-α]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine as well as a crystalline desolvated polymorph and their use for the preparation of the anhydrate polymorphs of the present invention.

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：EP1909776A2

公开(公告)日：2008-04-16

申请号：EP06836090.8

申请日：2006-07-21

申请人： Merck & Co., Inc.

发明人： ELLISON, Martha, E. ,  PERESYPKIN, Andrey, V. ,  WENSLOW, Robert, M.

IPC分类号： A61K31/10

CPC分类号： C07D487/04

摘要： The dodecylsulfate salt of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6- dihydro[l,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-l-(2,4,5-trifluorophenyl)butan-2-amine is a potent inhibitor of dipeptidyl peptidase-IV and is useful for the treatment of Type 2 diabetes. The invention also relates to a crystalline anhydrate of the dodecylsulfate salt as well as a process for its preparation, pharmaceutical compositions containing this novel form and methods of use for the treatment of Type 2 diabetes, hyperglycemia, insulin resistance, and obesity.

公开(公告)号：EP1796671A1

公开(公告)日：2007-06-20

申请号：EP05796471.0

申请日：2005-09-09

申请人： Merck & Co., Inc.

发明人： FERLITA, Russell, R. ,  WENSLOW, Robert, M.

IPC分类号： A61K31/4985 ,  C07D487/04

CPC分类号： C07D487/04

摘要： The present invention relates to a novel amorphous form of the dihydrogenphosphate salt of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-a mine as well as a process for its preparation, pharmaceutical compositions containing this novel form, and methods of use of the novel form and pharmaceutical compositions for the treatment of diabetes, obesity, and high blood pressure.

公开(公告)号：EP1765771A2

公开(公告)日：2007-03-28

申请号：EP05768999.4

申请日：2005-07-01

申请人： Merck & Co., Inc.

发明人： CAMPOS, Kevin, R. ,  KLAPARS, Artis ,  MCWILLIAMS, J. Christopher ,  SHULTZ, C. Scott ,  WALLACE, Debra, J. ,  CHEN, Alex, M. ,  FREY, Lisa, F. ,  PERESYPKIN, Andrey, V. ,  WANG, Yaling ,  WENSLOW, Robert, M. ,  CHEN, Cheng-Yi

IPC分类号： C07C233/00 ,  C07D211/72

CPC分类号： C07C231/18 ,  C07C253/14 ,  C07C309/73 ,  C07D213/64 ,  C07C255/56

摘要： The present invention is directed to a practical process for the preparation of an enamide (II) by palladium catalyzed coupling of a primary amide (IV) with a compound of structural formula (III), as shown below: As well as to crystalline forms of a compound produced by this process, in particular, an anhydrous crystal form, Form B, and crystalline solvates falling into three patterns, Type 1, Type 2, and Type 3, and crystalline intermediate compounds produced in the process. Still further, the present invention relates to the stereoselective reduction of the tetrasubstituted enamide (II) to the corresponding amide (I).