公开(公告)号：EP0938483B1

公开(公告)日：2003-02-26

申请号：EP97936296.9

申请日：1997-08-06

申请人： SCHERING CORPORATION

发明人： LOWE, Derek, B. ,  CHANG, Wei, K. ,  KOZLOWSKI, Joseph, A. ,  BERGER, Joel, G. ,  McQUADE, Robert ,  BARNETT, Allen ,  SHERLOCK, Margaret ,  TOM, Wing ,  DUGAR, Sundeep ,  CHEN, Lian-Yong ,  CLADER, John, W. ,  CHACKALAMANNIL, Samuel ,  WANG, Yuguang ,  McCOMBIE, Stuart, W. ,  TAGAT, Jayaram, R. ,  VICE, Susan, F. ,  VACCARO, Wayne, D. ,  GREEN, Michael, J. ,  BROWNE, Margaret, E. ,  BOYLE, Craig, D. ,  JOSIEN, Hubert, B. ,  ASBEROM, Theodros

IPC分类号： C07D405/00 ,  A61K31/00

CPC分类号： C07D405/14 ,  C07C2601/14 ,  C07D211/24 ,  C07D211/32 ,  C07D239/34 ,  C07D257/04 ,  C07D295/03 ,  C07D295/088 ,  C07D295/092 ,  C07D295/096 ,  C07D295/112 ,  C07D295/116 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/145 ,  C07D295/15 ,  C07D405/12 ,  C07D409/14

摘要： Di-N-substituted piperazine or 1,4 di-substituted piperidine compounds in accordance with formula I (including all isomers, salts, esters, and solvates) wherein R, R?1, R2, R3, R4, R21, R27, R28¿, X, Y and Z as defined herein are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease. Pharmaceutical compositions and methods of preparation are also disclosed. Also disclosed are synergistic combinations of compounds of the above formula with acetylcholinesterase inhibitors.

摘要翻译： 根据式I的二-N-取代哌嗪或1,4-二取代哌啶化合物（包括所有异构体，盐，酯和溶剂合物），其中R，R 1，R 2，R 3，R 4，R 21，R 27，R 28，X ，Y和Z如本文所定义的是可用于治疗认知障碍如阿尔茨海默氏病的毒蕈碱拮抗剂。 还公开了药物组合物和制备方法。 还公开了上式化合物与乙酰胆碱酯酶抑制剂的协同组合。

公开(公告)号：EP0869942B1

公开(公告)日：2002-02-13

申请号：EP95943048.9

申请日：1995-12-18

申请人： SCHERING CORPORATION

发明人： VACCARO, Wayne, D. ,  BURNETT, Duane, A. ,  CLADER, John, W.

IPC分类号： C07D205/08 ,  C07D205/12 ,  C07D491/08 ,  C07D491/10 ,  C07D413/10 ,  C07D403/12 ,  C07D403/10 ,  A61K31/395

CPC分类号： C07D231/12 ,  C07D205/08 ,  C07D205/12 ,  C07D233/56 ,  C07D249/08 ,  C07D403/12 ,  C07D413/10 ,  C07D491/08 ,  C07D491/10

摘要： 4-[(Heterocycloalkyl or heteroaromatic)-substituted phenyl]-2-azetidinone hypocholesterolemic agents of formula (I) or a pharmaceutically acceptable salt thereof, wherein: A is optionally substituted heterocycloalkyl, optionally substituted heteroaryl, optionally substituted benzofused heterocycloalkyl, or optionally substituted benzofused heteroaryl; Ar1 is optionally substituted aryl; Ar2 is optionally substituted aryl; Q is a bond or, with the 3-position ring carbon of the azetidinone, forms the spiro group (a); and R1 is selected from the group consisting of -(CH¿2?)q-, wherein q is 2-6, provided that when Q is a spiro ring, q can also be 0 or 1; -(CH2)e-G-(CH2)r-, wherein G is -O-, -C(O)-, phenylene, -NR?8¿- or -S(O)¿0-2?-, e is 0-5 and r is 0-5, provided that the sum of e and r is 1-6; alkenylene; and -(CH2)f-V-(CH2)g-, wherein V is cycloalkylene, f is 1-5 and g is 0-5, provided that the sum of f and g is 1-6; R?5¿ is (b), (c), (d), (e), (f), (g) or (h); R?6 and R7¿ are -CH¿2?-, -CH(alkyl)-, -C(dialkyl), -CH=CH- or -C(alkyl)=CH-; or R?5¿ together with an adjacent R?6, or R5¿ together with an adjacent R7, form a -CH=CH- or a -CH=C(alkyl)- group; a and b are independently 0-3, provided both are not zero; and when Q is a bond, R1 also can be: (i), (j) or (k); M is -O-, -S-, -S(O)- or -S(O)¿2?-; X, Y and Z are -CH2-, -CH(alkyl)- or -C(dialkyl); R?10 and R12 -OR14¿, -O(CO)R14, -O(CO)OR16 or -O(CO)NR?14R15; R11 and R13¿ are H, alkyl or aryl; or R?10 and R11¿ together are =O, or R?12 and R13¿ together are =O; d is 1-3; h is 0-4; s is 0 or 1; t is 0 or 1; m, n and p are independently 0-4; provided that at least one of s and t is 1, and the sum of m, n, p, s and t is 1-6; provided that when p is 0 and t is 1, the sum of m, s and n is 1-5; and provided that when p is 0 and s is 1, the sum of m, t and n is 1-5; v is 0 or 1; j and k are independently 1-5, provided that the sum of j, k and v is 1-5; R8 is H, alkyl, arylalkyl, -C(O)R14 or -COOR14; R9 is H, alkyl, alkoxy, -COOH, NO¿2?, -NR?14R15¿, OH or halogeno; R?14 and R15¿ are H, alkyl, aryl and arylalkyl; R16 is alkyl or optionally substituted aryl; and R19 is H, OH or alkoxy are disclosed, as well as a method of lowering serum cholesterol by administering said compounds, pharmaceutical compositions containing them, and the combination of a substituted azetidinone and a cholesterol biosynthesis inhibitor for the treatment and prevention of atherosclerosis.

公开(公告)号：EP1159275A2

公开(公告)日：2001-12-05

申请号：EP00917775.9

申请日：2000-03-06

申请人： SCHERING CORPORATION

发明人： VACCARO, Wayne, D. ,  PIWINSKI, John, J. ,  TOM, Wing, C. ,  SOLOMON, Daniel, M. ,  ASLANIAN, Robert, G.

IPC分类号： C07D403/06 ,  A61K31/50 ,  A61P43/00 ,  C07D403/12 ,  C07D233/54 ,  C07D401/12 ,  C07D401/14 ,  C07D403/14

CPC分类号： C07D233/64 ,  C07D401/12 ,  C07D401/14 ,  C07D403/06 ,  C07D403/12 ,  C07D403/14

摘要： This invention discloses a compound having general formula depicted in Formula (I), wherein G is a spacer moiety selected from the group consisting of C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C1-C7 alkyl-NHCO-, and -SO2-, T is a six-membered ring or a seven-membered ring containing two ring nitrogens and belonging to formula (a), with said T ring being c onnected to said G moiety at either a ring carbon atom of ring T or a ring nitrogen atom of ring T: wherein n is 1 or 2. These compounds have excellent histamine-H3 receptor antagonist activity.

公开(公告)号：EP0938483A2

公开(公告)日：1999-09-01

申请号：EP97936296.0

申请日：1997-08-06

申请人： SCHERING CORPORATION

发明人： LOWE, Derek, B. ,  CHANG, Wei, K. ,  KOZLOWSKI, Joseph, A. ,  BERGER, Joel, G. ,  McQUADE, Robert ,  BARNETT, Allen ,  SHERLOCK, Margaret ,  TOM, Wing ,  DUGAR, Sundeep ,  CHEN, Lian-Yong ,  CLADER, John, W. ,  CHACKALAMANNIL, Samuel ,  WANG, Yuguang ,  McCOMBIE, Stuart, W. ,  TAGAT, Jayaram, R. ,  VICE, Susan, F. ,  VACCARO, Wayne, D. ,  GREEN, Michael, J. ,  BROWNE, Margaret, E. ,  BOYLE, Craig, D. ,  JOSIEN, Hubert, B. ,  ASBEROM, Theodros

IPC分类号： C07D211 ,  A61K31 ,  A61K45 ,  A61P25 ,  C07D239 ,  C07D257 ,  C07D295 ,  C07D401 ,  C07D405 ,  C07D409 ,  C07D413

CPC分类号： C07D405/14 ,  C07C2601/14 ,  C07D211/24 ,  C07D211/32 ,  C07D239/34 ,  C07D257/04 ,  C07D295/03 ,  C07D295/088 ,  C07D295/092 ,  C07D295/096 ,  C07D295/112 ,  C07D295/116 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/145 ,  C07D295/15 ,  C07D405/12 ,  C07D409/14

摘要： Di-N-substituted piperazine or 1,4 di-substituted piperidine compounds in accordance with formula I (including all isomers, salts, esters, and solvates) wherein R, R?1, R2, R3, R4, R21, R27, R28¿, X, Y and Z as defined herein are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease. Pharmaceutical compositions and methods of preparation are also disclosed. Also disclosed are synergistic combinations of compounds of the above formula with acetylcholinesterase inhibitors.

公开(公告)号：EP0877750A1

公开(公告)日：1998-11-18

申请号：EP96937702.0

申请日：1996-10-29

申请人： SCHERING CORPORATION

发明人： YUMIBE, Nathan, P. ,  ALTON, Kevin, B. ,  VAN HEEK, Margaret ,  DAVIS, Harry, R. ,  VACCARO, Wayne, D.

IPC分类号： C07H15 ,  A61K31 ,  A61K45 ,  A61P3 ,  A61P9 ,  C07H3 ,  C07H17

CPC分类号： C07H15/26

摘要： Hypocholesterolemic sugar-substituted 2-azetidinones are dislcosed, as well as a method of lowering cholesterol by administering said compounds, pharmaceutical compositions containing them, and the combination of a sugar-substituted 2-azetidinone cholesterol-lowering agent and a cholesterol biosynthesis inhibitor for the treatment and prevention of atherosclerosis.

公开(公告)号：EP0877750B1

公开(公告)日：2002-06-19

申请号：EP96937702.7

申请日：1996-10-29

申请人： SCHERING CORPORATION

发明人： YUMIBE, Nathan, P. ,  ALTON, Kevin, B. ,  VAN HEEK, Margaret ,  DAVIS, Harry, R. ,  VACCARO, Wayne, D.

IPC分类号： C07H3/04 ,  C07H17/02 ,  A61K31/70

CPC分类号： C07H15/26

摘要： Hypocholesterolemic sugar-substituted 2-azetidinones are dislcosed, as well as a method of lowering cholesterol by administering said compounds, pharmaceutical compositions containing them, and the combination of a sugar-substituted 2-azetidinone cholesterol-lowering agent and a cholesterol biosynthesis inhibitor for the treatment and prevention of atherosclerosis.

公开(公告)号：EP1028956A1

公开(公告)日：2000-08-23

申请号：EP98956443.0

申请日：1998-11-05

申请人： SCHERING CORPORATION

发明人： VACCARO, Wayne, D. ,  WOLIN, Ronald, L. ,  SOLOMON, Daniel, M. ,  ASLANIAN, Robert, G. ,  PIWINSKI, John, J. ,  ROSENBLUM, Stuart, B.

IPC分类号： C07D401/06 ,  C07D403/06 ,  A61K31/445 ,  A61K31/415

CPC分类号： C07D401/06 ,  A61K31/445 ,  A61K31/495 ,  C07D403/06 ,  A61K31/415 ,  A61K2300/00

摘要： Disclosed are compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof. Also disclosed are pharmaceutical compositions comprising a pharmaceutically acceptable carrier and an effective amount of a Compound of Formula (I). Further disclosed is a method of treating allergy (for example asthma), inflammation, hypotension, raised intraocular pressure (such as glaucoma) i.e., a method of lowering intraocular pressure, sleeping disorders, states of hyper and hypo motility and acidic secretion of the gastrointestinal tract, hypo and hyperactivity of the central nervous system (for example, agitation and depression) and other CNS disorders (such as Alzheimer's, Schizophrenia, obesity and migraine) comprising administering an effective amount of a compound of Formula (I) to a patient in need of such treatment. Also disclosed are methods for treatment of upper airway allergic responses comprising administering a compound, or salt or solvate thereof, of Formula (I) in combination or admixture with a histamine H1 receptor antagonist.

公开(公告)号：EP0869942A1

公开(公告)日：1998-10-14

申请号：EP95943048.0

申请日：1995-12-18

申请人： SCHERING CORPORATION

发明人： VACCARO, Wayne, D. ,  BURNETT, Duane, A. ,  CLADER, John, W.

IPC分类号： A61K31 ,  A61P3 ,  A61P9 ,  C07D205 ,  C07D401 ,  C07D403 ,  C07D413 ,  C07D491 ,  C07D521

CPC分类号： C07D231/12 ,  C07D205/08 ,  C07D205/12 ,  C07D233/56 ,  C07D249/08 ,  C07D403/12 ,  C07D413/10 ,  C07D491/08 ,  C07D491/10

摘要： 4-[(Heterocycloalkyl or heteroaromatic)-substituted phenyl]-2-azetidinone hypocholesterolemic agents of formula (I) or a pharmaceutically acceptable salt thereof, wherein: A is optionally substituted heterocycloalkyl, optionally substituted heteroaryl, optionally substituted benzofused heterocycloalkyl, or optionally substituted benzofused heteroaryl; Ar1 is optionally substituted aryl; Ar2 is optionally substituted aryl; Q is a bond or, with the 3-position ring carbon of the azetidinone, forms the spiro group (a); and R1 is selected from the group consisting of -(CH¿2?)q-, wherein q is 2-6, provided that when Q is a spiro ring, q can also be 0 or 1; -(CH2)e-G-(CH2)r-, wherein G is -O-, -C(O)-, phenylene, -NR?8¿- or -S(O)¿0-2?-, e is 0-5 and r is 0-5, provided that the sum of e and r is 1-6; alkenylene; and -(CH2)f-V-(CH2)g-, wherein V is cycloalkylene, f is 1-5 and g is 0-5, provided that the sum of f and g is 1-6; R?5¿ is (b), (c), (d), (e), (f), (g) or (h); R?6 and R7¿ are -CH¿2?-, -CH(alkyl)-, -C(dialkyl), -CH=CH- or -C(alkyl)=CH-; or R?5¿ together with an adjacent R?6, or R5¿ together with an adjacent R7, form a -CH=CH- or a -CH=C(alkyl)- group; a and b are independently 0-3, provided both are not zero; and when Q is a bond, R1 also can be: (i), (j) or (k); M is -O-, -S-, -S(O)- or -S(O)¿2?-; X, Y and Z are -CH2-, -CH(alkyl)- or -C(dialkyl); R?10 and R12 -OR14¿, -O(CO)R14, -O(CO)OR16 or -O(CO)NR?14R15; R11 and R13¿ are H, alkyl or aryl; or R?10 and R11¿ together are =O, or R?12 and R13¿ together are =O; d is 1-3; h is 0-4; s is 0 or 1; t is 0 or 1; m, n and p are independently 0-4; provided that at least one of s and t is 1, and the sum of m, n, p, s and t is 1-6; provided that when p is 0 and t is 1, the sum of m, s and n is 1-5; and provided that when p is 0 and s is 1, the sum of m, t and n is 1-5; v is 0 or 1; j and k are independently 1-5, provided that the sum of j, k and v is 1-5; R8 is H, alkyl, arylalkyl, -C(O)R14 or -COOR14; R9 is H, alkyl, alkoxy, -COOH, NO¿2?, -NR?14R15¿, OH or halogeno; R?14 and R15¿ are H, alkyl, aryl and arylalkyl; R16 is alkyl or optionally substituted aryl; and R19 is H, OH or alkoxy are disclosed, as well as a method of lowering serum cholesterol by administering said compounds, pharmaceutical compositions containing them, and the combination of a substituted azetidinone and a cholesterol biosynthesis inhibitor for the treatment and prevention of atherosclerosis.