公开(公告)号：USRE42461E1

公开(公告)日：2011-06-14

申请号：US12797341

申请日：1994-09-14

申请人： Stuart B. Rosenblum ,  Sundeep Dugar ,  Duane A. Burnett ,  John W. Clader ,  Brian A. McKittrick

发明人： Stuart B. Rosenblum ,  Sundeep Dugar ,  Duane A. Burnett ,  John W. Clader ,  Brian A. McKittrick

IPC分类号： C07D205/08 ,  A61P9/10 ,  A61P3/06 ,  A61K31/395

CPC分类号： C07D205/08 ,  A61K9/2018 ,  A61K9/4858 ,  A61K31/21 ,  A61K31/35 ,  A61K31/395 ,  A61K31/40 ,  A61K45/06 ,  Y02P20/55 ,  Y10S514/824 ,  A61K2300/00

摘要： Hydroxy-substituted azetidinone hypocholesterolemic agents of the formula or a pharmaceutically acceptable salt thereof, wherein: Ar1 and Ar2 are aryl or R4-substituted aryl; Ar3 is aryl or R5-substituted aryl; X, Y and Z are —CH2—, —CH(lower alkyl)— or —C(dilower alkyl)—; R and R2 are —OR6, —O(CO)R6, —O(CO)OR9 or —O(CO)NR6R7; R1 and R3 are H or lower alkyl; q is 0 or 1; r is 0 or 1; m, n and p are 0-4; provided that at least one of q and r is 1, and the sum of m, n, p, q and r is 1-6; and provided that when p is O and r is 1, the sum of m, q and n is 1-5; R4 is selected from lower alkyl, R5, —CF3, —CN, —NO2 and halogen R5 is selected from —OR6, —O(CO)R6, —O(CO)OR9, —O(CH2)1-5OR6, —O(CO)NR6R7, —NR6R7, —NR6(CO)R7, —NR6(CO)OR9, —NR6(CO)NR7R8, —NR6SO2R9, —COOR6, —CONR6R7, —COR6, —SO2NR6R7, S(O)0-2R9, —O(CH2)1-10—COOR6, —O(CH2)1-10CON6R7, —(lower alkylene)COOR6 and —CH═CH—COOR6; R6, R7 and R8 are H, lower alkyl or aryl-substituted Ic R9 is lower alkyl, aryl or aryl-substituted lower alkyl; are disclosed, as well as a method of lowering serum cholesterol by administering said compounds, alone or in combination with a cholesterol biosynthesis inhibitor, pharmaceutical compositions containing them; and a process for preparing them.

摘要翻译： 羟基取代的氮杂环丁酮低胆固醇血药剂或其药学上可接受的盐，其中：Ar 1和Ar 2是芳基或R 4取代的芳基; Ar 3是芳基或者R 5取代的芳基; X，Y和Z是-CH 2 - ， - CH（低级烷基） - 或-C（二卤代烷基） - 。 R和R 2为-OR 6，-O（CO）R 6，-O（CO）OR 9或-O（CO）NR 6 R 7; R1和R3是H或低级烷基; q为0或1; r为0或1; m，n和p为0-4; 条件是q和r中的至少一个为1，m，n，p，q和r的和为1-6; 并且条件是当p为O且r为1时，m，q和n的和为1-5; R4选自低级烷基，R5，-CF3，-CN，-NO2，卤素R5选自-OR6，-O（CO）R6，-O（CO）OR9，-O（CH2）1-5OR6， - O（CO）NR6R7，-NR6R7，-NR6（CO）R7，-NR6（CO）OR9，-NR6（CO）NR7R8，-NR6SO2R9，-COOR6，-CONR6R7，-COR6，-SO2NR6R7，S（O） -2R9，-O（CH2）1-10-COOR6，-O（CH2）1-10CON6R7， - （低级亚烷基）COOR6和-CH = CH-COOR6; R6，R7和R8是H，低级烷基或芳基取代的Ic R9是低级烷基，芳基或芳基取代的低级烷基; 以及通过单独或与胆固醇生物合成抑制剂组合含有它们的药物组合物来施用所述化合物来降低血清胆固醇的方法; 和一个准备它们的过程。

公开(公告)号：US5767115A

公开(公告)日：1998-06-16

申请号：US617751

申请日：1996-03-18

申请人： Stuart B. Rosenblum ,  Sundeep Dugar ,  Duane A. Burnett ,  John W. Clader ,  Brian A. McKittrick

发明人： Stuart B. Rosenblum ,  Sundeep Dugar ,  Duane A. Burnett ,  John W. Clader ,  Brian A. McKittrick

IPC分类号： A61K31/21 ,  A61K31/35 ,  A61K31/395 ,  A61K31/397 ,  A61K31/40 ,  A61P3/06 ,  A61P7/00 ,  A61P9/10 ,  C07D205/08

CPC分类号： C07D205/08 ,  Y02P20/55

摘要： Hydroxy-substituted azetidinone hypocholesterolemic agents of the formula ##STR1## or a pharmaceutically acceptable salt thereof, wherein: Ar.sup.1 and Ar.sup.2 are aryl or R.sup.4 -substituted aryl; Ar.sup.3 is aryl or R.sup.5 -substituted aryl; X, Y and Z are --CH.sub.2 --, --CH(lower alkyl)-- or --C(dilower alkyl)--; R and R.sup.2 are --OR.sup.6, --O(CO)R.sup.6, --O(CO)OR.sup.9 or --O(CO)NR.sup.6 R.sup.7 ; R.sup.1 and R.sup.3 are H or lower alkyl; q is 0 or 1; r is 0 or 1; m, n and p are 0-4; provided that at least one of q and r is 1, and the sum of m, n, p, q and r is 1-6; and provided that when p is O and r is 1, the sum of m, q and n is 1-5; R.sup.4 is selected from lower alkyl, R.sup.5, --CF.sub.3, --CN, --NO.sub.2 and halogen R.sup.5 is selected from --OR.sup.6, --O(CO)R.sup.6, --O(CO)OR.sup.9, --O(CH.sub.2).sub.1-5 OR.sup.6, --O(CO)NR.sup.6 R.sup.7, --NR.sub.6 R.sup.7, --NR.sup.6 (CO)R.sup.7, --NR.sup.6 (CO)OR.sup.9, --NR.sup.6 (CO)NR.sup.7 R.sup.8, --NR.sup.6 SO.sub.2 R.sup.9, --COOR.sup.6, --CONR.sup.6 R.sup.7, --COR.sup.6, --SO.sub.2 NR.sup.6 R.sup.7, S(O).sub.0-2 R.sup.9, --O(CH.sub.2).sub.1-10 --COOR.sup.6, --O(CH.sub.2).sub.1-10 CONR.sup.6 R.sup.7, --(lower alkylene)COOR.sup.6 and --CH.dbd.CH--COOR.sup.6 ; R.sup.6, R.sup.7 and R.sup.8 are H, lower alkyl, aryl or aryl-substituted Ic R.sup.9 is lower alkyl, aryl or aryl-substituted lower alkyl; are disclosed, as well as a method of lowering serum cholesterol by administering said compounds, alone or in combination with a cholesterol biosynthesis inhibitor, pharmaceutical compositions containing them; and a process for preparing them.

摘要翻译： 式（I）的羟基取代的氮杂环丁酮降胆固醇剂或其药学上可接受的盐，其中：Ar 1和Ar 2是芳基或R 4取代的芳基; Ar 3是芳基或者R 5取代的芳基; X，Y和Z是-CH 2 - ， - CH（低级烷基） - 或-C（二卤代烷基） - 。 R和R 2为-OR 6，-O（CO）R 6，-O（CO）OR 9或-O（CO）NR 6 R 7; R1和R3是H或低级烷基; q为0或1; r为0或1; m，n和p为0-4; 条件是q和r中的至少一个为1，m，n，p，q和r的和为1-6; 并且条件是当p为O且r为1时，m，q和n的和为1-5; R4选自低级烷基，R5，-CF3，-CN，-NO2，卤素R5选自-OR6，-O（CO）R6，-O（CO）OR9，-O（CH2）1-5OR6， - O（CO）NR6R7，-NR6R7，-NR6（CO）R7，-NR6（CO）OR9，-NR6（CO）NR7R8，-NR6SO2R9，-COOR6，-CONR6R7，-COR6，-SO2NR6R7，S（O） -2R9，-O（CH2）1-10-COOR6，-O（CH2）1-10CONR6R7， - （低级亚烷基）COOR6和-CH = CH-COOR6; R6，R7和R8是H，低级烷基，芳基或芳基取代的Ic R9是低级烷基，芳基或芳基取代的低级烷基; 以及通过单独或与胆固醇生物合成抑制剂组合含有它们的药物组合物来施用所述化合物来降低血清胆固醇的方法; 和一个准备它们的过程。

公开(公告)号：US5846966A

公开(公告)日：1998-12-08

申请号：US953825

申请日：1997-10-14

申请人： Stuart B. Rosenblum ,  Sundeep Dugar ,  Duane A. Burnett ,  John W. Clader ,  Brian A. McKittrick

发明人： Stuart B. Rosenblum ,  Sundeep Dugar ,  Duane A. Burnett ,  John W. Clader ,  Brian A. McKittrick

IPC分类号： A61K31/21 ,  A61K31/35 ,  A61K31/395 ,  A61K31/397 ,  A61K31/40 ,  A61P3/06 ,  A61P7/00 ,  A61P9/10 ,  C07D205/08

CPC分类号： A61K45/06 ,  A61K31/21 ,  A61K31/35 ,  A61K31/395 ,  A61K31/40 ,  A61K9/2018 ,  A61K9/4858 ,  Y10S514/824

摘要： Hydroxy-substituted azetidinone hypocholesterolemic agents of the formula ##STR1## or a pharmaceutically acceptable salt thereof, wherein: Ar.sup.1 and Ar.sup.2 are aryl or R.sup.4 -substituted aryl; Ar.sup.3 is aryl or R.sup.5 -substituted aryl; X, Y and Z are --CH.sub.2 --, --CH(lower alkyl)-- or --C(dilower alkyl)--; R and R.sup.2 are --OR.sup.6, --O(CO)R.sup.6, --O(CO)OR.sup.9 or --O(CO)NR.sup.6 R.sup.7 ; R.sup.1 and R.sup.3 are H or lower alkyl; q is 0 or 1; r is 0 or 1; m, n and p are 0-4; provided that at least one of q and r is 1, and the sum of m, n, p, q and r is 1-6; and provided that when p is 0 and r is 1, the sum of m, q and n is 1-5; R.sup.4 is selected from lower alkyl, R.sup.5, --CF.sub.3, --CN, --NO.sub.2 and halogen; R.sup.5 is selected from --OR.sup.6, --O(CO)R.sup.6, --O(CO)OR.sup.9, --O(CH.sub.2).sub.1-5 OR.sup.6, --O(CO)NR.sup.6 R.sup.7, --NR.sup.6 R.sup.7, --NR.sup.6 (CO)R.sup.7, --NR.sup.6 (CO)OR.sup.9, --NR.sup.6 (CO)NR.sup.7 R.sup.8, --NR.sup.6 SO.sub.2 R.sup.9, --COOR.sup.6, --CONR.sup.6 R.sup.7, --COR.sup.6, --SO.sub.2 NR.sup.6 R.sup.7, S(O).sub.0-2 R.sup.9, --O(CH.sub.2).sub.1-10 --COOR.sup.6, --O(CH.sub.2).sub.1-10 CONR.sup.6 R.sup.7, --(lower alkylene)COOR.sup.6 and --CH.dbd.CH--COOR.sup.6 ; R.sup.6, R.sup.7 and R.sup.8 are H, lower alkyl, aryl or aryl-substituted lower alkyl; R.sup.9 is lower alkyl, aryl or aryl-substituted lower alkyl; are disclosed, as well as a method of lowering serum cholesterol by administering said compounds, alone or in combination with a cholesterol biosynthesis inhibitor, pharmaceutical compositions containing them, and a process for preparing them.

摘要翻译： 式（I）的羟基取代的氮杂环丁酮降胆固醇剂或其药学上可接受的盐，其中：Ar 1和Ar 2是芳基或R 4取代的芳基; Ar 3是芳基或者R 5取代的芳基; X，Y和Z是-CH 2 - ， - CH（低级烷基） - 或-C（二卤代烷基） - 。 R和R 2为-OR 6，-O（CO）R 6，-O（CO）OR 9或-O（CO）NR 6 R 7; R1和R3是H或低级烷基; q为0或1; r为0或1; m，n和p为0-4; 条件是q和r中的至少一个是1，m，n，p，q和r的和是1-6; 并且当p为0且r为1时，m，q和n的和为1-5; R4选自低级烷基，R5，-CF3，-CN，-NO2和卤素; R5选自-OR6，-O（CO）R6，-O（CO）OR9，-O（CH2）1-5OR6，-O（CO）NR6R7，-NR6R7，-NR6（CO）R7，-NR6（ CO）OR 9，-NR 6（CO）NR 7 R 8，-NR 6 SO 2 R 9，-COOR 6，-CONR 6 R 7，-COR 6，-SO 2 NR 6 R 7，S（O）0-2R 9，-O（CH 2）1-10 -COOR 6，-O 1-10CONR6R7， - （低级亚烷基）COOR6和-CH = CH-COOR6; R6，R7和R8是H，低级烷基，芳基或芳基取代的低级烷基; R9是低级烷基，芳基或芳基取代的低级烷基; 以及通过单独或与胆固醇生物合成抑制剂组合使用所述化合物，含有它们的药物组合物及其制备方法来降低血清胆固醇的方法。

公开(公告)号：US5631365A

公开(公告)日：1997-05-20

申请号：US257593

申请日：1994-06-09

申请人： Stuart B. Rosenblum ,  Sundeep Dugar ,  Duane A. Burnett ,  John W. Clader ,  Brian A. McKittrick

发明人： Stuart B. Rosenblum ,  Sundeep Dugar ,  Duane A. Burnett ,  John W. Clader ,  Brian A. McKittrick

IPC分类号： A61K31/21 ,  A61K31/35 ,  A61K31/395 ,  A61K31/397 ,  A61K31/40 ,  A61P3/06 ,  A61P7/00 ,  A61P9/10 ,  C07D205/08

CPC分类号： C07D205/08 ,  Y02P20/55

摘要： A process for preparing compounds of the formula ##STR1## wherein R and R.sup.2 are independently --OH, --O(lower alkyl) or --0-benzyl and the remaining variables are as defined in the specification, comprising(a) treating with a strong base in an anhydrous organic solvent a lactone of the formula ##STR2## respectively, wherein Ar.sup.10 is Ar.sup.1 or a suitably protected hydroxy- or amino-substituted aryl, and R' and R.sup.2' are R and R.sup.2 as defined above or are suitably protected hydroxy groups;(b) reacting a product of step (a) with an imine of the formula ##STR3## wherein Ar.sup.20 and Ar.sup.30 are Ar.sup.2 or Ar.sup.3 or suitably protected hydroxy- or amino-substituted aryl;c) quenching the reaction with an acid; andd) removing protecting groups as necssary.

摘要翻译： 制备式IMA化合物的方法其中R和R 2独立地是-OH，-O（低级烷基）或-O-苄基，其余的变量如说明书中所定义，包括（a） 在无水有机溶剂中具有分子式为“IMAGE”的内酯的强碱，其中Ar10为Ar1或适当保护的羟基或氨基取代的芳基，R'和R2'为如上所定义的R和R 2，或者为 适当保护的羟基; （b）使步骤（a）的产物与下式的亚胺反应：其中Ar 20和Ar 30是Ar 2或Ar 3或适当保护的羟基或氨基取代的芳基; c）用酸淬灭反应; 和d）去除保护基团。

公开(公告)号：US5688787A

公开(公告)日：1997-11-18

申请号：US588785

申请日：1996-01-19

申请人： Duane A. Burnett ,  John W. Clader ,  Sundeep Dugar ,  Wayne Vaccaro

发明人： Duane A. Burnett ,  John W. Clader ,  Sundeep Dugar ,  Wayne Vaccaro

IPC分类号： C07D205/08 ,  C07D205/085 ,  C07D401/04 ,  C07D403/04 ,  C07D405/04 ,  C07D405/10 ,  C07D409/04 ,  C07F7/08 ,  C07F7/18 ,  A61K31/395 ,  C07D403/10

CPC分类号： C07D401/04 ,  C07D205/08 ,  C07D205/085 ,  C07D403/04 ,  C07D405/04 ,  C07D405/10 ,  C07D409/04 ,  C07F7/0812 ,  C07F7/186

摘要： Novel compounds of the formula ##STR1## wherein A is --CH.dbd.CH--B; --C.tbd.C--B; --(CH.sub.2).sub.p --X--B, and X is a bone, --NH-- or --S(O).sub.0-2 --; optionally substituted heteroaryl or benzofused heteroaryl; --C(O)--B; or ##STR2## D is B'--(CH.sub.2).sub.m C(O)--, B'--(CH.sub.2).sub.q --, B'--(CH.sub.2).sub.e --Z--(CH.sub.2).sub.r, wherein Z is --O--, --C(O)--, phenylene, --NR.sub.8 -- or --S(O).sub.0-2 --, B'--(alkenylene)--; B'--(alkadienylene)--; B'--(CH.sub.2).sub.t --Z--(alkenylene), B'--(CH.sub.2).sub.f --V--(CH.sub.2).sub.g --, wherein V is cycloalkylene, B'--(CH.sub.2).sub.t --V--(alkenylene) or B'--(alkenylene)--V--(CH.sub.2).sub.t --, B'--(CH.sub.2).sub.a --Z--(CH.sub.2).sub.b --V--(CH.sub.2).sub.d --, T--(CH.sub.2).sub.s --, wherein T is cycloalkyl; naphthylmethyl or optionally substituted heteroarylmethyl; B is optionally substituted phenyl; B' is naphthyl, optionally substituted heteroaryl or optionally substituted phenyl; R is hydrogen, fluoro, alkyl, alkenyl, alkynyl, or B--(CH.sub.2).sub.n --; R.sub.4 is optionally substituted phenyl, indanyl, benzofuranyl, tetrahydronaphthyl, pyridyl, pyrazinyl, pyrimidinyl or quinolyl; are disclosed, the method of using compounds of the formula II ##STR3## wherein R.sub.20 is optionally substituted phenyl, naphthyl, heteroaryl, or benzofused heteroaryl, R.sub.21, R.sub.22 and R.sub.23 are H or R.sub.20 ; E, F and G are independently a bond; cycloalkylene; alkylene; alkenylene; alkynylene; a substituted alkylene, alkenylene or alkynylene chain; an interrupted alkylene, alkenylene or alkynylene chain; or an interrupted alkylene, alkenylene or alkynylene chain substituted by one or more substituents; or one of R.sub.21 --E and R.sub.22 --F is selected from the group consisting of halogeno, OH, alkoxy, --OC(O)R.sub.5, --NR.sub.10 R.sub.11, --SH or --S(alkyl); R.sub.5 is alkyl, phenyl, R.sub.14 -phenyl, benzyl or R.sub.14 -benzyl; R.sub.10 and R.sub.11 are independently selected from H and lower alkyl, or a pharmaceutically acceptable salt thereof, in a pharmaceutically aceptable carrier as hypocholesterolemic agents is also disclosed.

公开(公告)号：USRE37721E1

公开(公告)日：2002-05-28

申请号：US09594996

申请日：2000-06-15

申请人： Stuart B. Rosenblum ,  Sundeep Dugar ,  Duane A. Burnett ,  John W. Clader ,  Brian A. McKittrick

发明人： Stuart B. Rosenblum ,  Sundeep Dugar ,  Duane A. Burnett ,  John W. Clader ,  Brian A. McKittrick

IPC分类号： C07D20508

CPC分类号： C07D205/08 ,  A61K9/2018 ,  A61K9/4858 ,  A61K31/21 ,  A61K31/35 ,  A61K31/395 ,  A61K31/40 ,  A61K45/06 ,  Y02P20/55 ,  Y10S514/824 ,  A61K2300/00

摘要： Hydroxy-substituted azetidinone hypocholesterolemic agents of the formula or a pharmaceutically acceptable salt thereof, wherein: Ar1 and Ar2 are aryl or R4-substituted aryl; Ar3 is aryl or R5-substituted aryl; X, Y and Z are —CH2—, —CH(lower alkyl)— or —C(dilower alkyl)—; R and R2 are —OR6, —O(CO)R6, —O(CO)OR9 or —O(CO)NR6R7; R1 and R3 are H or lower alkyl; q is 0 or 1; r is 0 or 1; m, n and p are 0-4; provided that at least one of q and r is 1, and the sum of m, n, p, q and r is 1-6; and provided that when p is O and r is 1, the sum of m, q and n is 1-5; R4 is selected from lower alkyl, R5, —CF3, —CN, —NO2 and halogen R5 is selected from —OR6, —O(CO)R6, —O(CO)OR9, —O(CH2)1-5OR6, —O(CO)NR6R7, —NR6R7, —NR6(CO)R7, —NR6(CO)OR9, —NR6(CO)NR7R8, —NR6SO2R9, —COOR6, —CONR6R7, —COR6, —SO2NR6R7, S(O)0-2R9, —O(CH2)1-10—COOR6, —O(CH2)1-10CONR6R7, —(lower alkylene)COOR6 and —CH═CH—COOR6; R6, R7 and R8 are H, lower alkyl or aryl-substituted Ic R9 is lower alkyl, aryl or aryl-substituted lower alkyl; are disclosed, as well as a method of lowering serum cholesterol by administering said compounds, alone or in combination with a cholesterol biosynthesis inhibitor, pharmaceutical compositions containing them; and a process for preparing them.

摘要翻译： 羟基取代的氮杂环丁酮低胆固醇血症药或其药学上可接受的盐，其中：Ar1和Ar2是芳基或R4取代的芳基; Ar3是芳基或R5-取代的芳基; X，Y和Z是-CH2-，-CH（ 低级烷基） - 或-C（二卤代烷基） - ; R和R 2为-OR 6，-O（CO）R 6，-O（CO）OR 9或-O（CO）NR 6 R 7; R 1和R 3为H或低级烷基; q为0或1; r为0或1; m，n和p为0-4; 条件是q和r中的至少一个为1，m，n，p，q和r的和为1-6; 并且条件是当p为O且r为1时，m，q和n的和为1-5; R 4选自低级烷基，R 5，-CF 3，-CN，-NO 2，卤素R 5选自-OR 6 ，-O（CO）R 6，-O（CO）OR 9，-O（CH 2）1-5 OR 6，-O（CO）NR 6 R 7，-NR 6 R 7，-NR 6（CO）R 7，-NR 6（CO）OR 9，-NR 6 （CO）NR7R8，-NR6SO2R9，-COOR6，-CONR6R7，-COR6，-SO2NR6R7，S（O）0-2R9，-O（CH2）1-10-COOR6，-O（CH2）1-10CONR6R7， - （ 低级亚烷基）COOR 6和-CH = CH-COOR 6; R6，R7和R8是H，低级烷基或芳基取代的IcR9是低级烷基，芳基或芳基取代的低级烷基;以及降低血清的方法 通过单独或与胆固醇生物合成抑制剂组合施用所述化合物，含有它们的药物组合物; 和一个准备它们的过程。

公开(公告)号：US5698548A

公开(公告)日：1997-12-16

申请号：US449980

申请日：1995-05-25

申请人： Sundeep Dugar ,  John W. Clader ,  Duane A. Burnett

发明人： Sundeep Dugar ,  John W. Clader ,  Duane A. Burnett

IPC分类号： A61K31/395 ,  A61K31/397 ,  A61K31/435 ,  A61K31/695 ,  A61P3/06 ,  A61P9/10 ,  C07D205/12 ,  C07D471/10 ,  C07F7/18 ,  C07D7/10

CPC分类号： C07D471/10 ,  C07D205/12

摘要： Novel compounds of the formula ##STR1## or a pharmaceutically acceptable salt thereof, wherein: R.sub.1 is ##STR2## R.sub.2 and R.sub.3 are independently selected from --CH.sub.2 --, --CH(lower alkyl)--, --C(di-lower alkyl)--, --CH.dbd.CH-- and --C(lower alkyl).dbd.CH--; or R.sub.1 with R.sub.2, or R.sub.1 with R.sub.3, form --CH.dbd.CH-- or --CH.dbd.C(lower alkyl)--; u and v are independently 0-3, provided both are not zero; R.sub.4 is B--(CH.sub.2).sub.m C(O)--; m is 0-5; B--(CH.sub.2).sub.q --; q is 0-6; B--(CH.sub.2).sub.e --Z--(CH.sub.2).sub.r ; Z is --O--, --C(O)--, phenylene, --N(R.sub.8)-- or --S(O).sub.0-2 --, e and r is 0-5; the sum of e and r is 0-6; B--(C.sub.2 -C.sub.6 alkenylene)--; B'--(C.sub.4 -C.sub.6 alkadienylene)--;B--(CH.sub.2).sub.t --Z--(C.sub.2 -C.sub.6 alkenylene)--; t is 0-3; the sum of t and the number of carbon atoms in the alkenylene chain is 2-6; B--(CH.sub.2).sub.f --V--(CH.sub.2).sub.g --; V is cycloalkylene, f is 1-5, g is 0-5; the sum of f and g is 1-6; B--(CH.sub.2).sub.t --V--(C.sub.2 -C.sub.6 alkenylene)-- or B'--(C.sub.2 -C.sub.6 alkenylene)--V--(CH.sub.2).sub.t --; the sum of t and the number of carbon atoms in the alkenylene chain is 2-6, B--(CH.sub.2).sub.a --Z--(CH.sub.2).sub.b --V--(CH.sub.2).sub.d --; a, b and d are 0-6; the sum of a, b and d is 0-6; T--(CH.sub.2).sub.s --; T is cycloalkyl, s is 0-6; or R.sub.1 and R.sub.4 together form ##STR3## B is optionally-substituted phenyl, indanyl, indenyl, naphthyl, tetrahydronaphthyl or optionally substituted-heteroaryl; and R.sub.20 and R.sub.21 are independently optionally-substituted phenyl, optionally-substituted naphthyl, indanyl, indenyl, tetrahydronaphthyl, benzodioxolyl, optionally-substituted heteroaryl, optionally-substituted benzofused heteroaryl or cyclopropyl, pharmaceutical compositions, the use as hypocholesterolemic agents, processes for preparing, and the use in combination with cholesterol biosynthesis inhibitors to treat or prevent athersclerosis.

摘要翻译： 式（I）的新化合物或其药学上可接受的盐，其中：R 1是R 2和R 3独立地选自-CH 2 - ， - CH（低级烷基） - ， - C（二 - 低级 烷基） - ， - CH = CH-和-C（低级烷基）= CH-; 或R1与R2，或R1与R3形成-CH = CH-或-CH = C（低级烷基） - ; u和v独立为0-3，两者都不为零; R4是B-（CH2）mC（O） - ; m为0-5; B-（CH2）q-; q为0-6; B-（CH 2）e-Z-（CH 2）r; Z是-O - ， - C（O） - ，亚苯基，-N（R 8） - 或-S（O）0-2-，e和r是0-5; e和r的和为0-6; B-（C 2 -C 6亚烯基） - ; B' - （C 4 -C 6链二烯） - ; B-（CH 2）t-Z-（C 2 -C 6亚烯基） - ; t为0-3; 亚烯基链中t和碳原子数之和为2-6; B-（CH2）f-V-（CH2）g-; V是亚环烷基，f是1-5，g是0-5; f和g之和为1-6; B-（CH2）t-V-（C2-C6亚链烯基） - 或B' - （C2-C6亚烯基）-V-（CH2）t-; 亚烯基链中t和碳原子数之和为2-6，B-（CH2）a-Z-（CH2）b-V-（CH2）d-; a，b和d为0-6; a，b和d的和为0-6; T（CH 2）s - ; T是环烷基，s是0-6; 或R 1和R 4一起形成B是任选取代的苯基，茚满基，茚基，萘基，四氢萘基或任选取代的杂芳基; R20和R21独立地是任选取代的苯基，任选取代的萘基，茚满基，茚基，四氢萘基，苯并二恶唑基，任选取代的杂芳基，任选取代的苯并稠合的杂芳基或环丙基，药物组合物，用作低胆固醇血症药， 以及与胆固醇生物合成抑制剂组合用于治疗或预防硬化症的用途。

公开(公告)号：US6043255A

公开(公告)日：2000-03-28

申请号：US266079

申请日：1999-03-10

申请人： Derek B. Lowe ,  Wei K. Chang ,  Joseph A. Kozlowski ,  Joel G. Berger ,  Robert McQuade ,  Allen Barnett ,  Margaret Sherlock ,  Wing Tom ,  Sundeep Dugar ,  Lian-Yong Chen ,  John W Clader ,  Samuel Chackalamannil ,  Yuguang Wang ,  Stuart W. McCombie ,  Jayaram R. Tagat ,  Susan F. Vice ,  Wayne Vaccaro ,  Michael J. Green ,  Margaret E. Browne ,  Theodros Asberom ,  Craig D. Boyle

发明人： Derek B. Lowe ,  Wei K. Chang ,  Joseph A. Kozlowski ,  Joel G. Berger ,  Robert McQuade ,  Allen Barnett ,  Margaret Sherlock ,  Wing Tom ,  Sundeep Dugar ,  Lian-Yong Chen ,  John W Clader ,  Samuel Chackalamannil ,  Yuguang Wang ,  Stuart W. McCombie ,  Jayaram R. Tagat ,  Susan F. Vice ,  Wayne Vaccaro ,  Michael J. Green ,  Margaret E. Browne ,  Theodros Asberom ,  Craig D. Boyle

IPC分类号： C07D211/58 ,  A61K31/00 ,  A61K31/435 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/496 ,  A61K31/50 ,  A61K31/501 ,  A61K45/00 ,  A61P25/28 ,  C07D211/24 ,  C07D211/32 ,  C07D211/96 ,  C07D239/34 ,  C07D257/04 ,  C07D295/02 ,  C07D295/03 ,  C07D295/084 ,  C07D295/088 ,  C07D295/096 ,  C07D295/112 ,  C07D295/116 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/145 ,  C07D295/15 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D401/02

CPC分类号： C07D405/14 ,  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 ,  C07C2101/14

摘要： Di-N-substituted piperazine or 1,4 di-substituted piperadine compounds in accordance with formula I (including all isomers, salts, esters, and solvates) ##STR1## wherein R, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.21, R.sup.27, R.sup.28, X, Y, and Z are 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1,4-二取代哌嗪化合物（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：US5744467A

公开(公告)日：1998-04-28

申请号：US813585

申请日：1997-01-08

申请人： Brian A. McKittrick ,  Sundeep Dugar ,  Duane A. Burnett

发明人： Brian A. McKittrick ,  Sundeep Dugar ,  Duane A. Burnett

IPC分类号： A61K31/395 ,  A61K31/397 ,  A61K31/44 ,  A61K31/4427 ,  A61K31/4433 ,  A61P3/06 ,  A61P9/10 ,  C07D205/08 ,  C07D401/12 ,  C07D409/12

CPC分类号： C07D401/12 ,  C07D205/08 ,  C07D409/12

摘要： Sulfur-substituted azetidinone hypocholesterolemic agents of the formula ##STR1## or a pharmaceutically acceptable salt thereof are disclosed, as well as pharmaceutical compositions containing them, and a method of lowering serum cholesterol by administering said compounds, alone or in combination with a cholesterol biosynthesis inhibitor.

摘要翻译： 公开了具有式“IMAGE”I的硫取代的氮杂环丁酮降胆固醇药或其药学上可接受的盐，以及含有它们的药物组合物，以及通过单独或与胆固醇生物合成组合施用所述化合物来降低血清胆固醇的方法 抑制剂。

公开(公告)号：US5624920A

公开(公告)日：1997-04-29

申请号：US342197

申请日：1994-11-18

申请人： Brian A. McKittrick ,  Sundeep Dugar ,  Duane A. Burnett

发明人： Brian A. McKittrick ,  Sundeep Dugar ,  Duane A. Burnett

IPC分类号： C07D205/08 ,  C07D401/12 ,  C07D409/12 ,  A61K31/395

CPC分类号： C07D401/12 ,  C07D205/08 ,  C07D409/12

摘要： Sulfur-substituted azetidinone hypocholesterolemic agents of the formula ##STR1## or a pharmaceutically acceptable salt thereof, wherein: Ar.sup.1 is aryl or R.sup.10 -substituted aryl;Ar.sup.2 is aryl or R.sup.4 -substituted aryl;Ar.sup.3 is aryl or R.sup.5 -substituted aryl;X and Y are --CH.sub.2 --, --CH(lower alkyl)-- or --C(dilower alkyl)--;R is --OR.sup.6, --O(CO)R.sup.6, --O(CO)OR.sup.9 or --O(CO)NR.sup.6 R.sup.7 ; R.sup.1 is hydrogen, lower alkyl or aryl; or R and R.sup.1 together are .dbd.O;q is 0 or 1; r is 0, 1 or 2; m and n are 0-5; provided that the sum of m, n and q is 1-5;R.sup.4 is selected from lower alkyl, --OR.sup.6, --O(CO)R.sup.6, --O(CO)OR.sup.9, --O(CH.sub.2).sub.1-5 OR.sup.6, --O(CO)NR.sup.6 R.sup.7, --NR.sup.6 R.sup.7, --NR.sup.6 (CO)R.sup.7, --NR.sup.6 (CO)OR.sup.9, --NR.sup.6 (CO)NR.sup.7 R.sup.8, --NR.sup.6 SO.sub.2 R.sup.9, --COOR.sup.6, --CONR.sup.6 R.sup.7, --COR.sup.6, --SO.sup.2 NR.sup.6 R.sup.7, S(O).sub.0-2 R.sup.9, --O(CH.sub.2).sub.1-10 --COOR.sup.6, --O(CH.sub.2).sub.1-10 CONR.sup.6 R.sup.7, --(lower alkylene)--COOR.sup.6 and --CH.dbd.CH--COOR.sup.6 ;R.sup.5 is selected from --OR.sup.6, --O(CO)R.sup.6, --O(CO)OR.sup.9, --O(CH.sub.2).sub.1-5 OR.sup.6, --O(CO)NR.sup.6 R.sup.7, --NR.sup.6 R.sup.7, --NR.sup.6 (CO)R.sup.7, --NR.sup.6 (CO)OR.sup.9, --NR.sup.6 (CO)NR.sup.7 R.sup.8, --NR.sup.6 SO.sub.2 R.sup.9, --COOR.sup.6, --CONR.sup.6 R.sup.7, --COR.sup.6, --SO.sub.2 NR.sup.6 R.sup.7, S(O).sub.0-2 R.sup.9, --O(CH.sub.2).sub.1-10 --COOR.sup.6, --O(CH.sub.2).sub.1-10 CONR.sup.6 R.sup.7, --CF.sub.3, --CN, --NO.sub.2, halogen, --(lower alkylene)COOR.sup.6 and --CH.dbd.CH--COOR.sup.6 ;R.sup.6, R.sup.7 and R.sup.8 are H, lower alkyl, aryl or aryl-substituted lower alkyl;R.sup.9 is lower alkyl, aryl or aryl-substituted lower alkyl; andR.sup.10 is selected from lower alkyl, --OR.sup.6, --O(CO)R.sup.6, --O(CO)OR.sup.9, --O(CH.sub.2).sub.1-5 OR.sup.6, --O(CO)NR.sup.6 R.sup.7, --NR.sup.6 R.sup.7, --NR.sup.6 (CO)R.sup.7, --NR.sup.6 (CO)OR.sup.9, --NR.sup.6 (CO)NR.sup.7 R.sup.8, --NR.sup.6 SO.sub.2 R.sup.9, --COOR.sup.6, --CONR.sup.6 R.sup.7, --COR.sup.6, --SO.sub.2 NR.sup.6 R.sup.7, S(O).sub.0-2 R.sup.9, --O(CH.sub.2).sub.1-10 --COOR.sup.6, --O(CH.sub.2).sub.1-10 CONR.sup.6 R.sup.7, --CF.sub.3, --CN, --NO.sub.2 and halogen;are disclosed, as well as pharmaceutical compositions containing them, and a method of lowering serum cholesterol by administering said compounds, alone or in combination with a cholesterol biosynthesis inhibitor.