公开(公告)号：US4973586A

公开(公告)日：1990-11-27

申请号：US223739

申请日：1988-07-18

申请人： Joel G. Berger ,  Wei K. Chang ,  Elijah H. Gold ,  John W. Clader

发明人： Joel G. Berger ,  Wei K. Chang ,  Elijah H. Gold ,  John W. Clader

IPC分类号： C07D223/14 ,  A61K31/55 ,  A61K31/675 ,  A61P25/30 ,  A61P39/02 ,  C07D223/32 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D491/04 ,  C07D491/044 ,  C07D491/052 ,  C07D495/04 ,  C07D495/14 ,  C07F9/553 ,  C07F9/6561

CPC分类号： C07D223/14 ,  A61K31/55 ,  C07D491/04

摘要： Disclosed are fused benzazepine compounds, pharmaceutical compositions including such compounds, methods of using such compounds, for example, in the treatment of psychoses and/or depression, and intermediates useful in the preparation of such compounds.

摘要翻译： 公开了稠合苯并氮杂化合物，包括这些化合物的药物组合物，使用这些化合物的方法，例如治疗精神病和/或抑郁症，以及可用于制备这些化合物的中间体。

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：US20110054013A1

公开(公告)日：2011-03-03

申请号：US12869010

申请日：2010-08-26

申请人： John W. Clader

发明人： John W. Clader

IPC分类号： A61K31/382 ,  C07D493/04 ,  A61P25/28

CPC分类号： A61K31/382 ,  C07D311/80 ,  C07D407/12 ,  C07D493/04

摘要： Disclosed are novel gamma secretase inhibitors of the formula: wherein at least one (e.g., 1-4, 1-3, 1-2, 2 or 1) H is replaced by deuterium. Also disclosed are methods of inhibiting gamma-secretase, methods of treating neurodegenerative diseases, and methods of treating Alzheimer's Disease.

摘要翻译： 公开了下式的新型γ分泌酶抑制剂：其中至少一个（例如，1-4,1-3,1-2,2或1）H被氘代替。 还公开了抑制γ-分泌酶，治疗神经变性疾病的方法和治疗阿尔茨海默氏病的方法。

公开(公告)号：US20080207585A1

公开(公告)日：2008-08-28

申请号：US12107112

申请日：2008-04-22

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

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

IPC分类号： A61K31/397 ,  C07D205/08 ,  A61P9/10

CPC分类号： C07D403/12 ,  C07D205/08 ,  Y10S930/28

摘要： The present invention provides compounds represented by the structural formula (I): or pharmaceutically acceptable isomers, salts, solvates or esters of the compound of Formula (I), wherein each of the substituents is as specified herein, formulations including the above compounds, processes for preparing the same and methods for treating atherosclerosis, hypercholesterolemia, or sitosterolemia, and for lowering plasma levels of sterols and/or stanols.

公开(公告)号：US06689783B2

公开(公告)日：2004-02-10

申请号：US10107992

申请日：2002-03-27

申请人： John W. Clader ,  Sue-Ing Y. Lin ,  Stuart W. Mc Combie ,  Pradeep B. Pushpavanam ,  Susan Vice

发明人： John W. Clader ,  Sue-Ing Y. Lin ,  Stuart W. Mc Combie ,  Pradeep B. Pushpavanam ,  Susan Vice

IPC分类号： A61K31496

CPC分类号： C07D401/06

摘要： In one embodiment, this invention provides a novel class of aryl oxime-piperazine compounds as antagonists of the CCR5 receptor, methods of preparing such compounds, pharmaceutical compositions containing one or more of the compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention or amelioration of one or more of diseases associated with the CCR5 receptor. An illustrative inventive compound is shown below:

摘要翻译： 在一个实施方案中，本发明提供了作为CCR5受体拮抗剂的新型芳基肟 - 哌嗪化合物，制备此类化合物的方法，含有一种或多种化合物的药物组合物，制备包含一种或多种这类化合物的药物制剂的方法 以及治疗，预防或改善与CCR5受体相关的一种或多种疾病的方法。 示例性的本发明化合物如下所示：

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：US5238950A

公开(公告)日：1993-08-24

申请号：US808997

申请日：1991-12-17

申请人： John W. Clader ,  Harry R. Davis ,  Deborra Mullins ,  Stuart Rosenblum ,  Jay Weinstein

发明人： John W. Clader ,  Harry R. Davis ,  Deborra Mullins ,  Stuart Rosenblum ,  Jay Weinstein

IPC分类号： C07D207/48 ,  C07D209/48 ,  C07D487/04

CPC分类号： C07D209/48 ,  C07D207/48 ,  C07D487/04

摘要： A method of inhibiting the binding of PDGF using compounds of the formula I ##STR1## useful in the treatment of atherosclerosis, cancer, retinal detachment, pulmonary fibrosis, arthritis, psoriasis and glomerulonephritis, and restenosis following angioplasty or vascular surgery is disclosed.Also disclosed are pharmaceutical compositions and novel PDGF inhibitory compounds of the formula ##STR2## or a pharmaceutically acceptable addition salt thereof, useful in the treatment of atherosclerosis, cancer, retinal detachment, pulmonary fibrosis, arthritis, psoriasis and glomerulonephritis, and restenosis following angioplasty or vascular surgery.

摘要翻译： 公开了使用可用于治疗动脉粥样硬化，癌症，视网膜脱离，肺纤维化，关节炎，牛皮癣和肾小球性肾炎的化学式I的化合物和血管成形术或血管手术后的再狭窄来抑制PDGF的结合的方法。 还公开了可用于治疗动脉粥样硬化，癌症，视网膜脱离，肺纤维化，关节炎，牛皮癣和肾小球性肾炎的药物组合物和新颖的具有式“IMAGE”或其药学上可接受的加成盐的PDGF抑制化合物，以及血管成形术后的再狭窄或 血管手术。