公开(公告)号：US20080269499A1

公开(公告)日：2008-10-30

申请号：US12130915

申请日：2008-05-30

申请人： Albert J. DelMonte ,  T.G. Murali Dhar ,  Yu Fan ,  Jack Z. Gougoutas ,  Mary F. Malley ,  Douglas D. McLeod ,  Robert E. Waltermire ,  Chenkou Wei

发明人： Albert J. DelMonte ,  T.G. Murali Dhar ,  Yu Fan ,  Jack Z. Gougoutas ,  Mary F. Malley ,  Douglas D. McLeod ,  Robert E. Waltermire ,  Chenkou Wei

IPC分类号： C07D487/10

CPC分类号： C07D487/10

摘要： A process is provided for preparing spiro-hydantoin compounds of the formula II wherein Z is N or CR4b; K and L are independently O or S; Ar is an optionally substituted aryl or heteroaryl; A2 is a linker, G′ is a linker; Q is a linker; and R2, R4a, R4c, and Rh are defined in the specification. The process optionally includes the enantiomeric separation of intermediates to allow preparation of enantiomers of the spiro-hydantoin compounds of formula II. Substituted spiro-hydantoin compounds may be prepared from the spiro-hydantoin compounds of formula II. The spiro-hydantoin compound of formula II and the substituted spiro-hydantoin compounds are useful in the treatment of immune or inflammatory diseases. Also, provided are products made by the instant inventive process and crystalline forms (prepared by any process) of the substituted spiro-hydantoin compound, 5-[(5S,9R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-ylmethyl]-thiophene-3-carboxylic acid, including solvates and salts thereof, as well as methods of use thereof. Crystalline forms of certain intermediates are provided.

摘要翻译： 提供了制备式II的螺 - 乙内酰脲化合物的方法，其中Z是N或CR 4b; K和L独立地为O或S; Ar是任选取代的芳基或杂芳基; A 2是连接体，G'是连接体; Q是一个连接符; 和R 2，R 4a，R 4c和R h H在本说明书中定义。 该方法任选地包括中间体的对映异构体分离，以允许制备式II的螺 - 乙内酰脲化合物的对映异构体。 取代的螺 - 乙内酰脲化合物可以由式II的螺 - 乙内酰脲化合物制备。 式II的螺 - 乙内酰脲化合物和取代的螺 - 乙内酰脲化合物可用于治疗免疫或炎性疾病。 此外，提供的是本发明方法制备的产物和取代的螺 - 乙内酰脲化合物的5 - [（5S，9R）-9-（4-氰基苯基）-3-（3， 5-二氯苯基）-1-甲基-2,4-二氧代-1,3,7-三氮杂螺[4.4]壬-7-基甲基] - 噻吩-3-甲酸，包括其溶剂合物及其盐，以及 使用它。 提供某些中间体的结晶形式。

公开(公告)号：US07381737B2

公开(公告)日：2008-06-03

申请号：US11238427

申请日：2005-09-29

申请人： Albert J. DelMonte ,  T. G. Murali Dhar ,  Yu Fan ,  Jack Z. Gougoutas ,  Mary F. Malley ,  Douglas D. McLeod ,  Robert E. Waltermire ,  Chenkou Wei

发明人： Albert J. DelMonte ,  T. G. Murali Dhar ,  Yu Fan ,  Jack Z. Gougoutas ,  Mary F. Malley ,  Douglas D. McLeod ,  Robert E. Waltermire ,  Chenkou Wei

IPC分类号： A61K31/4188 ,  C07D235/00

CPC分类号： C07D487/10

摘要： A process is provided for preparing spiro-hydantoin compounds of the formula II wherein Z is N or CR4b; K and L are independently O or S; Ar is an optionally substituted aryl or heteroaryl; A2 is a linker, G′ is a linker; Q is a linker; and R2, R4a, R4c, and Rh are defined in the specification. The process optionally includes the enantiomeric separation of intermediates to allow preparation of enantiomers of the spiro-hydantoin compounds of formula II. Substituted spiro-hydantoin compounds may be prepared from the spiro-hydantoin compounds of formula II. The spiro-hydantoin compound of formula II and the substituted spiro-hydantoin compounds are useful in the treatment of immune or inflammatory diseases. Also, provided are products made by the instant inventive process and crystalline forms (prepared by any process) of the substituted spiro-hydantoin compound, 5-[(5S,9R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-ylmethyl]-thiophene-3-carboxylic acid, including solvates and salts thereof, as well as methods of use thereof. Crystalline forms of certain intermediates are provided.

摘要翻译： 提供了制备式II的螺 - 乙内酰脲化合物的方法，其中Z是N或CR 4b; K和L独立地为O或S; Ar是任选取代的芳基或杂芳基; A 2是连接体，G'是连接体; Q是一个连接符; 和R 2，R 4a，R 4c和R h H在本说明书中定义。 该方法任选地包括中间体的对映异构体分离，以允许制备式II的螺 - 乙内酰脲化合物的对映异构体。 取代的螺 - 乙内酰脲化合物可以由式II的螺 - 乙内酰脲化合物制备。 式II的螺 - 乙内酰脲化合物和取代的螺 - 乙内酰脲化合物可用于治疗免疫或炎性疾病。 此外，提供的是本发明方法制备的产物和取代的螺 - 乙内酰脲化合物的5 - [（5S，9R）-9-（4-氰基苯基）-3-（3， 5-二氯苯基）-1-甲基-2,4-二氧代-1,3,7-三氮杂螺[4.4]壬-7-基甲基] - 噻吩-3-甲酸，包括其溶剂合物及其盐，以及 使用它。 提供某些中间体的结晶形式。

公开(公告)号：US4673900A

公开(公告)日：1987-06-16

申请号：US727036

申请日：1985-04-25

申请人： Michael F. Blamire ,  Peter F. Briscoe ,  Douglas D. McLeod ,  B. Kingsley Doolittle ,  Michael J. Roach

发明人： Michael F. Blamire ,  Peter F. Briscoe ,  Douglas D. McLeod ,  B. Kingsley Doolittle ,  Michael J. Roach

IPC分类号： H01G4/224 ,  H01G4/40 ,  H03H1/00 ,  H03H7/01 ,  H01G7/00

CPC分类号： H01G4/224 ,  H01G4/40 ,  H03H1/0007 ,  Y10T29/435

摘要： The invention provides a novel attachment for a discoid capacitor and the like to the inside of a tubular casing and to a central lead. An electrically insulating sealing element is positioned below the capacitor during assembly vertically into the casing. The element fits closely about the lead and is deformed into contact with the wall of the housing about the capacitor. The element thus forms a dam to contain solder and flux used to couple the capacitor to the lead and to the casing from above the capacitor so that the solder and flux cannot pass by the capacitor into undesirable locations below the capacitor.

摘要翻译： 本发明提供了一种用于盘状电容器等到管状外壳和中心引线的内部的新型附件。 电绝缘的密封元件位于电容器的正下方，装配在壳体内。 该元件紧密地配合在引线周围，并且变形为与壳体的围绕电容器的壁接触。 元件因此形成一个大坝，以容纳用于将电容器连接到电感器上的电容器和壳体的焊料和焊剂，使得焊料和焊剂不能通过电容器到电容器下方的不期望的位置。

公开(公告)号：US06835841B2

公开(公告)日：2004-12-28

申请号：US10660345

申请日：2003-09-11

申请人： Joerg Deerberg ,  Douglas D. McLeod ,  Tai-Yuen Yue

发明人： Joerg Deerberg ,  Douglas D. McLeod ,  Tai-Yuen Yue

IPC分类号： C07D21158

CPC分类号： C07D317/72 ,  C07D211/60 ,  C07D309/08

摘要： A novel process for the asymmetric synthesis of substituted cyclic &bgr;-amino-carboxylates of the type shown in the specification from appropriate &bgr;-enamino-ester starting materials is described. These compounds are useful as intermediates for MMP and TACE inhibitors.

摘要翻译： 描述了从合适的β-烯氨基酯起始原料不规则合成说明书中所示类型的取代的环状β-氨基 - 羧酸盐的新方法。 这些化合物可用作MMP和TACE抑制剂的中间体。