公开(公告)号：US6127191A

公开(公告)日：2000-10-03

申请号：US980062

申请日：1997-11-26

Applicant: Todd L. Graybill ,  Zhengdong Wu ,  Nalin Subasinghe ,  Cynthia L. Fedde ,  Joseph M. Salvino

Inventor： Todd L. Graybill ,  Zhengdong Wu ,  Nalin Subasinghe ,  Cynthia L. Fedde ,  Joseph M. Salvino

IPC: C07B61/00 ,  C07C237/42 ,  C07C271/28 ,  C07C275/42 ,  C07C279/14 ,  C07C311/08 ,  C07C311/21 ,  C07C311/29 ,  C07C311/44 ,  C07C335/22 ,  C07D295/13 ,  C07D295/15 ,  C07J41/00 ,  C07C69/76 ,  C07C63/04 ,  C07C211/00

CPC classification number: C07D295/13 ,  C07C237/42 ,  C07C271/28 ,  C07C275/42 ,  C07C279/14 ,  C07C311/08 ,  C07C311/21 ,  C07C311/29 ,  C07C311/44 ,  C07C335/22 ,  C07D295/15 ,  C07J41/0055 ,  C40B40/04 ,  C40B50/14 ,  C07B2200/11 ,  C07C2101/02 ,  C07C2101/04 ,  C07C2101/08 ,  C07C2101/14 ,  C07C2103/74

Abstract: The present invention provides a library of compounds, each comprised of a common aminobenzenedicarboxylic acid core structure (scaffold) that serves as a template for synthesizing approximately 10.sup.1 -10.sup.6 compounds which are analogs of the scaffold. The library is employed to study ligand binding by biological receptors, such as enzymes, G-protein coupled receptors and membrane channels. For example, certain individual compounds within the library selectively bind and inhibit the action of trypsin-like serine proteases. The present invention also relates to combinatorial synthetic methods for making such libraries of compounds. Additionally, the present invention relates to novel scaffold-modified solid supports, particularly scaffold-modified polymer resins and methods for preparing said resins. Further, the present invention is directed to methods for screening a compound or plurality of compounds made according to the synthetic methods disclosed herein, which comprise using the compounds in suitable assays developed for detecting the compounds' utility as pharmaceutical agents.

Abstract translation: 本发明提供了一种化合物文库，每一种化合物均由常用的氨基苯二甲酸核心结构（支架）组成，其用作合成大约101-106个作为支架类似物的化合物的模板。 该文库用于研究配体结合生物受体，如酶，G蛋白偶联受体和膜通道。 例如，文库中的某些单个化合物选择性地结合并抑制胰蛋白酶样丝氨酸蛋白酶的作用。 本发明还涉及制备这种化合物文库的组合合成方法。 另外，本发明涉及新的支架改性固体支持物，特别是支架改性的聚合物树脂以及制备所述树脂的方法。 此外，本发明涉及用于筛选根据本文公开的合成方法制备的化合物或多种化合物的方法，其包括在合适的测定中使用该化合物，其用于检测化合物作为药剂的效用。

公开(公告)号：US08518969B2

公开(公告)日：2013-08-27

申请号：US13161572

申请日：2011-06-16

Applicant: James C. Lanter ,  Thomas P. Markotan ,  Nalin Subasinghe ,  Zhihua Sui

Inventor： James C. Lanter ,  Thomas P. Markotan ,  Nalin Subasinghe ,  Zhihua Sui

IPC: A01N43/42 ,  A61K31/47

CPC classification number: C07D471/04 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/502 ,  A61K31/517 ,  A61K31/5377 ,  A61K31/541 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention comprises compounds of Formula I. wherein: R1, R2, R4, J, Q, and A are as defined in the specification. The invention also comprises a method of preventing, treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is type II diabetes, obesity and asthma. The invention also comprises a method of inhibiting CCR2 activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula I.

公开(公告)号：US07109354B2

公开(公告)日：2006-09-19

申请号：US10445817

申请日：2003-05-28

Applicant: Nalin Subasinghe ,  Ehab Khalil ,  Kristi Leonard ,  Farah Ali ,  Heather Rae Hufnagel ,  Jeremy M. Travins ,  Shelley K. Ballentine ,  Kenneth T. Wilson ,  Maxwell D. Cummings ,  Wenxi Pan ,  Joan Gushue ,  Sanath Meegalla ,  Mark Wall ,  Jinsheng Chen ,  M. Jonathan Rudolph ,  Hui Huang

Inventor： Nalin Subasinghe ,  Ehab Khalil ,  Kristi Leonard ,  Farah Ali ,  Heather Rae Hufnagel ,  Jeremy M. Travins ,  Shelley K. Ballentine ,  Kenneth T. Wilson ,  Maxwell D. Cummings ,  Wenxi Pan ,  Joan Gushue ,  Sanath Meegalla ,  Mark Wall ,  Jinsheng Chen ,  M. Jonathan Rudolph ,  Hui Huang

IPC: C07D333/02 ,  C07D333/32

CPC classification number: C07D417/12 ,  C07D333/38 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D495/04 ,  C07F7/0812 ,  C07F9/655345

Abstract: Disclosed is a method for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4 and R7 are defined in the specification, Z is SO or SO2, and Ar is an aromatic or heteroaromatic group as defined herein.

Abstract translation: 公开了一种治疗由补体级联的经典途径介导的急性或慢性病症症状的方法，其包括向需要这种治疗的哺乳动物施用治疗有效量的式I化合物或溶剂合物，水合物或 其药学上可接受的盐; 其中R 1，R 2，R 3，R 4和R 7， 在本说明书中定义，Z是SO或SO 2，Ar是如本文所定义的芳族或杂芳族基团。

公开(公告)号：US20050234081A1

公开(公告)日：2005-10-20

申请号：US10515554

申请日：2003-05-28

Applicant: Nalin Subasinghe ,  Ehab Khalil ,  Kristi Leonard ,  Farah Ali ,  Heather Hufnagel ,  Jeremy Travins ,  Shelley Ballentine ,  Kenneth Wilson ,  Maxwell Cummings ,  Wenxi Pan ,  Joan Gushue ,  Sanath Meegalla ,  Mark Wall ,  Jinsheng Chen

Inventor： Nalin Subasinghe ,  Ehab Khalil ,  Kristi Leonard ,  Farah Ali ,  Heather Hufnagel ,  Jeremy Travins ,  Shelley Ballentine ,  Kenneth Wilson ,  Maxwell Cummings ,  Wenxi Pan ,  Joan Gushue ,  Sanath Meegalla ,  Mark Wall ,  Jinsheng Chen

IPC: C07D333/22 ,  A61K31/381 ,  A61K31/404 ,  A61K31/41 ,  A61K31/416 ,  A61K31/4178 ,  A61K31/4184 ,  A61K31/4188 ,  A61K31/422 ,  A61K31/427 ,  A61K31/428 ,  A61K31/4436 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4535 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/497 ,  A61K31/506 ,  A61K31/513 ,  A61K31/5377 ,  A61K31/662 ,  A61P1/04 ,  A61P3/10 ,  A61P5/14 ,  A61P5/48 ,  A61P7/00 ,  A61P7/06 ,  A61P7/08 ,  A61P7/10 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P13/02 ,  A61P13/12 ,  A61P17/00 ,  A61P17/02 ,  A61P17/06 ,  A61P19/02 ,  A61P19/10 ,  A61P21/04 ,  A61P25/00 ,  A61P25/28 ,  A61P29/00 ,  A61P31/00 ,  A61P31/04 ,  A61P37/00 ,  A61P37/06 ,  A61P37/08 ,  A61P41/00 ,  A61P43/00 ,  C07D333/12 ,  C07D333/38 ,  C07D333/54 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D495/04 ,  C07F7/08 ,  C07F7/10 ,  C07F9/6553 ,  C07D49/02

CPC classification number: C07D417/12 ,  C07D333/38 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D495/04 ,  C07F7/0812 ,  C07F9/655345

Abstract: Disclosed is a method for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula (I) or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4 and R7 are defined in the specification, Z is SO or SO2, and Ar is an aromatic or heteroaromatic group as defined herein.

Abstract translation: 公开了一种治疗由补体级联的经典途径介导的急性或慢性病症症状的方法，包括向需要这种治疗的哺乳动物施用治疗有效量的式（I）化合物或溶剂合物， 水合物或其药学上可接受的盐; 其中R 1，R 2，R 3，R 4和R 7， 在本说明书中定义，Z是SO或SO 2，Ar是如本文所定义的芳族或杂芳族基团。

公开(公告)号：US20050004031A1

公开(公告)日：2005-01-06

申请号：US10869430

申请日：2004-06-16

Applicant: Nalin Subasinghe ,  Ehab Khalil ,  Farah Ali ,  Heather Hufnagel ,  Shelley Ballentine ,  Jeremy Travins ,  Kristi Leonard ,  Roger Bone

Inventor： Nalin Subasinghe ,  Ehab Khalil ,  Farah Ali ,  Heather Hufnagel ,  Shelley Ballentine ,  Jeremy Travins ,  Kristi Leonard ,  Roger Bone

IPC: A61K47/48 ,  A61K38/17

CPC classification number: A61K47/60

Abstract: The present invention is directed to conjugated complement cascade inhibitors, and a method of treating a patient using a conjugated complement cascade inhibitor.

Abstract translation: 本发明涉及缀合的补体级联抑制剂，以及使用缀合的补体级联抑制剂治疗患者的方法。

公开(公告)号：US20110312936A1

公开(公告)日：2011-12-22

申请号：US13161572

申请日：2011-06-16

Applicant: James C. Lanter ,  Thomas P. Markotan ,  Nalin Subasinghe ,  Zhihua Sui

Inventor： James C. Lanter ,  Thomas P. Markotan ,  Nalin Subasinghe ,  Zhihua Sui

IPC: A61K31/4725 ,  A61K31/517 ,  A61K31/4709 ,  A61P35/00 ,  A61P35/02 ,  C07D413/14 ,  A61P25/00 ,  C07D403/12 ,  A61P9/00 ,  C07D471/04 ,  A61K31/502 ,  A61P19/00 ,  C07D405/14 ,  C07D403/14 ,  C07D401/14 ,  A61K31/5377 ,  C07D417/14 ,  A61P29/00 ,  A61P11/00 ,  A61P27/02 ,  A61P19/02 ,  A61P17/06 ,  A61P17/00 ,  A61P3/10 ,  A61P3/04 ,  A61P3/00 ,  A61P31/06 ,  A61P37/08 ,  A61P41/00 ,  A61P25/28 ,  A61K31/541

CPC classification number: C07D471/04 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/502 ,  A61K31/517 ,  A61K31/5377 ,  A61K31/541 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention comprises compounds of Formula I. wherein: R1, R2, R4, J, Q, and A are as defined in the specification. The invention also comprises a method of preventing, treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is type II diabetes, obesity and asthma. The invention also comprises a method of inhibiting CCR2 activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula I.

Abstract translation: 本发明包括式I化合物，其中：R1，R2，R4，J，Q和A如说明书中所定义。 本发明还包括预防，治疗或改善综合征，病症或疾病的方法，其中所述综合征，病症或疾病是II型糖尿病，肥胖症和哮喘。 本发明还包括通过施用治疗有效量的至少一种式I化合物来抑制哺乳动物CCR2活性的方法。

公开(公告)号：US07482376B2

公开(公告)日：2009-01-27

申请号：US10869430

申请日：2004-06-16

Applicant: Nalin Subasinghe ,  Ehab Khalil ,  Farah Ali ,  Heather Rae Hufnagel ,  Shelley Ballentine ,  Jeremy M. Travins ,  Kristi A. Leonard ,  Roger F. Bone

Inventor： Nalin Subasinghe ,  Ehab Khalil ,  Farah Ali ,  Heather Rae Hufnagel ,  Shelley Ballentine ,  Jeremy M. Travins ,  Kristi A. Leonard ,  Roger F. Bone

IPC: A61K31/381 ,  C07D333/10

CPC classification number: A61K47/60

Abstract: The present invention is directed to conjugated complement cascade inhibitors, and a method of treating a patient using a conjugated complement cascade inhibitor.

Abstract translation: 本发明涉及缀合的补体级联抑制剂，以及使用缀合的补体级联抑制剂治疗患者的方法。

公开(公告)号：US20070066667A1

公开(公告)日：2007-03-22

申请号：US11375503

申请日：2006-03-14

Applicant: Nalin Subasinghe ,  Shelley Ballentine ,  Jeremy Travins ,  Ehab Khalil ,  Farah Ali ,  Kristi Leonard ,  Joan Gushue ,  Michael Winters ,  Heather Hufnagel ,  Maxwell Cummings

Inventor： Nalin Subasinghe ,  Shelley Ballentine ,  Jeremy Travins ,  Ehab Khalil ,  Farah Ali ,  Kristi Leonard ,  Joan Gushue ,  Michael Winters ,  Heather Hufnagel ,  Maxwell Cummings

IPC: A61K31/422 ,  A61K31/381 ,  C07D413/02 ,  C07D333/16

CPC classification number: C07D413/12 ,  C07D333/38 ,  C07D409/12 ,  C07D417/12

Abstract: Disclosed are compounds for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade. Said compounds are of Formula I or a solvate, hydrate, pharmaceutically acceptable salt, or prodrug thereof; wherein Ra, Rb, and Rc are defined in the specification, as are A Z, Q, R1 and R2.

Abstract translation: 公开了用于治疗由补体级联的经典途径介导的急性或慢性病症症状的化合物。 所述化合物具有式I或其溶剂化物，水合物，药学上可接受的盐或前药; 其中R a，R b和R c在本说明书中定义，AZ，Q，R 1， SUP>和R 2 2。

公开(公告)号：US08921559B2

公开(公告)日：2014-12-30

申请号：US13307357

申请日：2011-11-30

Applicant: James C. Lanter ,  Thomas P. Markotan ,  Nalin Subasinghe ,  Zhihua Sui ,  Xuqing Zhang

Inventor： James C. Lanter ,  Thomas P. Markotan ,  Nalin Subasinghe ,  Zhihua Sui ,  Xuqing Zhang

IPC: C07D471/04 ,  C07D401/12 ,  A61K31/437 ,  A61K31/4545 ,  A61K31/454 ,  C07D405/14

CPC classification number: C07D401/12 ,  C07D405/14 ,  C07D471/04

Abstract: The present invention comprises compounds of Formula (I). wherein: R1, R2, R3, R4, X, Y, and Z are as defined in the specification. The invention also comprises a method of preventing, treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is type II diabetes, obesity and asthma. The invention also comprises a method of inhibiting CCR2 activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula (I).

Abstract translation: 本发明包括式（I）的化合物。 其中：R1，R2，R3，R4，X，Y和Z如说明书中所定义。 本发明还包括预防，治疗或改善综合征，病症或疾病的方法，其中所述综合征，病症或疾病是II型糖尿病，肥胖症和哮喘。 本发明还包括通过施用治疗有效量的至少一种式（I）化合物来抑制哺乳动物CCR2活性的方法。

公开(公告)号：US20120142733A1

公开(公告)日：2012-06-07

申请号：US13307357

申请日：2011-11-30

Applicant: James C. Lanter ,  Thomas P. Markotan ,  Nalin Subasinghe ,  Zhihua Sui ,  Xuqing Zhang

Inventor： James C. Lanter ,  Thomas P. Markotan ,  Nalin Subasinghe ,  Zhihua Sui ,  Xuqing Zhang

IPC: A61K31/454 ,  C07D405/14 ,  C07D471/04 ,  A61K31/4545 ,  A61P11/00 ,  A61P27/02 ,  A61P29/00 ,  A61P17/06 ,  A61P19/02 ,  A61P17/00 ,  A61P25/00 ,  A61P1/00 ,  A61P1/04 ,  A61P13/12 ,  A61P37/06 ,  A61P3/10 ,  A61P3/04 ,  A61P5/48 ,  A61P3/00 ,  A61P31/06 ,  A61P37/08 ,  A61P27/14 ,  A61P11/06 ,  A61P1/02 ,  A61P9/00 ,  A61P9/10 ,  A61P9/04 ,  A61P35/00 ,  A61P35/02 ,  C07D401/12

CPC classification number: C07D401/12 ,  C07D405/14 ,  C07D471/04

Abstract: The present invention comprises compounds of Formula (I). wherein: R1, R2, R3, R4, X, Y, and Z are as defined in the specification. The invention also comprises a method of preventing, treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is type II diabetes, obesity and asthma. The invention also comprises a method of inhibiting CCR2 activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula (I).

Abstract translation: 本发明包括式（I）的化合物。 其中：R1，R2，R3，R4，X，Y和Z如说明书中所定义。 本发明还包括预防，治疗或改善综合征，病症或疾病的方法，其中所述综合征，病症或疾病是II型糖尿病，肥胖症和哮喘。 本发明还包括通过施用治疗有效量的至少一种式（I）化合物来抑制哺乳动物CCR2活性的方法。