公开(公告)号：US08450317B2

公开(公告)日：2013-05-28

申请号：US12768268

申请日：2010-04-27

Applicant: Jennifer A. Kowalski ,  Daniel Richard Marshall ,  Anthony S. Prokopowicz, III ,  Sabine Schlyer ,  Robert Sibley ,  Ronald John Sorcek ,  Di Wu ,  Frank Wu ,  Erick Richard Roush Young

Inventor： Jennifer A. Kowalski ,  Daniel Richard Marshall ,  Anthony S. Prokopowicz, III ,  Sabine Schlyer ,  Robert Sibley ,  Ronald John Sorcek ,  Di Wu ,  Frank Wu ,  Erick Richard Roush Young

IPC: C07D239/34 ,  C07D239/42 ,  A61K31/506

CPC classification number: C07D471/04 ,  C07D209/48 ,  C07D213/26 ,  C07D213/56 ,  C07D213/65 ,  C07D213/74 ,  C07D217/00 ,  C07D231/10 ,  C07D233/90 ,  C07D235/04 ,  C07D239/34 ,  C07D239/42 ,  C07D277/30 ,  C07D295/185 ,  C07D307/68 ,  C07D317/68 ,  C07D319/18 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D413/12 ,  C07D417/12 ,  C07D491/08

Abstract: The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R1 to R5, A, B, D and X are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

Abstract translation: 本发明涉及式（I）化合物及其药学上可接受的盐，其中R 1至R 5，A，B，D和X如本文所定义。 本发明还涉及包含这些化合物的药物组合物，使用这些化合物治疗各种疾病和病症的方法，制备这些化合物的方法和可用于这些方法的中间体。

公开(公告)号：US08420630B2

公开(公告)日：2013-04-16

申请号：US12711364

申请日：2010-02-24

Applicant: Georg Dahmann ,  Frank Himmelsbach ,  Bernd Krist ,  Martin Lenter ,  Alexander Pautsch ,  Gisela Schnapp ,  Martin Steegmaier ,  Helmut Wittneben ,  Anthony S. Prokopowicz ,  Walter Spevak ,  Andreas Schoop ,  Steffen Steurer

Inventor： Georg Dahmann ,  Frank Himmelsbach ,  Bernd Krist ,  Martin Lenter ,  Alexander Pautsch ,  Gisela Schnapp ,  Martin Steegmaier ,  Helmut Wittneben ,  Anthony S. Prokopowicz ,  Walter Spevak ,  Andreas Schoop ,  Steffen Steurer

IPC: C07D239/48 ,  C07D403/12 ,  C07D401/12 ,  A61K31/506

CPC classification number: C07D239/48 ,  C07D231/12 ,  C07D233/56 ,  C07D239/50 ,  C07D239/80 ,  C07D249/08 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D451/04 ,  C07D451/06 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  C07D487/10

Abstract: The present invention relates to trisubstituted pyrimidines of formula (I) wherein 0Ra to Re are defined as in claim 1, which are suitable for the treatment of illnesses characterized by excessive or abnormal cell proliferation, the use thereof for preparing a pharmaceutical composition with the abovementioned properties, and processes for the preparation thereof.

Abstract translation: 本发明涉及式（I）的三取代嘧啶，其中0Ra至Re如权利要求1所定义，其适用于治疗以细胞增殖过度或异常为特征的疾病，其用于制备具有上述药物组合物的用途 性质及其制备方法。

公开(公告)号：US06844435B2

公开(公告)日：2005-01-18

申请号：US10271222

申请日：2002-10-15

Applicant: Roger John Snow ,  Donghong A. Gao ,  Daniel R. Goldberg ,  Abdelhakim Hammach ,  Daniel Kuzmich ,  Tina Marie Morwick ,  Neil Moss ,  Anthony S. Prokopowicz, III ,  Robert D. Selliah ,  Hidenori Takahashi

Inventor： Roger John Snow ,  Donghong A. Gao ,  Daniel R. Goldberg ,  Abdelhakim Hammach ,  Daniel Kuzmich ,  Tina Marie Morwick ,  Neil Moss ,  Anthony S. Prokopowicz, III ,  Robert D. Selliah ,  Hidenori Takahashi

IPC: A61K31/517 ,  A61P1/04 ,  A61P3/10 ,  A61P9/00 ,  A61P9/10 ,  A61P11/06 ,  A61P17/06 ,  A61P19/02 ,  A61P19/08 ,  A61P25/00 ,  A61P35/00 ,  A61P37/02 ,  A61P37/06 ,  A61P43/00 ,  C07D487/04 ,  C07D235/14

CPC classification number: C07D487/04 ,  A61K31/517

Abstract: Disclosed are novel compounds of formula (I): wherein Ar1, X, Y, P, Q and Het are defined herein, which are useful as inhibitors of certain protein tyrosine kinases and are thus useful for treating diseases resulting from inappropriate cell proliferation, which include autoimmune diseases, chronic inflammatory diseases, allergic diseases, transplant rejection and cancer, as well as conditions resulting from cerebral ischemia, such as stroke. Also disclosed are pharmaceutical compositions comprising these compounds, processes for preparing these compounds and novel intermediate compounds useful in these processes.

Abstract translation: 公开了式（I）的新化合物：其中Ar1，X，Y，P，Q和Het在本文中定义，其可用作某些蛋白酪氨酸激酶的抑制剂，因此可用于治疗由不适当的细胞增殖引起的疾病， 包括自身免疫性疾病，慢性炎症性疾病，过敏性疾病，移植排斥和癌症，以及由脑缺血引起的病症，例如中风。 还公开了包含这些化合物的药物组合物，制备这些化合物的方法和用于这些方法的新型中间体化合物。

公开(公告)号：US20100152167A1

公开(公告)日：2010-06-17

申请号：US12711364

申请日：2010-02-24

Applicant: Georg DAHMANN ,  Frank HIMMELSBACH ,  Bernd KRIST ,  Martin LENTER ,  Alexander PAUTSCH ,  Gisela SCHNAPP ,  Martin STEEGMAIER ,  Helmut WITTNEBEN ,  Anthony S. PROKOPOWICZ ,  Walter SPEVAK ,  Andreas SCHOOP ,  Steffen STEURER

Inventor： Georg DAHMANN ,  Frank HIMMELSBACH ,  Bernd KRIST ,  Martin LENTER ,  Alexander PAUTSCH ,  Gisela SCHNAPP ,  Martin STEEGMAIER ,  Helmut WITTNEBEN ,  Anthony S. PROKOPOWICZ ,  Walter SPEVAK ,  Andreas SCHOOP ,  Steffen STEURER

IPC: A61K31/505 ,  C07D239/50 ,  C07D413/12 ,  A61K31/5377 ,  A61K31/506 ,  C07D403/04 ,  A61K31/55 ,  C07D403/12 ,  A61K31/551 ,  A61P31/00 ,  A61P35/00 ,  A61P9/00 ,  A61P19/08

CPC classification number: C07D239/48 ,  C07D231/12 ,  C07D233/56 ,  C07D239/50 ,  C07D239/80 ,  C07D249/08 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D451/04 ,  C07D451/06 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  C07D487/10

Abstract: The present invention relates to trisubstituted pyrimidines of formula (I) wherein0Ra to Re are defined as in claim 1, which are suitable for the treatment of illnesses characterised by excessive or abnormal cell proliferation, the use thereof for preparing a pharmaceutical composition with the abovementioned properties, and processes for the preparation thereof.

Abstract translation: 本发明涉及式（I）的三取代嘧啶，其中0Ra至Re如权利要求1所定义，其适用于治疗以细胞增殖过度或异常为特征的疾病，其用于制备具有上述药物组合物的用途 性质及其制备方法。

公开(公告)号：US20080161297A1

公开(公告)日：2008-07-03

申请号：US11856740

申请日：2007-09-18

Applicant: Todd Bosanac ,  John David Ginn ,  Eugene Richard Hickey ,  Thomas Martin Kirrane ,  Weimin Liu ,  Anthony S. Prokopowicz ,  Sabine K. Schlyer ,  Cheng-Kon Shih ,  Roger John Snow ,  Michael Robert Turner ,  Frank Wu ,  Erick Richard Young

Inventor： Todd Bosanac ,  John David Ginn ,  Eugene Richard Hickey ,  Thomas Martin Kirrane ,  Weimin Liu ,  Anthony S. Prokopowicz ,  Sabine K. Schlyer ,  Cheng-Kon Shih ,  Roger John Snow ,  Michael Robert Turner ,  Frank Wu ,  Erick Richard Young

IPC: A61K31/4725 ,  A61P9/00 ,  A61P13/00 ,  A61P15/10 ,  A61P27/06 ,  A61P11/06 ,  A61K31/517 ,  A61K31/5377 ,  A61K31/496 ,  C07D239/88 ,  C07D217/24 ,  C07D401/02 ,  C07D417/02 ,  A61K31/541 ,  A61K31/472

CPC classification number: A61K31/472 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/517 ,  A61K31/5377 ,  A61K31/541 ,  C07D217/24 ,  C07D239/88 ,  C07D239/90 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D487/08

Abstract: Disclosed are novel substituted 2H-isoquinolin-1-one and 3H-quinazolin-4-one derivatives useful as inhibitors of Rho kinase and for treating a variety of diseases and disorders that are mediated or sustained through the activity of Rho kinase, including cardiovascular diseases, pharmaceutical compositions comprising such compounds, methods for using such compounds and processes for making such compounds.

Abstract translation: 公开了用作Rho激酶抑制剂的新型取代的2H-异喹啉-1-酮和3H-喹唑啉-4-酮衍生物，并用于治疗通过Rho激酶（包括心血管疾病）的活性介导或维持的多种疾病和病症 包含这些化合物的药物组合物，使用这些化合物的方法和制备这些化合物的方法。

公开(公告)号：US08318723B2

公开(公告)日：2012-11-27

申请号：US12377283

申请日：2007-08-15

Applicant: Wang Mao ,  Tina Marie Morwick ,  Anthony S. Prokopowicz, III

Inventor： Wang Mao ,  Tina Marie Morwick ,  Anthony S. Prokopowicz, III

IPC: A61K31/55 ,  A61K31/4965

CPC classification number: C07D401/10 ,  C07D213/74 ,  C07D241/20 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D413/04

Abstract: The invention provides compounds according to formula (I) their use and methods for preparation wherein A, X, Y, R1, R2 and R3 are defined herein. The compounds of the invention inhibit specific serine/threonine kinases involved in inflammatory processes and aberrant cell proliferation, and are thus useful for treating associated diseases and pathological conditions such as Pim kinase-mediated diseases and pathological conditions involving inflammation, including Chron's disease, inflammatory bowel disease, rheumatoid arthritis, and chronic inflammatory disease, or aberrant cell proliferation including various cancers.

Abstract translation: 本发明提供式（I）化合物的用途和制备方法，其中A，X，Y，R 1，R 2和R 3在本文中定义。 本发明的化合物抑制参与炎症过程和异常细胞增殖的特异性丝氨酸/苏氨酸激酶，因此可用于治疗相关疾病和病理状况，例如Pim激酶介导的疾病和涉及炎症的病理状况，包括Chron氏病，炎性肠 疾病，类风湿性关节炎和慢性炎症性疾病，或包括各种癌症在内的异常细胞增殖。

公开(公告)号：US20100280028A1

公开(公告)日：2010-11-04

申请号：US12768268

申请日：2010-04-27

Applicant: Jennifer A. KOWALSKI ,  Daniel Richard MARSHALL ,  Anthony S. PROKOPOWICZ, III ,  Sabine SCHLYER ,  Robert SIBLEY ,  Ronald John SORCEK ,  Di WU ,  Frank WU ,  Erick Richard Roush YOUNG

Inventor： Jennifer A. KOWALSKI ,  Daniel Richard MARSHALL ,  Anthony S. PROKOPOWICZ, III ,  Sabine SCHLYER ,  Robert SIBLEY ,  Ronald John SORCEK ,  Di WU ,  Frank WU ,  Erick Richard Roush YOUNG

IPC: A61K31/5377 ,  C07D403/14 ,  A61K31/506 ,  C07D413/14 ,  A61K31/497 ,  C07D241/04 ,  A61K31/4965 ,  C07D401/12 ,  A61P29/00 ,  A61P9/00 ,  A61P37/00

CPC classification number: C07D471/04 ,  C07D209/48 ,  C07D213/26 ,  C07D213/56 ,  C07D213/65 ,  C07D213/74 ,  C07D217/00 ,  C07D231/10 ,  C07D233/90 ,  C07D235/04 ,  C07D239/34 ,  C07D239/42 ,  C07D277/30 ,  C07D295/185 ,  C07D307/68 ,  C07D317/68 ,  C07D319/18 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D413/12 ,  C07D417/12 ,  C07D491/08

Abstract: The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R1 to R5, A, B, D and X are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

Abstract translation: 本发明涉及式（I）化合物及其药学上可接受的盐，其中R 1至R 5，A，B，D和X如本文所定义。 本发明还涉及包含这些化合物的药物组合物，使用这些化合物治疗各种疾病和病症的方法，制备这些化合物的方法和可用于这些方法的中间体。

公开(公告)号：US07709480B2

公开(公告)日：2010-05-04

申请号：US11313380

申请日：2005-12-21

Applicant: Georg Dahmann ,  Frank Himmelsbach ,  Bernd Krist ,  Martin Lenter ,  Alexander Pautsch ,  Gisela Schapp ,  Martin Steegmaier ,  Helmut Wittneben ,  Anthony S. Prokopowicz ,  Walter Spevak ,  Andreas Schoop ,  Steffen Steurer

Inventor： Georg Dahmann ,  Frank Himmelsbach ,  Bernd Krist ,  Martin Lenter ,  Alexander Pautsch ,  Gisela Schapp ,  Martin Steegmaier ,  Helmut Wittneben ,  Anthony S. Prokopowicz ,  Walter Spevak ,  Andreas Schoop ,  Steffen Steurer

IPC: C07D417/00 ,  C07D239/48 ,  A61K31/506

CPC classification number: C07D239/48 ,  C07D231/12 ,  C07D233/56 ,  C07D239/50 ,  C07D239/80 ,  C07D249/08 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D451/04 ,  C07D451/06 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  C07D487/10

Abstract: The present invention relates to trisubstituted pyrimidines of formula (I) wherein 0Ra to Re are defined as in claim 1, which are suitable for the treatment of illnesses characterized by excessive or abnormal cell proliferation, the use thereof for preparing a pharmaceutical composition with the abovementioned properties, and processes for the preparation thereof.

Abstract translation: 本发明涉及式（I）的三取代嘧啶，其中0Ra至Re如权利要求1所定义，其适用于治疗以细胞增殖过度或异常为特征的疾病，其用于制备具有上述药物组合物的用途 性质及其制备方法。

公开(公告)号：US07550473B2

公开(公告)日：2009-06-23

申请号：US10933635

申请日：2004-09-03

Applicant: Mario G. Cardozo ,  Derek Cogan ,  Charles Lawrence Cywin ,  George Dahmann ,  Darren DiSalvo ,  John David Ginn ,  Anthony S. Prokopowicz, III ,  Denice M. Spero ,  Erick Richard Roush Young

Inventor： Mario G. Cardozo ,  Derek Cogan ,  Charles Lawrence Cywin ,  George Dahmann ,  Darren DiSalvo ,  John David Ginn ,  Anthony S. Prokopowicz, III ,  Denice M. Spero ,  Erick Richard Roush Young

IPC: C07D239/42 ,  A61K31/505

CPC classification number: C07D239/48 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D471/04 ,  H01L51/0089

Abstract: Disclosed are novel compounds of formula (I): wherein R1, R2 and R3 are as defined herein, which are useful as inhibitors of PKC-theta and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC-theta, including immunological disorders and type II diabetes. This invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

Abstract translation: 公开了式（I）的新化合物：其中R 1，R 2和R 3如本文所定义，其可用作PKC-θ的抑制剂，因此可用于治疗通过该活性介导或维持的多种疾病和病症 的PKC-θ，包括免疫学障碍和II型糖尿病。 本发明还涉及包含这些化合物的药物组合物，使用这些化合物治疗各种疾病和病症的方法，制备这些化合物的方法和可用于这些方法的中间体。

公开(公告)号：US07125996B2

公开(公告)日：2006-10-24

申请号：US10955129

申请日：2004-09-30

Applicant: Anthony S. Prokopowicz, III ,  Martha Priscilla Brown ,  Jessi Marie Wildeson ,  Scott Jakes ,  Mark E. Labadia

Inventor： Anthony S. Prokopowicz, III ,  Martha Priscilla Brown ,  Jessi Marie Wildeson ,  Scott Jakes ,  Mark E. Labadia

IPC: C07D239/30 ,  C07D233/96 ,  A61K31/506 ,  C09K11/06

CPC classification number: C07D405/12 ,  C09B11/24 ,  C09B55/003 ,  C12Q1/485 ,  G01N33/533 ,  G01N33/573 ,  G01N33/582 ,  G01N2500/02

Abstract: The invention provides methods relating to a novel screening assay format that can be applied to broad members of the protein kinase gene family. The assay uses a series of labeled, active site probes described herein that can be displaced by an inhibitor agent. The Kd for the inhibitor compound is derived based on the Kd of the probe for the kinase and the dose response of the inhibitor agent. The invention also provides active site probes suitable for use with the screening method.

Abstract translation: 本发明提供了可应用于蛋白激酶基因家族的广泛成员的新型筛选测定形式的方法。 该测定使用本文所述的一系列标记的可被抑制剂代替的活性位点探针。 用于抑制剂化合物的K 基于用于激酶的探针的KⅢ和抑制剂的剂量反应而衍生。 本发明还提供适用于筛选方法的活性位点探针。