公开(公告)号：US08586732B2

公开(公告)日：2013-11-19

申请号：US13538847

申请日：2012-06-29

Applicant: Britton Kenneth Corkey ,  Elfatih Elzein ,  Robert H. Jiang ,  Rao V. Kalla ,  Dmitry Koltun ,  Xiaofen Li ,  Ruben Martinez ,  Eric Q. Parkhill ,  Thao Perry ,  Jeff Zablocki ,  Chandrasekar Venkataramani ,  Michael Graupe ,  Juan Guerrero

Inventor： Britton Kenneth Corkey ,  Elfatih Elzein ,  Robert H. Jiang ,  Rao V. Kalla ,  Dmitry Koltun ,  Xiaofen Li ,  Ruben Martinez ,  Eric Q. Parkhill ,  Thao Perry ,  Jeff Zablocki ,  Chandrasekar Venkataramani ,  Michael Graupe ,  Juan Guerrero

IPC: A61K31/00 ,  C07D267/02

CPC classification number: C07D413/06 ,  A61K31/5513 ,  A61K31/553 ,  C07B59/002 ,  C07B2200/05 ,  C07D243/14 ,  C07D243/24 ,  C07D267/08 ,  C07D267/14 ,  C07D291/08 ,  C07D403/06 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D419/06 ,  C07D471/04 ,  C07D487/04 ,  C07D498/04

Abstract: The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I: wherein Z1, Z2, Z3, Z4, X, Y, R2, R3 and R4 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.

公开(公告)号：US20130012521A1

公开(公告)日：2013-01-10

申请号：US13618841

申请日：2012-09-14

Applicant: Britton Corkey ,  Michael Graupe ,  Keith Koch ,  Lawrence S. Melvin, JR. ,  Gregory Notte

Inventor： Britton Corkey ,  Michael Graupe ,  Keith Koch ,  Lawrence S. Melvin, JR. ,  Gregory Notte

IPC: A61K31/4439 ,  C07D471/04 ,  A61K31/444 ,  A61K31/4709 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/506 ,  A61P9/00 ,  A61P3/10 ,  A61P13/12 ,  A61P11/00 ,  A61P1/16 ,  A61P25/28 ,  A61P29/00 ,  C07D401/14

CPC classification number: A61K31/444 ,  A61K31/4439 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/497 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/585 ,  A61K45/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048

Abstract: The present invention relates to compounds of Formula (I): wherein X1, X2, X3, X4, X5, X6, X7, X8, R1, R2, R3 are as defined above. The compounds have apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases. The invention also relates to pharmaceutical compositions comprising one or more of the compounds of Formula (I), and to methods of preparing the compounds of Formula (I).

Abstract translation: 本发明涉及式（I）的化合物：其中X 1，X 2，X 3，X 4，X 5，X 6，X 7，X 8，R 1，R 2，R 3如上所定义。 该化合物具有凋亡信号调节激酶（ASK1）抑制活性，因此可用于治疗ASK1介导的病症，包括自身免疫疾病，炎性疾病，心血管疾病和神经变性疾病。 本发明还涉及包含一种或多种式（I）化合物的药物组合物和制备式（I）化合物的方法。

公开(公告)号：US08338593B2

公开(公告)日：2012-12-25

申请号：US12303214

申请日：2007-07-06

Applicant: Lee S. Chong ,  Manoj C. Desai ,  Brian Gallagher ,  Michael Graupe ,  Randall L. Halcomb ,  Hong Yang ,  Jennifer R. Zhang

Inventor： Lee S. Chong ,  Manoj C. Desai ,  Brian Gallagher ,  Michael Graupe ,  Randall L. Halcomb ,  Hong Yang ,  Jennifer R. Zhang

IPC: C07F9/6561 ,  C07D473/16 ,  A61K31/675 ,  A61P31/20 ,  C07D473/40

CPC classification number: C07F9/65616

Abstract: The present application provides for a compound of Formula (I) or (II): or a pharmaceutically acceptable salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods that include the administration of such compounds with at least one additional active agent.

Abstract translation: 本申请提供式（I）或（II）的化合物或其药学上可接受的盐，溶剂合物和/或酯，含有这些化合物的组合物，包括施用这些化合物的治疗方法和治疗方法， 包括给予这些化合物与至少一种另外的活性剂。

公开(公告)号：US07968544B2

公开(公告)日：2011-06-28

申请号：US12215598

申请日：2008-06-26

Applicant: Michael Graupe ,  Randall L. Halcomb

Inventor： Michael Graupe ,  Randall L. Halcomb

IPC: C07D473/18 ,  A61K31/522 ,  A61P31/20 ,  A61K31/14

CPC classification number: C07D473/18 ,  A61K31/522 ,  A61K31/5377 ,  A61K31/55 ,  A61K31/551 ,  A61K45/06

Abstract: The present application includes a compound of Formula I or II: or a pharmaceutically acceptable-salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods that include the administration of such compounds with at least one additional active agent.

Abstract translation: 本申请包括式I或II化合物或其药学上可接受的盐，溶剂合物和/或酯，含有这些化合物的组合物，包括施用这些化合物的治疗方法和包括施用 这种化合物与至少一种另外的活性剂。

公开(公告)号：US20110135594A1

公开(公告)日：2011-06-09

申请号：US12997487

申请日：2009-07-14

Applicant: Michael Graupe ,  Chandrasekar Venkataramani

Inventor： Michael Graupe ,  Chandrasekar Venkataramani

IPC: A61K31/404 ,  C07D209/34 ,  C07D413/12 ,  C07D417/10 ,  C07D403/10 ,  C07D405/10 ,  C07D513/04 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  A61K31/5377 ,  A61K31/427 ,  A61K31/4178 ,  A61K31/496 ,  A61K31/429 ,  A61K31/675 ,  A61K33/24 ,  A61K31/519 ,  A61K31/52 ,  A61K31/513 ,  A61K31/7068 ,  A61K31/704 ,  A61K38/12 ,  A61K38/50 ,  A61K39/395 ,  A61K38/19 ,  A61P35/00 ,  A61P3/00 ,  A61P37/06 ,  A61P3/10 ,  A61P25/00 ,  A61P25/28 ,  A61P11/00 ,  A61P19/04 ,  A61P13/12 ,  A61P35/02

CPC classification number: C07D209/34 ,  C07D407/10 ,  C07D409/12 ,  C07D409/14 ,  C07D413/10 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D487/04 ,  C07D513/04

Abstract: A compound of general Formula (I) having histone deacetylase (HDAC) and/or CDK inhibitory activity, a pharmaceutical composition comprising the compound, and a method useful to treat diseases using the compound. (Formula should be inserted here) Formula (I)

Abstract translation: 具有组蛋白脱乙酰酶（HDAC）和/或CDK抑制活性的通式（I）的化合物，包含该化合物的药物组合物和可用于使用该化合物治疗疾病的方法。 （公式应在此插入）公式（I）

公开(公告)号：US20090170909A1

公开(公告)日：2009-07-02

申请号：US12337596

申请日：2008-12-17

Applicant: Michael Graupe ,  John O. Link ,  Michael G. Roepel

Inventor： Michael Graupe ,  John O. Link ,  Michael G. Roepel

IPC: A61K31/44 ,  A61K31/164 ,  A61P37/00 ,  A61P29/00

CPC classification number: C07C317/48 ,  C07C2601/02 ,  C07D213/32

Abstract: The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.

Abstract translation: 本发明涉及半胱氨酸蛋白酶，特别是组织蛋白酶B，K，L，F和S的抑制剂的化合物，因此可用于治疗由这些蛋白酶介导的疾病。 本发明涉及包含这些化合物的药物组合物及其制备方法。

公开(公告)号：US20070054864A1

公开(公告)日：2007-03-08

申请号：US11478337

申请日：2006-06-28

Applicant: Michael Graupe ,  John Link ,  Chandrasekar Venkataramani

Inventor： Michael Graupe ,  John Link ,  Chandrasekar Venkataramani

IPC: A61K38/05 ,  C07K5/06

CPC classification number: A61K38/05 ,  C07K5/06034

Abstract: The present invention is directed to compounds that are antiviral agents. Specifically the compounds of the present invention inhibit replication of HCV and are therefore useful in treating hepatitis C infections. The present invention is also directed to pharmaceutical compositions comprising these compounds and processes for preparing them.

Abstract translation: 本发明涉及作为抗病毒剂的化合物。 具体地说，本发明的化合物抑制HCV的复制，因此可用于治疗丙型肝炎感染。 本发明还涉及包含这些化合物的药物组合物及其制备方法。

公开(公告)号：US07101880B2

公开(公告)日：2006-09-05

申请号：US10603437

申请日：2003-06-24

Applicant: Michael Graupe ,  John O. Link

Inventor： Michael Graupe ,  John O. Link

IPC: A61K31/535 ,  C07D413/00

CPC classification number: C07D263/56 ,  A61K38/00 ,  C07D413/12 ,  C07D417/12

Abstract: The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.

Abstract translation: 本发明涉及半胱氨酸蛋白酶，特别是组织蛋白酶B，K，L，F和S的抑制剂的化合物，因此可用于治疗由这些蛋白酶介导的疾病。 本发明涉及包含这些化合物的药物组合物及其制备方法。

公开(公告)号：US20140135317A1

公开(公告)日：2014-05-15

申请号：US14038646

申请日：2013-09-26

Applicant: Britton Kenneth Corkey ,  Elfatih Elzein ,  Robert H. Jiang ,  Rao V. Kalla ,  Dmitry Koltun ,  Xiaofen Li ,  Rubin Martinez ,  Eric Q. Parkhill ,  Thao Perry ,  Jeff Zablocki ,  Chandrasekar Venkataramani ,  Michael Graupe ,  Juan Guerrero

Inventor： Britton Kenneth Corkey ,  Elfatih Elzein ,  Robert H. Jiang ,  Rao V. Kalla ,  Dmitry Koltun ,  Xiaofen Li ,  Rubin Martinez ,  Eric Q. Parkhill ,  Thao Perry ,  Jeff Zablocki ,  Chandrasekar Venkataramani ,  Michael Graupe ,  Juan Guerrero

IPC: C07D243/14 ,  C07D403/06

CPC classification number: C07D413/06 ,  A61K31/5513 ,  A61K31/553 ,  C07B59/002 ,  C07B2200/05 ,  C07D243/14 ,  C07D243/24 ,  C07D267/08 ,  C07D267/14 ,  C07D291/08 ,  C07D403/06 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D419/06 ,  C07D471/04 ,  C07D487/04 ,  C07D498/04

Abstract: The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I: wherein Z1, Z2, Z3, Z4, X, Y, R2, R3 and R4 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.

Abstract translation: 本公开涉及作为钠通道抑制剂的化合物及其用于治疗各种疾病状态（包括心血管疾病和糖尿病）的用途。 在具体实施方案中，化合物的结构由式I给出：其中Z 1，Z 2，Z 3，Z 4，X，Y，R 2，R 3和R 4如本文所述，用于制备和使用该化合物的方法， 含有该组合物的药物组合物。

公开(公告)号：US08552196B2

公开(公告)日：2013-10-08

申请号：US13615259

申请日：2012-09-13

Applicant: Britton Corkey ,  Michael Graupe ,  Keith Koch ,  Lawrence S. Melvin, Jr. ,  Gregory Notte

Inventor： Britton Corkey ,  Michael Graupe ,  Keith Koch ,  Lawrence S. Melvin, Jr. ,  Gregory Notte

IPC: A61K31/4439 ,  A61K31/444 ,  A61K31/496 ,  A61K31/506 ,  A61K31/5377 ,  A61P1/16 ,  A61P25/28 ,  A61P29/00 ,  A61P37/06 ,  A61P13/12 ,  A61P9/00 ,  A61P3/10 ,  A61P11/00

CPC classification number: A61K31/444 ,  A61K31/4439 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/497 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/585 ,  A61K45/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048

Abstract: The present invention relates to compounds of Formula (I): wherein X1, X2, X3, X4, X5, X6, X7, X8, R1, R2, R3 are defined above. The compounds have apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases. The invention also relates to pharmaceutical compositions comprising one or more of the compounds of Formula (I), and to methods of preparing the compounds of Formula (I).

Abstract translation: 本发明涉及式（I）的化合物：其中X 1，X 2，X 3，X 4，X 5，X 6，X 7，X 8，R 1，R 2，R 3如上所定义。 该化合物具有凋亡信号调节激酶（“ASK1”）抑制活性，因此可用于治疗ASK1介导的病症，包括自身免疫性疾病，炎性疾病，心血管疾病和神经变性疾病。 本发明还涉及包含一种或多种式（I）化合物的药物组合物和制备式（I）化合物的方法。