公开(公告)号：US07566708B2

公开(公告)日：2009-07-28

申请号：US11509115

申请日：2006-08-23

Applicant: Nidhi Arora ,  Roland Joseph Billedeau ,  Nolan James Dewdney ,  Tobias Gabriel ,  David Michael Goldstein ,  Counde O'Yang ,  Michael Soth ,  Teresa Alejandra Trejo-Martin

Inventor： Nidhi Arora ,  Roland Joseph Billedeau ,  Nolan James Dewdney ,  Tobias Gabriel ,  David Michael Goldstein ,  Counde O'Yang ,  Michael Soth ,  Teresa Alejandra Trejo-Martin

IPC: C07D487/04 ,  A61K31/519 ,  A61P31/18 ,  A61P31/22 ,  A61P37/08 ,  A61P31/16

CPC classification number: C07D471/04 ,  C07D487/04

Abstract: Compounds effective as p38 MAP kinase inhibitors, methods of making the compounds, and methods of using the compounds for treatment of p38 MAP kinase-mediated diseases.

Abstract translation: 作为p38 MAP激酶抑制剂有效的化合物，制备化合物的方法，以及使用该化合物治疗p38 MAP激酶介导的疾病的方法。

公开(公告)号：US07563799B2

公开(公告)日：2009-07-21

申请号：US11509422

申请日：2006-08-23

Applicant: Roland Joseph Billedeau ,  Nolan James Dewdney ,  Tobias Gabriel

Inventor： Roland Joseph Billedeau ,  Nolan James Dewdney ,  Tobias Gabriel

IPC: C07D487/04 ,  A61K31/519 ,  A61P11/04 ,  A61P19/02

CPC classification number: C07D487/04

Abstract: Compounds of the formula Ia or Ib: wherein X and Y are N or one of X and Y is N and the other is CRg, and A, D, E, G, W, R1, R2, R3, R4 and R5 are as defined herein. Also disclosed are methods of making the subject compounds and methods of using the compounds for treatment of p38 MAP kinase-mediated diseases.

Abstract translation: 式Ia或Ib化合物：其中X和Y为N或X和Y中的一个为N，另一个为CRg，A，D，E，G，W，R 1，R 2，R 3，R 4和R 5为 本文定义。 还公开了制备本发明化合物的方法和使用该化合物治疗p38MAP激酶介导的疾病的方法。

公开(公告)号：US20090105209A1

公开(公告)日：2009-04-23

申请号：US12288730

申请日：2008-10-23

Applicant: Nolan James Dewdney ,  Rama K. Kondru ,  Yan Lou ,  Michael Soth ,  Tobias Gabriel

Inventor： Nolan James Dewdney ,  Rama K. Kondru ,  Yan Lou ,  Michael Soth ,  Tobias Gabriel

IPC: A61K31/5377 ,  C07D403/14 ,  C07D417/14 ,  A61K31/501

CPC classification number: C07D213/63 ,  C07D401/12 ,  C07D401/14 ,  C07D403/14 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14

Abstract: This application discloses pyridine and pyrimidine compounds according to formula I wherein R1, R2, R3, R4, R5, X1 and A are as described herein which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of formula I and at least one carrier, diluent or excipient.

Abstract translation: 本申请公开了根据式I的吡啶和嘧啶化合物，其中R 1，R 2，R 3，R 4，R 5，X 1和A如本文所述抑制Btk。 本文公开的化合物可用于调节Btk的活性并治疗与过量Btk活性相关的疾病。 该化合物还可用于治疗与异常B细胞增殖相关的炎症和自身免疫疾病，例如类风湿性关节炎。 还公开了含有式I化合物和至少一种载体，稀释剂或赋形剂的组合物。

公开(公告)号：US07495015B2

公开(公告)日：2009-02-24

申请号：US11065979

申请日：2005-02-25

Applicant: Nidhi Arora ,  Tobias Gabriel ,  David Michael Goldstein ,  Teresa Alejandra Trejo-Martin

Inventor： Nidhi Arora ,  Tobias Gabriel ,  David Michael Goldstein ,  Teresa Alejandra Trejo-Martin

IPC: A61K31/4439

CPC classification number: C07D231/56

Abstract: Compounds of the formula I: or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein m, k, B, R1, R2 and R3 are those defined herein, and compositions comprising the same. Also provided are methods for preparing compounds of formula I and using the same in treating p38 mediated disorders in a patient.

Abstract translation: 式I化合物或其药学上可接受的盐，溶剂合物或前药，其中m，k，B，R 1，R 2和R 3是本文定义的那些，以及包含其的组合物。 还提供了制备式I化合物的方法，并将其用于治疗患者中p38介导的病症。

公开(公告)号：US07435731B2

公开(公告)日：2008-10-14

申请号：US11067336

申请日：2005-02-25

Applicant: Nidhi Arora ,  Roland Joseph Billedeau ,  Nolan James Dewdney ,  Tobias Gabriel ,  David Michael Goldstein ,  Counde O'Yang ,  Michael Soth

Inventor： Nidhi Arora ,  Roland Joseph Billedeau ,  Nolan James Dewdney ,  Tobias Gabriel ,  David Michael Goldstein ,  Counde O'Yang ,  Michael Soth

IPC: C07D487/04 ,  C07D413/04 ,  C07D413/12 ,  A61K31/519 ,  A61K31/541 ,  A61K31/5355 ,  C07D471/04 ,  A61K31/437 ,  A61P19/02 ,  A61P11/16

CPC classification number: C07D487/04 ,  C07D471/04

Abstract: Compounds of the formula Ia or Ib: wherein A, B, X, Y, Z, W, k, R1, R2, R3, R4 and R5 are those defined herein, and compositions comprising the same. The present invention also provides methods for preparing compounds of formula I and using the same in treating p38 mediated disorders in a subject.

Abstract translation: 式Ia或Ib化合物：其中A，B，X，Y，Z，W，k，R 1，R 2，R 3， SUP，R 4和R 5是本文定义的那些，以及包含它们的组合物。 本发明还提供了制备式I化合物的方法，并且使用它们来治疗受试者中p38介导的病症。

公开(公告)号：US20050215595A1

公开(公告)日：2005-09-29

申请号：US11065979

申请日：2005-02-25

Applicant: Nidhi Arora ,  Tobias Gabriel ,  David Goldstein ,  Teresa Trejo-Martin

Inventor： Nidhi Arora ,  Tobias Gabriel ,  David Goldstein ,  Teresa Trejo-Martin

IPC: C07D231/56 ,  A61K31/4439 ,  A61K31/416 ,  C07D43/02

CPC classification number: C07D231/56

Abstract: Compounds of the formula I: or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein m, k, B, R1, R2 and R3 are those defined herein, and compositions comprising the same. Also provided are methods for preparing compounds of formula I and using the same in treating p38 mediated disorders in a patient.

Abstract translation: 式I化合物或其药学上可接受的盐，溶剂化物或前体药物，其中m，k，B，R 1，R 2和R 3， SUP>是本文定义的那些，以及包含它们的组合物。 还提供了制备式I化合物的方法，并将其用于治疗患者中p38介导的病症。

公开(公告)号：US06747053B2

公开(公告)日：2004-06-08

申请号：US10308963

申请日：2002-12-03

Applicant: Tobias Gabriel ,  Nancy Elisabeth Krauss ,  Taraneh Mirzadegan ,  Wylie Solang Palmer ,  David Bernard Smith

Inventor： Tobias Gabriel ,  Nancy Elisabeth Krauss ,  Taraneh Mirzadegan ,  Wylie Solang Palmer ,  David Bernard Smith

IPC: A61K31404

CPC classification number: C07D405/12 ,  C07D209/08 ,  C07D209/42 ,  C07D213/81 ,  C07D215/40 ,  C07D215/48 ,  C07D215/54 ,  C07D215/60 ,  C07D217/02 ,  C07D231/38 ,  C07D231/56 ,  C07D241/44 ,  C07D277/62 ,  C07D401/12 ,  C07D409/12 ,  C07D471/04 ,  C07D513/04

Abstract: The present invention relates to compound of formula (I) wherein R1, R2, R3, R4, R5 and n are as defined in the description and claims and pharmaceutically acceptable salts and/or pharmaceutically acceptable esters thereof. The compounds are useful for the treatment of diseases which are associated with cysteine proteases such as osteoporosis, osteoarthritis, rheumatoid arthritis, tumor metastasis, glomerulonephritis, atherosclerosis, myocardial infarction, angina pectoris, instable angina pectoris, stroke, plaque rupture, transient ischemic attacks, amaurosis fugax, peripheral arterial occlusive disease, restenosis after angioplasty and stent placement, abdominal aortic aneurysm formation, inflammation, autoimmune disease, malaria, ocular fundus tissue cytopathy and respiratory disease.

Abstract translation: 本发明涉及其中R 1，R 2，R 3，R 4，R 5和n如说明书和权利要求中所定义的式（I）化合物及其药学上可接受的盐 和/或其药学上可接受的酯。 该化合物可用于治疗与半胱氨酸蛋白酶如骨质疏松症，骨关节炎，类风湿性关节炎，肿瘤转移，肾小球性肾炎，动脉粥样硬化，心肌梗死，心绞痛，不稳定性心绞痛，中风，斑块破裂，短暂性脑缺血发作， 外周动脉闭塞性疾病，血管成形术和支架置入后再狭窄，腹主动脉瘤形成，炎症，自身免疫性疾病，疟疾，眼底组织细胞病变和呼吸系统疾病。

公开(公告)号：US06531612B2

公开(公告)日：2003-03-11

申请号：US09745675

申请日：2000-12-21

Applicant: Tobias Gabriel ,  Michael Pech ,  Sabine Wallbaum

Inventor： Tobias Gabriel ,  Michael Pech ,  Sabine Wallbaum

IPC: C07D20716

CPC classification number: C07D403/06 ,  C07D207/16 ,  C07D207/48 ,  C07D209/52 ,  C07D277/06 ,  C07D405/12 ,  C07D405/14

Abstract: Compounds of the formula: wherein R1 to R7 and Y are as defined in the specification, and pharmaceutically acceptable salts and/or pharmaceutically acceptable esters thereof, are useful for treating diseases associated with cystein proteases, such as osteoporosis, osteoarthritis, rheumatoid arthritis, tumor metastasis, glomerulonephritis, atherosclerosis, myocardial infarction, angina pectoris, instable angina pectoris, stroke, plaque rupture, transient ischemic attacks, amaurosis fugax, peripheral arterial occlusive disease, restenosis after angioplasty and stent placement, abdominal aortic aneurysm formation, inflammation, autoimmune disease, malaria, ocular fundus tissue cytopathy and respiratory disease.

Abstract translation: 下式的化合物：其中R 1至R 7和Y如说明书中所定义，及其药学上可接受的盐和/或其药学上可接受的酯可用于治疗与半胱氨酸蛋白酶相关的疾病，例如骨质疏松症，骨关节炎，类风湿性关节炎，肿瘤 转移，肾小球性肾炎，动脉粥样硬化，心肌梗塞，心绞痛，不稳定性心绞痛，中风，斑块破裂，短暂性脑缺血发作，黑素瘤假体，外周动脉闭塞性疾病，血管成形术后再狭窄和支架置入，腹主动脉瘤形成，炎症，自身免疫性疾病， 疟疾，眼底组织细胞病变和呼吸系统疾病。

公开(公告)号：US07608603B2

公开(公告)日：2009-10-27

申请号：US11509121

申请日：2006-08-23

Applicant: Nolan James Dewdney ,  Tobias Gabriel ,  Kristen Lynn McCaleb

Inventor： Nolan James Dewdney ,  Tobias Gabriel ,  Kristen Lynn McCaleb

IPC: C07F9/09 ,  C07D487/04 ,  A61K31/519 ,  A61K31/661 ,  A61P11/16 ,  A61P19/02

CPC classification number: C07D487/04

Abstract: Compounds of formula Ia, Ib, Ic, Id, Ie, If, Ig or Ih: wherein X and Y are nitrogen or one of X and Y is nitrogen and the other is CRg, and W, D, E, R4, R5, R6 and Rg are as defined herein. Also disclosed are methods of making the subject compounds and methods of using the compounds in the treatment of p38 MAP kinase-mediated diseases.

Abstract translation: 式Ia，Ib，Ic，Id，Ie，If，Ig或Ih的化合物：其中X和Y是氮或X和Y中的一个是氮，另一个是CR 1，W，D，E，R 4，R 5， R6和Rg如本文所定义。 还公开了制备本发明化合物的方法和使用该化合物治疗p38 MAP激酶介导的疾病的方法。

公开(公告)号：US20080132528A1

公开(公告)日：2008-06-05

申请号：US11983313

申请日：2007-11-08

Applicant: Tobias Gabriel ,  Joel McIntosh ,  Kin-Chun Thomas Luk

Inventor： Tobias Gabriel ,  Joel McIntosh ,  Kin-Chun Thomas Luk

IPC: A61K31/519 ,  A61P35/00 ,  A61P11/00 ,  A61P19/02 ,  A61P1/00 ,  A61P27/00 ,  C07D471/04

CPC classification number: C07D471/04

Abstract: Compounds of formula I: wherein R1, R2, R3 and R4 are as defined herein. Also disclosed are methods of making the compounds, pharmaceutical compositions, methods of using the compounds for treatment of p38 MAP kinase-mediated diseases, and methods of using the compounds for treatment of Raf kinase-mediated diseases.

Abstract translation: 式I化合物：其中R 1，R 2，R 3和R 4如本文所定义。 还公开了制备化合物，药物组合物，使用该化合物治疗p38 MAP激酶介导的疾病的方法的方法，以及使用该化合物治疗Raf激酶介导的疾病的方法。