公开(公告)号：US20090047246A1

公开(公告)日：2009-02-19

申请号：US12029399

申请日：2008-02-11

Applicant: Leonid Beigelman ,  Brad Buckman ,  Vladimir Serebryany ,  Guangyi Wang ,  Jasenka Matulic-Adamic ,  Antitsa Dimitrova Stoycheva ,  Steven W. Andrews ,  Shawn Maurice Misialek ,  P.T. Ravi Rajagopalan ,  Andrew M. Fryer ,  Indrani Gunawardana ,  Julia Haas ,  Lily Huang ,  Machender R. Madduru ,  Gan Zhang ,  Karl Kossen ,  Scott D. Seiwert ,  Lawrence M. Blatt

Inventor： Leonid Beigelman ,  Brad Buckman ,  Vladimir Serebryany ,  Guangyi Wang ,  Jasenka Matulic-Adamic ,  Antitsa Dimitrova Stoycheva ,  Steven W. Andrews ,  Shawn Maurice Misialek ,  P.T. Ravi Rajagopalan ,  Andrew M. Fryer ,  Indrani Gunawardana ,  Julia Haas ,  Lily Huang ,  Machender R. Madduru ,  Gan Zhang ,  Karl Kossen ,  Scott D. Seiwert ,  Lawrence M. Blatt

IPC: A61K38/21 ,  C07D409/06 ,  A61K31/405 ,  A61K31/506 ,  C07D403/08 ,  A61K31/404 ,  C07D209/20 ,  A61K31/675 ,  C07F9/572 ,  A61K31/437 ,  C07D471/02 ,  C12N9/99 ,  A61K31/44 ,  A61K39/395 ,  A61K31/427 ,  C12N9/50 ,  C12N9/00 ,  C12Q1/68 ,  G01N33/53

CPC classification number: C07F9/65583 ,  C07D209/18 ,  C07D209/30 ,  C07D209/32 ,  C07D307/79 ,  C07D333/60 ,  C07D401/10 ,  C07D403/06 ,  C07D403/10 ,  C07D403/12 ,  C07D407/06 ,  C07D409/04 ,  C07D409/06 ,  C07D409/12 ,  C07D409/14 ,  C07D413/06 ,  C07D413/10 ,  C07D417/06 ,  C07D487/04 ,  C07F9/5728 ,  C12Q1/707 ,  G01N2333/186 ,  G01N2333/914

Abstract: The embodiments provide compounds of the general Formula I, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.

Abstract translation: 实施方案提供了通式I的化合物，以及包含主题化合物的组合物，包括药物组合物。 实施方案还提供治疗方法，包括治疗丙型肝炎病毒感染的方法，所述方法通常涉及向有需要的个体施用有效量的主题化合物或组合物。

公开(公告)号：US08975235B2

公开(公告)日：2015-03-10

申请号：US13585716

申请日：2012-08-14

Applicant: Brad O. Buckman ,  John B. Nicholas ,  Kumaraswamy Emayan ,  Scott D. Seiwert

Inventor： Brad O. Buckman ,  John B. Nicholas ,  Kumaraswamy Emayan ,  Scott D. Seiwert

IPC: C07D495/04 ,  C07D307/66 ,  C07D213/75 ,  C07D413/10 ,  C07D417/12 ,  C07D231/40 ,  C07D401/10 ,  C07D405/12 ,  C07D413/04 ,  C07D249/06 ,  C07D257/06 ,  C07D401/04 ,  A61K31/381 ,  A61K31/426 ,  C07D333/20 ,  A61K31/4192 ,  A61K31/4427 ,  A61K31/415 ,  C07D275/03 ,  C07D261/14 ,  A61K31/4155 ,  C07D471/04 ,  C07H15/26 ,  C07D491/04 ,  A61K31/425 ,  A61K31/421 ,  C07D491/048 ,  C07D277/46 ,  C07D263/48 ,  C07D207/34 ,  A61K31/42

CPC classification number: C07D495/04 ,  A61K31/381 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/4192 ,  A61K31/42 ,  A61K31/421 ,  A61K31/425 ,  A61K31/426 ,  A61K31/4427 ,  C07D207/34 ,  C07D213/75 ,  C07D231/40 ,  C07D249/06 ,  C07D257/06 ,  C07D261/14 ,  C07D263/48 ,  C07D275/03 ,  C07D277/46 ,  C07D307/66 ,  C07D333/20 ,  C07D401/04 ,  C07D401/10 ,  C07D405/12 ,  C07D413/04 ,  C07D413/10 ,  C07D417/12 ,  C07D471/04 ,  C07D491/04 ,  C07D491/048 ,  C07H15/26

Abstract: Compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat, prevent or diagnose diseases, disorders, or conditions associated with one or more of the lysophosphatidic acid receptors are provided.

Abstract translation: 提供了化合物，制备这种化合物的方法，药物组合物和包含这些化合物的药物，以及使用这些化合物治疗，预防或诊断与一种或多种溶血磷脂酸受体相关的疾病，病症或病症的方法。

公开(公告)号：US20130072449A1

公开(公告)日：2013-03-21

申请号：US13585716

申请日：2012-08-14

Applicant: Brad O. Buckman ,  John B. Nicholas ,  Kumaraswamy Emayan ,  Scott D. Seiwert

Inventor： Brad O. Buckman ,  John B. Nicholas ,  Kumaraswamy Emayan ,  Scott D. Seiwert

IPC: A61K31/7042 ,  C07D495/04 ,  C07D261/14 ,  C07D417/12 ,  C07D413/10 ,  C07D491/048 ,  C07H15/26 ,  C07D213/75 ,  A61K31/519 ,  C07D487/04 ,  A61K31/5025 ,  A61K31/53

CPC classification number: C07D495/04 ,  A61K31/381 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/4192 ,  A61K31/42 ,  A61K31/421 ,  A61K31/425 ,  A61K31/426 ,  A61K31/4427 ,  C07D207/34 ,  C07D213/75 ,  C07D231/40 ,  C07D249/06 ,  C07D257/06 ,  C07D261/14 ,  C07D263/48 ,  C07D275/03 ,  C07D277/46 ,  C07D307/66 ,  C07D333/20 ,  C07D401/04 ,  C07D401/10 ,  C07D405/12 ,  C07D413/04 ,  C07D413/10 ,  C07D417/12 ,  C07D471/04 ,  C07D491/04 ,  C07D491/048 ,  C07H15/26

Abstract: Compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat, prevent or diagnose diseases, disorders, or conditions associated with one or more of the lysophosphatidic acid receptors are provided.

Abstract translation: 提供了化合物，制备这种化合物的方法，药物组合物和包含这些化合物的药物，以及使用这些化合物治疗，预防或诊断与一种或多种溶血磷脂酸受体相关的疾病，病症或病症的方法。

公开(公告)号：US08304413B2

公开(公告)日：2012-11-06

申请号：US12477715

申请日：2009-06-03

Applicant: Karl Kossen ,  Scott D. Seiwert ,  Vladimir Serebryany ,  Donald Ruhrmund ,  Leonid Beigelman ,  Luca Francesco Mario Raveglia ,  Stefania Vallese ,  Ivana Bianchi ,  Tao Hu

Inventor： Karl Kossen ,  Scott D. Seiwert ,  Vladimir Serebryany ,  Donald Ruhrmund ,  Leonid Beigelman ,  Luca Francesco Mario Raveglia ,  Stefania Vallese ,  Ivana Bianchi ,  Tao Hu

IPC: A61K31/50 ,  A61K31/497 ,  A61K31/437 ,  A61K31/44

CPC classification number: C07D213/63 ,  C07D213/22 ,  C07D213/64 ,  C07D213/69 ,  C07D213/71 ,  C07D213/85 ,  C07D237/14 ,  C07D239/36 ,  C07D239/54 ,  C07D241/18 ,  C07D251/10 ,  C07D401/04 ,  C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D413/04 ,  C07D413/14 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04

Abstract: Disclosed are compounds and methods for treating inflammatory and fibrotic disorders, including methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of the p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the p38 MAPK by the compound. Also disclosed are derivatives and analogs of pirfenidone, useful for modulating a stress activated protein kinase (SAPK) system.

Abstract translation: 公开了用于治疗炎症和纤维化疾病的化合物和方法，包括用活性化合物调节应激活化蛋白激酶（SAPK）系统的方法，其中活性化合物表现出低的抑制p38MAPK的能力; 并且其中所述接触以对所述化合物抑制p38MAPK的抑制浓度低的SAPK调节浓度进行。 还公开了吡非尼酮的衍生物和类似物，其可用于调节应激活化蛋白激酶（SAPK）系统。

公开(公告)号：US20110312996A1

公开(公告)日：2011-12-22

申请号：US13108211

申请日：2011-05-16

Applicant: Brad Buckman ,  John B. Nicholas ,  Vladimir Serebryany ,  Scott D. Seiwert

Inventor： Brad Buckman ,  John B. Nicholas ,  Vladimir Serebryany ,  Scott D. Seiwert

IPC: A61K31/4709 ,  C07D401/12 ,  C07D233/28 ,  C07D403/12 ,  C07D403/14 ,  C07D417/14 ,  C07D409/14 ,  C07D413/14 ,  C07D405/14 ,  C07D401/14 ,  C07D487/04 ,  C07D471/04 ,  A61K31/4184 ,  A61K31/4178 ,  A61K31/428 ,  A61K31/423 ,  A61P31/14 ,  A61P1/16 ,  C07D403/04

CPC classification number: C07D403/04 ,  A61K31/4025 ,  A61K31/4178 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/428 ,  A61K31/4365 ,  A61K31/437 ,  A61K31/439 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/517 ,  A61K31/519 ,  A61K31/55 ,  A61K31/558 ,  A61K31/5585 ,  C07D207/16 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  C07D513/04

Abstract: The embodiments provide compounds of the general Formulae VI, VII, VIII, IX, X, XI, XII, XIII, XIV, and XV as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.

Abstract translation: 实施方案提供了通式VI，VII，VIII，IX，X，XI，XII，XIII，XIV和XV的化合物以及包含主题化合物的组合物，包括药物组合物。 实施方案还提供治疗方法，包括治疗丙型肝炎病毒感染的方法和治疗肝纤维化的方法，所述方法通常涉及向有需要的个体施用有效量的主题化合物或组合物。

公开(公告)号：US20110034495A1

公开(公告)日：2011-02-10

申请号：US12094230

申请日：2006-11-22

Applicant: Scott D. Seiwert ,  Karl Kossen ,  Vladimir Serebryany

Inventor： Scott D. Seiwert ,  Karl Kossen ,  Vladimir Serebryany

IPC: A61K31/506 ,  C07D471/02 ,  C07D401/14 ,  C07D231/10 ,  C07D401/04 ,  A61K31/4365 ,  A61K31/415 ,  A61K31/4439 ,  A61P29/00 ,  A61P11/00 ,  A61P19/02 ,  A61P17/00 ,  A61P31/00 ,  A61P3/10

CPC classification number: C07D495/04

Abstract: A series of thieno[2,3-b]pyridin-6(7H)-one derivatives, substituted in the 2-position by a carbonyl- or sulfonyl-linked pyrrolidin-1-yl or related moiety, being inhibitors of p38 MAP kinase, are accordingly of use in medicine, for example in the treatment and/or prevention of immune or inflammatory disorders.

Abstract translation: 在2-位被羰基或磺酰基连接的吡咯烷-1-基或相关部分取代的一系列噻吩并[2,3-b]吡啶-6（7H） - 酮衍生物，是p38MAP激酶的抑制剂 因此在药物中使用，例如用于治疗和/或预防免疫或炎症性疾病。

公开(公告)号：US20110008289A1

公开(公告)日：2011-01-13

申请号：US12542561

申请日：2009-08-17

Applicant: LAWRENCE M. BLATT ,  SCOTT D. SEIWERT ,  JIN HONG

Inventor： LAWRENCE M. BLATT ,  SCOTT D. SEIWERT ,  JIN HONG

IPC: A61K38/21 ,  C07K14/52 ,  A61P37/00

CPC classification number: C07K14/555 ,  A61K38/00 ,  C07K14/56 ,  C07K14/565 ,  C07K14/57 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/393

Abstract: The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon receptor polypeptide agonists, containing one or more native or non-native glycosylation sites. The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon receptor polypeptide agonists, containing one or more native or non-native glycosylation sites, as well as erythropoietin and darbepoetin alfa, each of which are linked to a penetrating peptide that facilitates translocation of a substance across a biological barrier as well as pharmaceutical compositions, including oral formulations, of the same. The present invention further provides oral formulations of hyperglycosylated or protease-resistant, hyperglycosylated polypeptide variants, which polypeptide variants lack at least one protease cleavage site found in a parent polypeptide, and thus exhibit increased protease resistance compared to the parent polypeptide, which polypeptide variants further include (1) a carbohydrate moiety covalently linked to at least one non-native glycosylation site not found in the parent protein therapeutic or (2) a carbohydrate moiety covalently linked to at least one native glycosylation site found but not glycosylated in the parent protein therapeutic. The present invention further provides compositions, including oral pharmaceutical compositions, comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides containers, devices, and kits comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides therapeutic methods involving administering an effective amount of an oral pharmaceutical composition comprising a synthetic Type I interferon receptor polypeptide agonist, a hyperglycosylated polypeptide variant, or a hyperglycosylated, protease-resistant polypeptide variant to an individual in need thereof.

公开(公告)号：US20100240704A1

公开(公告)日：2010-09-23

申请号：US12790099

申请日：2010-05-28

Applicant: Lawrence M. Blatt ,  Scott D. Seiwert ,  Leonid Beigelman ,  Ramachandran Radhakrishnan ,  Karl Kossen ,  Vladimir Serebryany

Inventor： Lawrence M. Blatt ,  Scott D. Seiwert ,  Leonid Beigelman ,  Ramachandran Radhakrishnan ,  Karl Kossen ,  Vladimir Serebryany

IPC: A61K31/444 ,  A61K31/4418 ,  C40B30/04 ,  C07D213/22 ,  C07D213/63 ,  C07D211/72 ,  A61P25/28 ,  A61P9/10 ,  A61P31/18 ,  A61P31/12 ,  A61P31/22 ,  A61P37/02

CPC classification number: A61K31/4412 ,  A61K31/44 ,  A61K31/444 ,  A61K31/45 ,  A61K31/4704 ,  A61K31/7052 ,  A61K47/56 ,  A61K47/58 ,  C07D213/16 ,  C07D213/26 ,  C07D213/63 ,  C07D213/64 ,  C07D213/69 ,  C07D215/227 ,  C07H15/26 ,  C07K1/1077 ,  C08F289/00 ,  Y02A50/401 ,  Y02A50/409 ,  Y02A50/411 ,  Y02A50/475

Abstract: Disclosed are methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of at least one p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the at least one p38 MAPK by the compound. Also disclosed are derivatives of pirfenidone. These derivatives can modulate a stress activated protein kinase (SAPK) system.

Abstract translation: 公开了用活性化合物调节应激活化蛋白激酶（SAPK）系统的方法，其中活性化合物表现出低的抑制至少一种p38MAPK的能力; 并且其中所述接触以对所述化合物抑制至少一种p38MAPK的低百分比抑制浓度的SAPK-调节浓度进行。 还公开了吡非尼酮的衍生物。 这些衍生物可以调节应激活化蛋白激酶（SAPK）系统。

公开(公告)号：US20090148407A1

公开(公告)日：2009-06-11

申请号：US11996902

申请日：2006-07-17

Applicant: Lawrence M. Blatt ,  Scott D. Seiwert ,  Steven W. Andrews ,  Pierre Martin ,  Andreas Schumacher ,  Bradley Barnett ,  C. Todd Eary ,  Robert Kaus ,  Timothy Kercher ,  Weidong Liu ,  Michael Lyon ,  Paul Nichols ,  Bin Wang ,  Tarek Sammakia ,  April Kennedy ,  Yutong Jiang

Inventor： Lawrence M. Blatt ,  Scott D. Seiwert ,  Steven W. Andrews ,  Pierre Martin ,  Andreas Schumacher ,  Bradley Barnett ,  C. Todd Eary ,  Robert Kaus ,  Timothy Kercher ,  Weidong Liu ,  Michael Lyon ,  Paul Nichols ,  Bin Wang ,  Tarek Sammakia ,  April Kennedy ,  Yutong Jiang

IPC: A61K38/21 ,  C07K5/12 ,  A61K38/12 ,  C07D209/18 ,  C12N9/99 ,  A61K39/395

CPC classification number: C07K5/0806 ,  A61K38/00 ,  A61K38/1793 ,  A61K38/212 ,  A61K38/217 ,  A61K38/2292 ,  A61K38/55 ,  C07D471/04 ,  C07D487/04 ,  C07K5/0804 ,  A61K2300/00

Abstract: The embodiments provide compounds of the general Formulae (I) through general Formula (VIII), as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.

Abstract translation: 实施方案提供通式（I）至通式（VIII）的化合物，以及包含主题化合物的组合物，包括药物组合物。 实施方案还提供治疗方法，包括治疗丙型肝炎病毒感染的方法和治疗肝纤维化的方法，所述方法通常涉及向有需要的个体施用有效量的主题化合物或组合物。

公开(公告)号：US20090093533A1

公开(公告)日：2009-04-09

申请号：US12089895

申请日：2006-10-10

Applicant: Leonid Beigelman ,  Scott D. Seiwert ,  Lawrence Blatt ,  Steven Andrews ,  Julia Haas

Inventor： Leonid Beigelman ,  Scott D. Seiwert ,  Lawrence Blatt ,  Steven Andrews ,  Julia Haas

IPC: A61K31/407 ,  C07D245/00 ,  A61P31/12

CPC classification number: C07D487/04 ,  C07D471/04

Abstract: Macrocyclic compounds having the structures described herein are useful for inhibiting replication of the hepatitis C virus (HCV). In preferred embodiments, the compounds are active against both the NS3 protease and the NS3 helicase of HCV.

Abstract translation: 具有本文所述结构的大环化合物可用于抑制丙型肝炎病毒（HCV）的复制。 在优选的实施方案中，所述化合物对NS3蛋白酶和HCV的NS3解旋酶均有活性。