公开(公告)号：US10010536B2

公开(公告)日：2018-07-03

申请号：US15387537

申请日：2016-12-21

Applicant: InterMune, Inc.

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

IPC: A61K31/4412 ,  A61K31/44 ,  A61K31/444

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.

公开(公告)号：US20170095462A1

公开(公告)日：2017-04-06

申请号：US15387537

申请日：2016-12-21

Applicant: InterMune, Inc.

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

IPC: A61K31/4412 ,  A61K31/444 ,  A61K31/44

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.

公开(公告)号：US09527816B2

公开(公告)日：2016-12-27

申请号：US14263787

申请日：2014-04-28

Applicant: InterMune, Inc.

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

IPC: A61K31/44 ,  A61K31/4412 ,  C07D213/26 ,  C07D213/63 ,  C07D213/16 ,  C07D213/64 ,  C07D215/227 ,  A61K31/4704 ,  A61K31/7052 ,  A61K31/45 ,  C07D213/69 ,  C07H15/26

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.

公开(公告)号：US20140242159A1

公开(公告)日：2014-08-28

申请号：US14271720

申请日：2014-05-07

Applicant: INTERMUNE, INC.

Inventor： Ramachandran Radhakrishnan ,  Ronald Vladyka ,  Kenneth Sultzbaugh

IPC: A61K9/48 ,  A61K31/4418

CPC classification number: A61K31/4418 ,  A61K9/4841 ,  A61K9/4858 ,  A61K9/4866 ,  A61K31/4412 ,  Y02A50/411

Abstract: A capsule formulation of pirfenidone is provided that includes pharmaceutically acceptable excipients. In one embodiment, this capsule formulation is capable of sustaining desirable pharmacokinetic responses in a patient. Further provided are methods of treating fibrotic conditions and other cytokine-mediated disorders by administering pirfenidone capsules of such formulation to a patient in need.

Abstract translation: 提供吡非尼酮的胶囊制剂，其包括药学上可接受的赋形剂。 在一个实施方案中，该胶囊制剂能够在患者体内维持所需的药代动力学反应。 还提供了通过将这种制剂的吡非尼酮胶囊给予需要的患者来治疗纤维化病症和其它细胞因子介导的病症的方法。

公开(公告)号：US20150065720A1

公开(公告)日：2015-03-05

申请号：US14538426

申请日：2014-11-11

Applicant: INTERMUNE, INC.

Inventor： Sabine M. Pyles ,  Michael Cyr ,  Ramachandran Radhakrishnan

IPC: C07D213/64

CPC classification number: C07D213/64 ,  A61K31/4412

Abstract: A process for synthesizing pirfenidone from bromobenzene having less than about 0.15% by weight dibromobenze is disclosed. Also disclosed are processes of synthesizing pirfenidone without using ethyl acetate or n-butanol, and pirfenidone having controlled levels of ethyl acetate, n-butanol, di(5-methyl-2-pyridinone)benzenes, and other impurities having specified retention times. Also disclosed are formulated dosage forms including the disclosed pirfenidone.

Abstract translation: 公开了一种从小于约0.15％（重量）二溴苯的溴苯合成吡非尼酮的方法。 还公开了在不使用乙酸乙酯或正丁醇的情况下合成吡非尼酮的方法，以及具有受控含量的乙酸乙酯，正丁醇，二（5-甲基-2-吡啶酮）苯和具有特定保留时间的其它杂质的吡非尼酮。 还公开了包括所公开的吡非尼酮的配制剂型。

公开(公告)号：US20150368200A1

公开(公告)日：2015-12-24

申请号：US14830999

申请日：2015-08-20

Applicant: INTERMUNE, INC.

Inventor： Sabine M. Pyles ,  Michael Cyr ,  Ramachandran Radhakrishnan

IPC: C07D213/64

CPC classification number: C07D213/64 ,  A61K31/4412

Abstract: A process for synthesizing pirfenidone from bromobenzene having less than about 0.15% by weight dibromobenze is disclosed. Also disclosed are processes of synthesizing pirfenidone without using ethyl acetate or n-butanol, and pirfenidone having controlled levels of ethyl acetate, n-butanol, di(5-methyl-2-pyridinone)benzenes, and other impurities having specified retention times. Also disclosed are formulated dosage forms including the disclosed pirfenidone.

公开(公告)号：US20140221660A1

公开(公告)日：2014-08-07

申请号：US14247357

申请日：2014-04-08

Applicant: INTERMUNE, INC.

Inventor： Sabine M. Pyles ,  Michael Cyr ,  Ramachandran Radhakrishnan

IPC: C07D213/64

CPC classification number: C07D213/64 ,  A61K31/4412

Abstract: A process for synthesizing pirfenidone from bromobenzene having less than about 0.15% by weight dibromobenze is disclosed. Also disclosed are processes of synthesizing pirfenidone without using ethyl acetate or n-butanol, and pirfenidone having controlled levels of ethyl acetate, n-butanol, di(5-methyl-2-pyridinone)benzenes, and other impurities having specified retention times. Also disclosed are formulated dosage forms including the disclosed pirfenidone.

Abstract translation: 公开了一种从小于约0.15％（重量）二溴苯的溴苯合成吡非尼酮的方法。 还公开了在不使用乙酸乙酯或正丁醇的情况下合成吡非尼酮的方法，以及具有受控含量的乙酸乙酯，正丁醇，二（5-甲基-2-吡啶酮）苯和具有特定保留时间的其它杂质的吡非尼酮。 还公开了包括所公开的吡非尼酮的配制剂型。

公开(公告)号：US08753679B2

公开(公告)日：2014-06-17

申请号：US13776079

申请日：2013-02-25

Applicant: Intermune, Inc.

Inventor： Ramachandran Radhakrishnan ,  Ronald Vladyka ,  Kenneth Sultzbaugh

IPC: A61K9/48 ,  A61K31/44

CPC classification number: A61K9/4841 ,  A61K9/4858 ,  A61K9/4866 ,  A61K31/4412 ,  A61K31/4418 ,  Y02A50/411

Abstract: A capsule formulation of pirfenidone is provided that includes pharmaceutically acceptable excipients. In one embodiment, this capsule formulation is capable of sustaining desirable pharmacokinetic responses in a patient. Further provided are methods of treating fibrotic conditions and other cytokine-mediated disorders by administering pirfenidone capsules of such formulation to a patient in need.

Abstract translation: 提供吡非尼酮的胶囊制剂，其包括药学上可接受的赋形剂。 在一个实施方案中，该胶囊制剂能够在患者体内维持所需的药代动力学反应。 还提供了通过将这种制剂的吡非尼酮胶囊给予需要的患者来治疗纤维化病症和其它细胞因子介导的病症的方法。

公开(公告)号：US20140228310A1

公开(公告)日：2014-08-14

申请号：US14263787

申请日：2014-04-28

Applicant: InterMune, Inc.

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

IPC: C07D213/64 ,  C07D213/69 ,  C07D215/227 ,  C07H15/26

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：US20130345430A1

公开(公告)日：2013-12-26

申请号：US13947643

申请日：2013-07-22

Applicant: INTERMUNE, INC.

Inventor： Sabine M. Pyles ,  Michael Cyr ,  Ramachandran Radhakrishnan

IPC: C07D213/64

CPC classification number: C07D213/64 ,  A61K31/4412

Abstract: A process for synthesizing pirfenidone from bromobenzene having less than about 0.15% by weight dibromobenze is disclosed. Also disclosed are processes of synthesizing pirfenidone without using ethyl acetate or n-butanol, and pirfenidone having controlled levels of ethyl acetate, n-butanol, di(5-methyl-2-pyridinone)benzenes, and other impurities having specified retention times. Also disclosed are formulated dosage forms including the disclosed pirfenidone.