公开(公告)号：US09273014B2

公开(公告)日：2016-03-01

申请号：US14627573

申请日：2015-02-20

Applicant: Bristol-Myers Squibb Company

Inventor： Ashvinikumar V. Gavai ,  George V. DeLucca ,  Daniel O'Malley ,  Patrice Gill ,  Claude A. Quesnelle ,  Brian E. Fink ,  Yufen Zhao ,  Francis Y. Lee

IPC: A61K38/00 ,  A61K47/00 ,  C07D243/24 ,  A61K31/5513 ,  A61K31/573 ,  A61K31/675 ,  A61K38/05 ,  A61K45/06 ,  C07D401/04 ,  C07F9/645 ,  C07K5/062 ,  C07D243/18 ,  C07D243/26 ,  C07F9/12 ,  A61K9/00 ,  A61K9/08 ,  A61K31/138 ,  A61K31/337 ,  A61K31/506 ,  A61K31/555 ,  C07F7/18 ,  C07F9/38 ,  A61K9/48 ,  A61K47/48

CPC classification number: C07D243/24 ,  A61K9/0019 ,  A61K9/0095 ,  A61K9/08 ,  A61K9/4866 ,  A61K31/138 ,  A61K31/337 ,  A61K31/506 ,  A61K31/5513 ,  A61K31/555 ,  A61K31/573 ,  A61K31/675 ,  A61K45/06 ,  A61K47/64 ,  C07D243/18 ,  C07D243/26 ,  C07D401/04 ,  C07F7/1804 ,  C07F9/12 ,  C07F9/38 ,  C07F9/645 ,  A61K2300/00

Abstract: Disclosed are compounds of Formula (I) and/or salts thereof: wherein R1 is —CH2CH2CF3; R2 is —CH2CH2CF3 or —CH2CH2CH2CF3; R3 is H, —CH3, or Rx; R4 is H or Ry; Ring A is phenyl or pyridinyl; and Rx, Ry, Ra, Rb, y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer; or as prodrugs of such compounds.

公开(公告)号：US20150065465A1

公开(公告)日：2015-03-05

申请号：US14532218

申请日：2014-11-04

Applicant: Bristol-Myers Squibb Company

Inventor： Ashok Vinayak Purandare ,  Brian E. Fink ,  Ashvinikumar V. Gavai ,  Walter Lewis Johnson ,  Amy C. Hart ,  Liqi He ,  Tram N. Huynh ,  Jennifer Inghrim ,  Harold Mastalerz ,  Xiaopeng Sang ,  Christine M. Tarby ,  Honghe Wan ,  Wayne Vaccaro ,  Guifen Zhang ,  Yufen Zhao ,  Kurt Zimmermann

IPC: C07D487/04 ,  A61K45/06 ,  A61K31/541 ,  C07D487/08 ,  A61K31/5383 ,  C07D519/00 ,  A61K31/55 ,  A61K31/5377 ,  C07F9/6561 ,  A61K31/675 ,  A61K31/53 ,  A61K31/551

CPC classification number: C07D487/04 ,  A61K31/53 ,  A61K31/5377 ,  A61K31/5383 ,  A61K31/541 ,  A61K31/55 ,  A61K31/551 ,  A61K31/675 ,  A61K45/06 ,  C07D471/10 ,  C07D487/08 ,  C07D487/10 ,  C07D487/22 ,  C07D498/04 ,  C07D519/00 ,  C07F7/1804 ,  C07F9/6521 ,  C07F9/6561 ,  C07F9/65616

Abstract: The invention provides compounds of Formula (I) and pharmaceutically acceptable salts thereof. The Formula (I) imidazotriazines inhibit protein kinase activity thereby making them useful as anticancer agents.

Abstract translation: 本发明提供式（I）化合物及其药学上可接受的盐。 式（I）咪唑三嗪抑制蛋白激酶活性，从而使它们用作抗癌剂。

公开(公告)号：US20140087992A1

公开(公告)日：2014-03-27

申请号：US14032333

申请日：2013-09-20

Applicant: Bristol-Myers Squibb Company

Inventor： Ashvinikumar V. Gavai ,  George V. DeLucca ,  Daniel O'Malley ,  Patrice Gill ,  Claude A. Quesnelle ,  Brian E. Fink ,  Yufen Zhao ,  Francis Y. Lee

IPC: C07D243/24 ,  A61K45/06 ,  A61K31/573 ,  C07K5/062 ,  A61K31/675 ,  C07D401/04 ,  A61K38/05 ,  A61K31/5513 ,  C07F9/645

CPC classification number: C07D243/24 ,  A61K9/0019 ,  A61K9/0095 ,  A61K9/08 ,  A61K9/4866 ,  A61K31/138 ,  A61K31/337 ,  A61K31/506 ,  A61K31/5513 ,  A61K31/555 ,  A61K31/573 ,  A61K31/675 ,  A61K45/06 ,  A61K47/64 ,  C07D243/18 ,  C07D243/26 ,  C07D401/04 ,  C07F7/1804 ,  C07F9/12 ,  C07F9/38 ,  C07F9/645 ,  A61K2300/00

Abstract: Disclosed are compounds of Formula (I) and/or salts thereof: wherein R1 is —CH2CH2CF3; R2 is —CH2CH2CF3 or —CH2CH2CH2CF3; R3 is H, —CH3, or Rx; R4 is H or Ry; Ring A is phenyl or pyridinyl; and Rx, Ry, Ra, Rb, y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer; or as prodrugs of such compounds.

Abstract translation: 公开了式（I）和/或其盐的化合物：其中R 1是-CH 2 CH 2 CF 3; R2是-CH2CH2CF3或-CH2CH2CH2CF3; R3是H，-CH3或Rx; R4是H或Ry; 环A是苯基或吡啶基; 并且Rx，Ry，Ra，Rb，y和z在本文中定义。 还公开了使用这些化合物抑制Notch受体的方法，以及包含这些化合物的药物组合物。 这些化合物可用于治疗，预防或减缓各种治疗领域（例如癌症）中疾病或病症的发展; 或作为这些化合物的前药。

公开(公告)号：US11339185B2

公开(公告)日：2022-05-24

申请号：US16683667

申请日：2019-11-14

Applicant: Bristol-Myers Squibb Company

Inventor： Brian E. Fink ,  Dharmpal S. Dodd ,  Steven J. Walker ,  Libing Chen ,  Yufen Zhao ,  Zheming Ruan ,  Lan-Ying Qin ,  Peter Kinam Park ,  Muthoni G. Kamau ,  Lalgudi S. Harikrishnan

IPC: C07H19/213 ,  A61P35/00 ,  C07H21/02 ,  C07H21/00 ,  C07K16/28

Abstract: The present invention is directed to compounds of the formulae I, II and III as shown below wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.

公开(公告)号：US20210253624A1

公开(公告)日：2021-08-19

申请号：US16849091

申请日：2018-10-16

Applicant: Bristol-Myers Squibb Company

Inventor： Brian E. FINK ,  Yufen Zhao ,  Libing Chen ,  Audris Huang

IPC: C07H21/02 ,  C07K16/28 ,  A61K45/06

Abstract: The present invention is directed to compounds of the formula wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.

公开(公告)号：US10744150B2

公开(公告)日：2020-08-18

申请号：US16047071

申请日：2018-07-27

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Brian E. Fink ,  Dharmpal S. Dodd ,  Lan-ying Qin ,  Zheming Ruan ,  Yufen Zhao ,  Lalgudi S. Harikrishnan ,  Muthoni G. Kamau ,  Steven J. Walker

IPC: C07H19/20 ,  C07H19/23 ,  C07H19/207 ,  C07H19/14 ,  C07H21/04 ,  A61K31/7084 ,  A61P35/02 ,  A61P35/00 ,  A61K45/06

Abstract: The present invention is directed to compounds of the formulae I, II and III as shown below wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.

公开(公告)号：US09708316B2

公开(公告)日：2017-07-18

申请号：US14977709

申请日：2015-12-22

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Brian E. Fink ,  Yufen Zhao ,  Robert M. Borzilleri ,  Liping Zhang ,  Kyoung S. Kim ,  Muthoni G. Kamau ,  Andrew J. Tebben ,  Yong Zhang ,  Andrew F. Donnell

IPC: A61K31/4709 ,  A61K31/501 ,  C07D487/04 ,  C07D471/04 ,  A61K31/5377 ,  A61K31/437 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/541

CPC classification number: C07D471/04 ,  A61K31/437 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/501 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  C07D487/04 ,  Y02P20/582

Abstract: The invention relates generally to compounds that modulate the activity of TGFβR-1 and TGFβR-2, pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.

公开(公告)号：US09427442B2

公开(公告)日：2016-08-30

申请号：US14429958

申请日：2013-09-20

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Yufen Zhao ,  Ashvinikumar V. Gavai ,  Patrice Gill ,  Soong-Hoon Kim ,  Brian E. Fink ,  Libing Chen ,  Mark G. Saulnier ,  Wen-Ching Han

IPC: C07D243/24 ,  A61K31/5513 ,  A61K45/06

CPC classification number: A61K31/5513 ,  A61K31/138 ,  A61K31/337 ,  A61K31/506 ,  A61K31/555 ,  A61K45/06 ,  C07D243/18 ,  C07D243/24 ,  C07D243/26 ,  A61K2300/00

Abstract: Disclosed are compounds of Formula (I): (Formula (I)) wherein: R1 is —CH2CH2CF3; R2 is —CH2CH2CH2F, —CH2CF2CH3, —CH2CH2CF3, —CH2CH(CH3)CF3, —CH2CH2CF2CH3, (Formulae (II), (III), (IV), (V) or (VI): R3 is H or —CH3; Ring A is phenyl or pyridinyl; and Rx, Ry, Ra, Rb, y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer.

Abstract translation: 公开了式（I）的化合物：（式（I））其中：R 1是-CH 2 CH 2 CF 3; R2是-CH2CH2CH2F，-CH2CF2CH3，-CH2CH2CF3，-CH2CH（CH3）CF3，-CH2CH2CF2CH3，（式（Ⅱ），（Ⅲ），（Ⅳ），（Ⅴ）或（Ⅵ）：R3是H或-CH3; 环A是苯基或吡啶基; Rx，Ry，Ra，Rb，y和z在本文中定义。还公开了使用这些化合物抑制Notch受体的方法，以及包含这些化合物的药物组合物，这些化合物可用于 治疗，预防或减缓各种治疗领域（例如癌症）中的疾病或病症的发展。

公开(公告)号：US20150231152A1

公开(公告)日：2015-08-20

申请号：US14429958

申请日：2013-09-20

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Yufen Zhao ,  Ashvinikumar V. Gavai ,  Patrice Gill ,  Soong-Hoon Kim ,  Brian E. Fink ,  Libing Chen ,  Mark G. Saulnier ,  Wen-Ching Han

IPC: A61K31/5513 ,  A61K45/06 ,  C07D243/24

CPC classification number: A61K31/5513 ,  A61K31/138 ,  A61K31/337 ,  A61K31/506 ,  A61K31/555 ,  A61K45/06 ,  C07D243/18 ,  C07D243/24 ,  C07D243/26 ,  A61K2300/00

Abstract: Disclosed are compounds of Formula (I): (Formula (I)) wherein: R1 is —CH2CH2CF3; R2 is —CH2CH2CH2F, —CH2CF2CH3, —CH2CH2CF3, —CH2CH(CH3)CF3, —CH2CH2CF2CH3, (Formulae (II), (III), (IV), (V) or (VI): R3 is H or —CH3; Ring A is phenyl or pyridinyl; and Rx, Ry, Ra, Rb, y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer.

Abstract translation: 公开了式（I）的化合物：（式（I））其中：R 1是-CH 2 CH 2 CF 3; R2是-CH2CH2CH2F，-CH2CF2CH3，-CH2CH2CF3，-CH2CH（CH3）CF3，-CH2CH2CF2CH3，（式（Ⅱ），（Ⅲ），（Ⅳ），（Ⅴ）或（Ⅵ）：R3是H或-CH3; 环A是苯基或吡啶基; Rx，Ry，Ra，Rb，y和z在本文中定义。还公开了使用这些化合物抑制Notch受体的方法，以及包含这些化合物的药物组合物，这些化合物可用于 治疗，预防或减缓各种治疗领域（例如癌症）中的疾病或病症的发展。

公开(公告)号：US08999918B2

公开(公告)日：2015-04-07

申请号：US14032333

申请日：2013-09-20

Applicant: Bristol-Myers Squibb Company

Inventor： Ashvinikumar V. Gavai ,  George V. DeLucca ,  Daniel O'Malley ,  Patrice Gill ,  Claude A. Quesnelle ,  Brian E. Fink ,  Yufen Zhao ,  Francis Y. Lee

IPC: A61K38/00 ,  A61K47/00 ,  C07D243/24 ,  A61K31/5513 ,  A61K31/573 ,  A61K31/675 ,  A61K38/05 ,  A61K45/06 ,  C07D401/04 ,  C07F9/645 ,  C07K5/062 ,  C07D243/18 ,  C07D243/26 ,  C07F9/12 ,  A61K9/00 ,  A61K9/08 ,  A61K31/138 ,  A61K31/337 ,  A61K31/506 ,  A61K31/555 ,  A61K9/48 ,  A61K47/48

CPC classification number: C07D243/24 ,  A61K9/0019 ,  A61K9/0095 ,  A61K9/08 ,  A61K9/4866 ,  A61K31/138 ,  A61K31/337 ,  A61K31/506 ,  A61K31/5513 ,  A61K31/555 ,  A61K31/573 ,  A61K31/675 ,  A61K45/06 ,  A61K47/64 ,  C07D243/18 ,  C07D243/26 ,  C07D401/04 ,  C07F7/1804 ,  C07F9/12 ,  C07F9/38 ,  C07F9/645 ,  A61K2300/00

Abstract: Disclosed are compounds of Formula (I) and/or salts thereof: wherein R1 is —CH2CH2CF3; R2 is —CH2CH2CF3 or —CH2CH2CH2CF3; R3 is H, —CH3, or Rx; R4 is H or Ry; Ring A is phenyl or pyridinyl; and Rx, Ry, Ra, Rb, y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer; or as prodrugs of such compounds.

Abstract translation: 公开了式（I）和/或其盐的化合物：其中R 1是-CH 2 CH 2 CF 3; R2是-CH2CH2CF3或-CH2CH2CH2CF3; R3是H，-CH3或Rx; R4是H或Ry; 环A是苯基或吡啶基; 并且Rx，Ry，Ra，Rb，y和z在本文中定义。 还公开了使用这些化合物抑制Notch受体的方法，以及包含这些化合物的药物组合物。 这些化合物可用于治疗，预防或减缓各种治疗领域（例如癌症）中的疾病或病症的进展; 或作为这些化合物的前药。